Prenatal Development of the Eye and Its Adnexa

8/13/2019 Prenatal Development of the Eye and Its Adnexa

1/71

Prenatal Development of the Eye and Its AdnexaCYNTHIA S. COOK, VICTORIA OZANICS and FREDERICK A.

JAKOBIEC

Main Menu Table Of Contents

Search

EARLY MORPHOGENESISLENS INDUCTION AND DIFFERENTIATION

CONNECTIVE TISSUE COATSSTRUCTURES OF THE AQUEOUS OUTFLOW PATHWAYS

UVEA

NEUROECTODERMAL LAYERSBRUCH'S MEMBRANE

OPTIC NERVE AND DISC

VITREOUS AND HYALOID SYSTEM

ADNEXACONCLUSIONS

ACKNOWLEDGMENTSREFERENCES

In this text, we attempt to provide an overview of ocular embryology bydescribing essential developmental events in a concise fashion. Fine

structural data on human and primate eye components have become available

since the appearance of standard publications on ocular embryology byMann,

1Barber,

2Dejean and coworkers,

3and Duke-Elder and associates.

41

These observations aid in reconfirming or reevaluating the functional

development of ocular structures as expressed by morphologic changes. Our

descriptions are based on mammalian tissues, including both humans andother species that serve to model human development. Comparisons have

demonstrated that the sequence of developmental events is similar across

species. Factors that must be taken into consideration when makinginterspecies comparisons include: duration of gestation; differences in

anatomic endpoint (such as the absence in other species of a macula,

Schlemm's canal, or Bowman's membrane); and when eyelid fusion breaks(during the sixth month of gestation in the human versus 2 weeks postnatally

in the mouse. Within the limits of these species variation, mice have proven

to be a valuable model in the study of normal and abnormal ocular

morphogenesis. In particular, the study of effects of acute exposure to

teratogens during development has provided valuable information about thespecific timing of events leading to malformations.

In development of the eye, as in other organs, the multiplication of cells as

well as directional change in shape, structure, and function of the cells

govern growth. Gene determination decides the direction in which a changecan occur, whereas the reciprocal demands of the individual cells or parts

determine how far that direction must be followed. Fundamentally, the
http://www.oculist.net/downaton502/prof/ebook/duanes/index.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/index.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/contents.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/contents.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#earhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#earhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#lenhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#lenhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#conhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#conhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#strhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#strhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#uvehttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#uvehttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#neuhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#neuhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#bruhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#bruhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#opthttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#opthttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#vithttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#vithttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#adnhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#adnhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#conchttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#conchttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#ackhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#ackhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#refhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#refhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r1http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r1http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r1http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r2http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r2http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r2http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r3http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r3http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r3http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r41http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r41http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r41http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r41http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r3http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r2http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r1http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#refhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#ackhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#conchttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#adnhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#vithttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#opthttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#bruhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#neuhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#uvehttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#strhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#conhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#lenhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#earhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/contents.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/index.html


2/71

process consists of these two activities: change in structure and shape due to

relatively different rates of growth and also change in structure and function

due to differentiation and functional specialization.

Induction of one ocular tissue by another and interrelations between these

developing tissues have been extensively reinvestigated in many laboratoriesusing various experimental techniques.

521One example is the lens, which

arises in direct response to induction by the optic vesicle. The developing

lens, in turn, promotes normal morphogenesis of neural ectodermal andmesenchymal elements in the eye. It has an inducing influence on corneal

differentiation and promotes vitreous growth. Moreover, a strong

organogenetic connection exists between lens and iris. The reciprocal

interactions between optic cup and lens bring about the functional adjustmentof the ocular axes.

Although the neural retina grows and differentiates independently of the

lens, the presence of the lens may influence the normal growth and change inshape of the pigment epithelium, choroid, and sclera. The pigment

epithelium, however, directs the deposition of the mesenchyme around it;

subsequently, all three layers grow in unison. The pigment epithelium alsodepends on the vitreous body for increase in its area.

Back to Top

EARLY MORPHOGENESIS

Although events occurring during the first few weeks after fertilization, before the appearance of

identifiable ocular primordia, may seem to have little significance to the clinicalophthalmologist, evidence indicates that abnormalities that originate during this period may be

responsible for many ocular malformations that occur in humans.

Gastrulation (formation of the mesodermal germ layer) occurs early in gestation (day 7 in mice,day 20 in humans). The primitive streak forms as a longitudinal groove within the epiblast

(future ectoderm) of the bilaminar embryonic disc. Epiblast cells migrate medially toward theprimitive streak where they invaginate to form the mesodermal layer (Fig. 1). This forms the

classic three germ layers: ectoderm, mesoderm, and endoderm. Gastrulation progresses in a

cranial to caudal direction. Concurrently, cranial surface ectoderm proliferates forming bilateral

elevations called neural folds (Fig. 2). Columnar surface ectoderm in this area now becomes

neural ectoderm.
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r5http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r5http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r5http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r5http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r5http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/001f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/001f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/001f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/002f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/002f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/002f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/002f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/001f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r5


3/71

Fig. 1. A.Drawing of a 17-day-old embryo in gastrulationstage, dorsal view, with the amnion removed. B.Cross-

section of a 17-day-old embryo through the primitive

streak. The primitive streak represents invagination ofepiblast cells between the epiblast and hypoblast layers.

Note that the epiblast cells filling the middle area formthe mesodermal layer. C.Cross-section of the embryo atthe end of the third week showing the three definitive

germ layers: ectoderm, mesoderm, and endoderm. (Cook CS, Sulik KK, Wright KW:

Embryology. In Wright KW [ed]: Pediatric Ophthalmology and Strabismus, pp 343. St Louis:

Mosby, 1995.

Fig. 2. A.Drawing of dorsal view of a

human embryo at 19 to 20 days'

gestation. The neural plate transforms

into two neural folds on each side ofthe neural groove. The neural groove

in the middle of the embryo isshaded

to represent neural ectoderm; the

unshadedsurface of the embryo issurface ectoderm. B.Cross-section of same embryo through the neural plate. Ectoderm in the

area of the neural groove (shaded cells) has differentiated into neural ectoderm, whereas the

ectoderm on each side of the neural groove is surface ectoderm (clear white cells) (Cook CS,Sulik KK, Wright KW: Embryology. In Wright KW (ed): Pediatric Ophthalmology and

Strabismus pp 343. St Louis: Mosby, 1995.)

Experimental studies in mice using acute exposure to teratogens have demonstrated the

significance of the period of gastrulation to later ocular development. Exposure to ethanol orretinoic acid during a short period equivalent to the third week of human gestation causes

primary damage to the forebrain neural ectoderm.2224

This results in a spectrum ofmalformations including microphthalmia, anterior segment dysgenesis (Peters' anomaly), iris and

optic nerve colobomas, and persistent hyperplastic primary vitreous.25,26

As the neural folds elevate and approach each other (neurulation), a specialized population of

mesenchymal cells, the neural crest, emigrates from the neural ectoderm at its junction with the

surface ectoderm. In the development of the eye, the neural ectoderm(deriving from the neuralplate and neural folds), thesurface ectoderm, the neural crest, and, to a lesser extent, the

mesodermare of importance (Table 1).

TABLE 1. Embryonic Origins of Ocular Tissues

Neural ectoderm (optic cup)

Neural retina
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r22http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r22http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r22http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r22http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r22http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r25http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r25http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r26http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r26http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r26http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#t1http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#t1http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#t1http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/002f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/001f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/002f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/001f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#t1http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r26http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r25http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r22


4/71

Retinal pigment epithelium

Pupillary sphincter and dilator muscles

Posterior iris epithelium

Ciliary body epitheliumOptic nerve

Neural crest (connective tissue)

Corneal endotheliumTrabecular meshwork

Stroma of cornea, iris, and ciliary body

Ciliary muscleChoroid and sclera

Perivascular connective tissue and smooth muscle cells

Meninges of optic nerve

Orbital cartilage and boneConnective tissue of the extrinsic ocular muscles

Secondary vitreous

Zonules

Surface ectoderm (epithelium)

Corneal and conjunctival epitheliumLens

Lacrimal gland

Eyelid epidermisEyelid cilia

Epithelium of adnexa glands

Epithelium of nasolacrimal duct

Mesoderm (muscle and vascular endothelium)

Extraocular muscle cells

Vascular endothelia

Schlemm's canal endothelium

Blood

The cranial neural crest contributes most of the connective tissues of the eye and its adnexal

structures.14,19,2741

The hyaluronic acid-rich extracellular matrix influences migration and
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r14http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r14http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r19http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r19http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r19http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r14


5/71

differentiation of the neural crest cells. This acellular matrix is secreted by the surface epithelium

as well as the neural crest cells and forms a space through which crest cells migrate. Fibronectin

secreted by the noncrest cells forms the limits of the mesenchymal migration. Interactions

between the migrating neural crest and the associated mesoderm appear to be essential fornormal crest differentiation. Many congenital malformations of the anterior segment and cornea

probably arise from derangements in the axial migration of ocular neural crest.

Experimental embryologic studies have shown that the mesoderm actually contributes little to

head and neck mesenchyme. The cranial correlates to the paired paraxial somites are called

somitomeres.Seven pairs of cranial somitomeres have been identified in the mouse .33,40,4251

In

the eye, the mesoderm contributes only to the striated extraocular muscles and vascular

endothelia. To these limited primary mesodermal elements come associated neural crest satellite

cells (surrounding the striated muscles) and pericytes (surrounding the vascular endothelium).Circulating blood elements originate from mesoderm. The term mesenchyme broadly refers to

any embryonic connective tissue and should not be confused with mesoderm. With respect to the

head and neck, most of this connective tissue derives from the cranial neural crest, with the

exceptions mentioned.

The optic primordium is a thickened zone in the differentiating central nervous system that forms

the neural folds of the early embryo. Some of the neuroepithelium composing the opticprimordium becomes the future optic cup and stalk; some cells may delaminate to contribute to

the neural crest.27

The optic sulcus or groove arises in the primordium at the time when the

neural folds are still open in the forebrain (8 to 15 somite pairs, approximately 2 to 3.5 mm)(Figs. 3and4A). With enlargement of the sulcus, the optic evaginations and, later, the optic pits

appear in the region of the future forebrain (seeFig. 4B). The portion of the evaginations

adjacent to the midbrain contacts the mesencephalic neural crest cells, which will form the

mesenchymal envelope isolating neural from surface ectoderm (seeFig. 4C).

Fig. 3. Drawing of 23-day-old embryo, dorsal view, showing partial fusion of

the neural folds. Brain vesicles have divided into three regions: forebrain,midbrain, and hindbrain. Facing surfaces of the forebrain are lined with neural

ectoderm (shaded cells), but the most of the embryo is now lined with surface

ectoderm (clear white) because the neural groove has closed. On the inside ofboth forebrain vesicles is the site of the optic sulci. (Cook CS, Sulik KK,

Wright KW: Embryology. In Wright KW [ed]: Pediatric Ophthalmology and

Strabismus, pp 343. St Louis: Mosby, 1995.)
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r33http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r33http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r40http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r40http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r42http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r42http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r42http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r42http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r42http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r42http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r40http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r33


6/71


7/71

Fig. 5. A.Drawing of a cross-section through forebrainand optic sulci of 24-day-old embryo. Note that the neural

tube is still open. The optic sulci are lined by neural

ectoderm (shaded cells), while the surface of the forebrainis covered with surface ectoderm (clear white cells). As

the optic sulci (neural ectoderm) evaginate toward thesurface ectoderm (hollow arrows), the edges of the brainvesicles move together to fuse, thus closing the neural

tube (solid arrows). B.Drawing of a cross-section

through a 26-day-old embryo at the level of the optic

vesicle. Note that neural tube is closed, the surfaceectoderm now lines the surface of the forebrain, and the

neural ectoderm is completely internalized. The surface

ectoderm cells overlying the optic vesicles enlarge to

form the early lens placode. (Cook CS, Sulik KK, WrightKW: Embryology. In Wright KW [ed]: Pediatric Ophthalmology and Strabismus, pp 343. St

Louis: Mosby, 1995.)

The optic vesicles become sheathed with cells of neural crest origin27

that, except for a small

region in the center of the bulge, separate them from the surface ectoderm (seeFig. 4E). The

future primordium of the retina is present before closure of the neural tube, when the neuralectoderm is still open to the amniotic cavity. The optic stalk is formed by a constriction of the

area between the vesicles and the future forebrain. At this time, all cells lining the inner surface

of the vesicle's cavity are ciliated, and its outer surface, as well as the inner aspect of the surface

ectoderm overlying it, is covered by a thin basal lamina.

The next event is invagination of the optic vesicles by differential growth and buckling to form

the optic cup (Figs. 6to9). The temporal and lower walls move inward against the upper andposterior walls. This process also involves the optic stalk so that the optic

(choroid/embryonic/retinal) fissure is formed where the two laterally growing edges of the cup

and stalk meet. Mesenchyme (primarily neural crest) penetrates immediately into the cup byfilling up the fissure.

Fig. 6. Drawing of a transection through a 28-day-old embryoshowing invaginating lens placode that is pushing into the optic

vesicle (arrows), thus creating the optic cup. Note the

orientation of the eyes 180 degrees from each other. This is also

illustrated inFigures 9BandC.(Cook CS, Sulik KK, WrightKW: Embryology. In Wright KW [ed]: Pediatric

Ophthalmology and Strabismus, pp 343. St Louis: Mosby,

1995.)
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/005f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/005f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r27


8/71

Fig. 7. Drawing shows formation of the lens vesicle andoptic cup. Note that the optic fissure is present because

the optic cup is not fused inferiorly. Mesenchyme (M)

surrounds the invaginating lens vesicle. Note that theoptic cup and optic stalk are made of neural ectoderm.

(Cook CS, Sulik KK, Wright KW: Embryology. InWright KW [ed]: Pediatric Ophthalmology andStrabismus, pp 343. St Louis: Mosby, 1995.)

Fig. 8. Drawing of cross-section at approximately 5 weeks'gestation through optic cup and optic fissure. The lens vesicle isseparated from the surface ectoderm. Mesenchyme (M)

surrounds the developing lens vesicle and the hyaloid artery is

seen with the optic fissure. See alsoFigure 9F.(Cook CS, Sulik

KK, Wright KW: Embryology. In Wright KW [ed]: PediatricOphthalmology and Strabismus, pp 343. St Louis: Mosby,

1995.)

Fig. 9. Invagination

of the optic cup andlens vesicle. Mouse

embryos areillustrated. A.Embryo of somite

pairs (fifth week in a

human). On external

examination, theinvaginating lensplacode can be seen

(arrow). Note its

position relative tothe maxillary (Mx)

and mandibular (Mn)prominences of the

first visceral arch ( 106). B.Embryo of the same age as inFigure 3A.Frontal fracture through

the lens placode (arrow) illustrates the associated thickening of the surface ectoderm (E).

Mesenchyme (M) of neural crest origin is present adjacent to the lens placode. Distal portion of

the optic vesicle thickens concurrently, as the precursor of the neural retina (NR), whereas theproximal optic vesicle becomes a shorter, cuboidal layer that is the anlage of the retinal
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/008f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/007f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/008f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/007f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/008f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/007f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/003f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.html


9/71

pigmented epithelium (PE). The cavity of the optic vesicle (V) becomes progressively smaller( 367). C.Epithelium of the lens placode continues to invaginate (L). There is an abrupt

transition between the thicker epithelium of the placode and the adjacent surface ectoderm,

which is not unlike the transition between the future neural retina (NR) and the futurepigmented epithelium (PE). (Periodic acid-Schiff's stain; 443) D.As the lens vesicle enlarges

during the eleventh day, the external opening, or lens pore (arrow), becomes progressivelysmaller. The lens epithelial cells at the posterior pole of the lens elongate to form the primarylens fibers (L). NR, anlage of the neural retina; PE, the anlage of the pigmented epithelium

(now a very short cuboidal layer) ( 300). E.External view of the lens pore (arrow) and its

relationship to the maxillary prominence (Mx)32 somite pairs ( 260). F.Frontal fracture

reveals the optic fissure (*) where the two sides of the invaginating optic cup meet. This formsan opening in the cup allowing access to the hyaloid artery (H), which ramifies around the

invaginating lens vesicle (L). The former cavity of the optic vesicle is obliterated except in the

marginal sinus (S), at the transition between the neural retina (NR) and the pigmented

epithelium. E, surface ectoderm ( 307).

The optic vesicle and optic stalk invaginate through differential growth and infolding. Localapical contraction

52and physiologic cell death

53have been identified during invagination. This

process progresses from inferior to superior so that the sides of the optic cup and stalk meet

inferiorly in the optic fissure. The two lips of the optic fissure meet and initially fuse anterior to

the optic stalk with fusion progressing anteriorly and posteriorly. Failure of normal closure ofthis fissure may result in inferiorly located defects (colobomas) in the iris, choroid, or optic

nerve.

Closure of the optic cup through fusion of the optic fissure allows establishment of intraocular

pressure. Studies have demonstrated that, in the chick, the protein in the embryonic vitreous

humor is derived from plasma proteins entering the eye by diffusion out of permeable vessels in

the anterior segment.54After optic fissure closure, protein content in the vitreous decreases,possibly through dilution by aqueous humor produced by developing ciliary epithelium.

Table 2lists the chronologic sequence of ocular development and comparative body-eye

measurements in relationship to embryonic time intervals.

TABLE TWO. Revised Sequence of Human Ocular Development
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r52http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r52http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r53http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r53http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r54http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r54http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r54http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#t2http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#t2http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#t2http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r54http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r53http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r52


10/71

Mont

h

Week(s

)

Day(s

)

CR

Lengt

h

(mm)

Neuroectoderm

al Derivatives

Posterior iris

epithelium,

ciliary body

epithelium,

pupillary

muscles, neural

retina, retinal

pigment

epithelium

(RPE),

secondary

vitreous, and

optic nerve

Neural Crest

Derivatives

Corneal

endothelium,

stroma of

cornea, iris,

and ciliary

body, ciliary

muscle,

trabecular

meshwork,

choroid,

sclera,

secondary

vitreous, and

orbit

Surface

Ectoderm

Derivatives

Corneal

and

conjunctiva

l

epithelium,

lens, eyelid

epidermis,

eyelid cilia

and glands,

lacrimal

gland,

nasolacrim

al duct

Mesoderma

l

Derivatives

Endotheliu

m of

Schlemm's

canal,

vascular

(hyaloid,

tunica

vascula

lentis

(TVL)

endotheliu

m,

extraocular

muscles

1 3 20 12 Neural platethickens

Gastrulation(formation

of

mesoderm)

4 22 23.5 Optic sulci

present in

forebrain

24 23 Neural tube

closed Opticstalk formed

25 34 Optic sulci

converted into

optic vesicles

Mesenchyme

surrounds optic

vesicle

27 45 Optic vesicle

contacts surface

ectoderm

Lens

placode

begins to

thicken

Eyelidterritory

determined

2 5 29 57 Optic vesicle

begins toinvaginate

forming optic

cup with opticfissure

Lens pit

forms aslens placode

invaginates

Cord ofectoderm

Hyaloid

artery entersthrough the

optic fissure


11/71

buried by

maxillaryprocesses to

later form

nasolacrima

l duct

33 79 Optic fissure

closed Pigment

in outer layer ofoptic cup (future

RPE)

Oculomotor

nerve presentTrochlear and

abducens nerves

appear

Lens pit

closed

forminglens vesicle

surrounded

by intact

basementmembrane

(lens

capsule)Corneal

epithelium

formed

6 37 811 Ciliary ganglionpresent

Choriocapillarisformed around

the optic cup

Primarylens fibers

fill lens

vesicle

formingembryonal

nucleus

40 11

14

Retina consists

of: externallimiting

membrane (with

zonulaadherens),

proliferative

zone, primitive

zone, marginalzone, and

internal limiting

membrane

Corneal

endotheliumformed

Secondary

lens fibersform Lid

folds

present

7 4245

1317

Retina consistsof: inner

neuroblastic

layer, transient

fiber layer of


12/71


13/71

developmen

t

11 7177

505 Inner plexiform

layer formed

Cilia withindeveloping innersegments

Conjunctiva

l goblet

cells present

1214 78

90

60

80

Outer plexiform

layer separates

horizontal andbipolar nuclei

from

rudimentary

rods and conesSynapses

develop betweenphotoreceptors,ganglion cells,

and bipolar cells

in central retinaFirst indication

of ciliary

processes

Lamina

cribrosa

formationbegins

Marginal

bundle of

Drualt/vitreousbase present

Glands of

Moll,

meibomianglands

present

Rectus

muscle

tendons fusewith sclera

Branches of

ophthalmic

arteryaccompany

hyaloidartery Iridalmajor

arterial

circleformed

4 15 90

100

Orbital axis 105 Ciliary muscle

appears

Glands of

Zeisspresent

16 100

120

Mitosis ceases in

the neural retina

Corneal

endothelium

exhibitszonulae

occludentes

Aqueous humorformation

begins

Regression of

corneal

endotheliumcovering

iridocornealangle recess

Schlemm's

canal

presentTunica

vasculosa

lentis beginsto atrophy

120

130

Pupillary

sphincter

develops

Scleral spur

developing

Bowman's

Short

eyelashes

appear

Hyaloid

artery

begins to


14/71

membrane

present

atrophy to

the disc;branches of

the central

retinal artery

form

5 120

180

Outer segments

formation begins

Differentiationof macula begins

Layers of the

choroid

completeCloquet's canal

formed

6 175

230

Pupillary dilator

muscle develops

Ora serratadistinct nasally

Pupillary

membrane

begins toatrophy axially

Capsulohyaloidal ligamentpresent

Eyelids

begin to

open, lightperception

7 220

260

Iris

pigmentation

present Laminacribrosa mature

Myelination

begins at the

chiasm andprogresses to

the lamina

cribrosa

8 240280

Retinal layersdeveloped

except at macula

Regression ofpupillary

membrane

nearly complete

Retinalvessels

reach the

ora serrata

9term

310350

Orbital axis 71 Lacrimalduct

canalized

Back to Top

LENS INDUCTION AND DIFFERENTIATION

As the optic vesicles enlarges, it contacts the overlying surface ectoderm.The first manifestation of lens induction is the appearance of a disc-shaped
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#top


15/71

thickening of surface epithelial cells (27 days' gestation) (seeFigs. 5B,6,and

9AandB). A tight, extracellular matrix-mediated adhesion between the optic

vesicle and the surface ectoderm has been described. This anchoring effect

on the mitotically active ectoderm results in cell crowding and elongationand formation of a thickened placode. Adhesion between the optic vesicle

and lens placode serves to ensure alignment of the lens and retina in thevisual axis. Although adhesion between the optic vesicle and surfaceectoderm exists, the respective basement membranes remain separate and

intact throughout the contact period (seeFig. 4F). Inductors for lens

formation may act on the regulation of structural genes, or they may actdirectly on the cell cytoplasm. Lens induction thus may involve transfer of

inductor substances from the optic cup to the surface cells across both

basement membranes. Invagination of the lens placode (29 days) is

accomplished by a synergistic elongation of the placode cells withcontraction of their apical cytoplasm and terminal bar system (seeFigs. 7

and9C). The processes of differentiation into a lens pit, cup, and then a

vesicle have been studied in detail.6171

As the lens placode invaginates, it forms a hollow vesicle (seeFigs. 8and

9D). The area of contact of the optic vesicle and the surface ectodermdetermines the size of the lens vesicle, orbit, and palpebral fissure. The lens

separates from the surface epithelium at about 33 days' gestation (7 to 9 mm;

see Fig. 9D). The vesicle consists of a single layer of cells, covered by abasal lamina. Through appositional growth to its epithelial surface, the basal

lamina acquires more layers that become the lens capsule. At first, the

posterior capsule is more prominent than the anterior; the outer layers may

have components from the mesodermal tissues forming the hyaloid vascular

network.72

A zone of necrosis develops, displacing the lens placode from thesurface ectoderm (seeFig. 9EandF). The process of lens vesicle detachment

is accompanied by active migration of epithelial cells out of thekeratolenticular stalk, cellular necrosis, and basement membrane

breakdown.73,74

Cup formation is achieved by contraction of the apical

filaments. The process of induction is thus localized.

PRIMARY LENS FIBERS

The hollow lens vesicle consists of a single layer of epithelial cells with cell

apices directed toward the center. Following detachment from the surface

ectoderm, the lens vesicle is surrounded by a basal lamina, the future lenscapsule. The cells lengthen (Figs. 10and11A)until the lumen of the vesicleis filled (45 days, 17 mm). These constitute the primary lens fibers. The

apical ends of the newly formed fibers become firmly attached to the apical

surface of the anterior lens epithelium.
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/005f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/005f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/005f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/005f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/007f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/007f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/007f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/008f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/008f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/008f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r72http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r72http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r72http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r73http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r73http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r74http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r74http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r74http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/010f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/010f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/010f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/010f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r74http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r73http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r72http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/008f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/007f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/004f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/009f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/006f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/005f.html


16/71

Fig. 10. Drawing showing formation ofthe embryonic lens nucleus and primary

lens fibers at approximately 6 weeks.

Neural crest mesenchyme (M) surroundsthe optic cup. The posterior lens

epithelial cells (located nearest thedeveloping retina) elongate to form theprimary lens fibers. The anterior

epithelium remains cuboidal and becomes the anterior epithelium in the

adult. The optic fissure is now closed. The hyaloid vessels are seen between

the lens and retina. (Cook CS, Sulik KK, Wright KW: Embryology. InWright KW [ed]: Pediatric Ophthalmology and Strabismus, pp 343. St

Louis: Mosby, 1995.)

Fig.

11.Form

ation

of the

lensfibers

;

earlyretina

l

differ

entiation.

A.Elon

gation of the lens fibers located nearest to the neural retina forms the

embryonal lens nucleus (L) and obliterates the lens vesicle cavity. The

endothelial cells that form the tunica vasculosa lentis are indicated byarrows ( 392). B.Formation of the secondary lens fibers is apparent as

elongation of the epithelial cells at the equatorial lens bow. C, cornea; NR,

neural retina; L, lens ( 270). C.Electron micrograph evaluation of the

developing lens (L). LE, anterior lens epithelium, E, surface ectoderm (298). D.Corneal endothelium (open arrow) and stroma (C) are completely

formed but the anterior iridial stroma and iridocorneal angle (*) structures

are still immature and covered by the endothelium. The outer, pigmented

layer of the optic cup (O), which forms the pupillary sphincter and dilatormuscles, is in apposition to the cornea in the area of the future aqueous

outflow pathways (*). The arrowhead indicates the capillaries of the

anterior tunica vasculosa lentis. L, lens ( 407). Eand F.The retina hassegregated into an inner neuroblastic layer (IN) containing the primitive

ganglion cells the axons of which form the nerve fiber layer (arrow), and an
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/010f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/010f.html


17/71

outer neuroblastic layer (ON) containing the primordia of thephotoreceptors, retinal interneurons, and glial cells (E, 430; F, 316).

PE, retinal pigmented epithelium.

The retinal anlage promotes primary lens fiber formation in the adjacent lens

epithelial cells. Surgical rotation of the lens vesicle in the chick's eye by 180

degrees results in elongation of the lens epithelial cells nearest thepresumptive retina, regardless of the orientation of the transplanted lens.

56

The retina thus develops independently from the lens, while the lens appears

to rely on the retina for cytodifferentiation. This transformation of primarylens fibers is accompanied by ultrastructural changes in the nucleus and

cytoplasm, decreased numbers of organelles, and increased numbers of

fibrillar materials composed of the characteristic lens proteins.71

The

primitive lens filled with primary lens fibers forms the embryonal nucleus,visible in the adult. This portion of the lens lacks sutures.

SECONDARY LENS FIBERS

The cells nearest the corneal primordium remain cuboidal and become the

lens epithelium, which remains mitotic throughout life, giving rise to futurelens fiber cells. Production of the secondary lens fibers is initiated by

migration of the anterior epithelial cells toward the equator and their

elongation at various degrees with a shift in their nuclear distribution, thusresulting in the lens bow (Fig. 12B,C,andF,and13;seeFigs. 11BandC).

The basal ends of the fibers remain tightly attached to the basal lamina; their

apical ends extend anteriorly to the center, thus forming the anterior suture.

The tips of these secondary fibers are not yet tapered. A corresponding

increase in cell volume and decrease in intercellular space within the lensaccompany lens fiber elongation.

61The lens fibers exhibit surface

interdigitations. They extend around the primary fibers beneath the capsuleand meet in planes, the lens sutures, arranged essentially vertically to the

surface. The basic anatomy of the lens is established after the first layer of

secondary fibers has been placed (seventh week of gestation).75
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r56http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r56http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r56http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r71http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r71http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r71http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/013f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/013f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/013f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r75http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r75http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r75http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r75http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r61http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/011f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/013f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r71http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r56


18/71

Fig.12.

Form

ationof

thelensand

irido

corne

alangle

. A.

Ante

riorsegm

ent at8week

s'

gestation.

The

corne

al stroma (C) and endothelium have formed. The dense pupillary membrane(arrow) fills much of the space within the anterior chamber. L, lens ( 100).

B.Fractured lens at 7 weeks' gestation. Note embryonic nucleus (N) and

anterior lens epithelium (arrow) ( 102). C.Higher magnification of (B) toillustrate secondary lens fibers and lens bow ( 376). D.Longitudinal view

of lens fibers illustrating interdigitations ( 706). E.Cross-section of lens

fibers illustrating tightly apposed hexagonal arrangement ( 1012). F.Light

microscopic view of lens bow and close proximity of lens equator withanterior margin of optic cup. Note the hyaloid vasculature surrounding the

lens (arrows) ( 220). G.At 8 weeks' gestation, following removal of the

lens and the pupillary membrane, the anterior chamber can be visualized (103). H.Higher magnification of (G). The edge of the pupillary membrane

can be seen (arrow) as well as the anterior margin of the optic cup (O) and

the developing outflow pathways. The clefts visible in the limbal region

canalize to form Schlemm's canal. C, cornea ( 220). I.At 13 weeks'gestation, there are immature ciliary processes located in the region of the

future posterior iris (arrow). Differential growth with relative posterior

movement of the inner optic cup, results in the ultimate matureconformations coinciding with exposure of the trabecular meshwork as

described by Anderson ( 95). C, cornea; (B-E,courtesy of Dr. Kathy

Sulik.)
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.html


19/71

Fig. 13. Lens at 65 mm (12-week fetus) intransverse section. Posterior suture (arrow) extends

from the surface to the central, primary lens fibers

(location of the embryonic nucleus). The triangularanterior suture (thick arrow) is indicated by an

assembly of transversely cut fibers at the anteriorpole. Posterior vascular lens capsule is indicated byhollow arrow. The nucleated area is the location of

the secondary lens fibers. Lens bow (Lb) is formed by anteriorly migrating

nuclei of newly formed lens fibers. pm, vessels of the pupillary membrane;

V, vitreous ( 40).

LENS SUTURES

Succeeding generations of cells extend anteriorly and posteriorly from the

equator beneath the capsule. The anterior suture line is shaped like a Y that is

inverted in the posterior aspect. The posterior suture is formed when theposterior central cells lose their nuclei, become separated from their basal

lamina, and migrate inward.66

Curved lens fibers result, with the superficial

ones being the longest. Linear and triradiate sutures form, representingdifferent stages in lens development.

MATURATION

The shape of the lens and its orientation with respect to the optic axis

continually adjust to the developing eye. This is partly regulated by theneural retina and peripheral mesenchyme.

10Through the third month of

gestation, the anteroposterior diameter is greater than the equatorial. Mainlybecause of the continued generation of secondary fibers, the equatorialdiameter increases rapidly, thus making the lens more and more ellipsoid.

The lens, still somewhat spherical at birth, grows throughout life.

A general structural densification occurs progressively during maturation.

Fibrillar material is increased within the cytoplasm and cell organelles are

decreased. The successive parallel layers of interdigitating, elongated lensfibers become tightly apposed (seeFig. 12DandE). Deeper nuclei become

homogenous and dense. By the end of the third month, the innermost cells

have lost their nuclei and simultaneously show disintegration of the

chromatin and the ribosomes, leaving a finely filamentous cytoplasm.

Back to Top

CONNECTIVE TISSUE COATS

CORNEA

Among the many publications on the morphogenesis of the cornea (Fig. 14)
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r66http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r66http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r66http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r10http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r10http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r10http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/013f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/012f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r10http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r66


20/71

and the development of its constituents in various vertebrates, only a few can

be cited in this general review.

Fig.

14.

Schema

tic

diag

ramof

the

dev

eloping corneacentral region. A.At 39 days, the two-layered epitheliumrests on a basal lamina. It is separated from a two-to three-layered

endothelium by a narrow, cellular space. B.At 7 weeks, mesenchyme

from the periphery migrates into the space between epithelium andendothelium. It is the precursor of the future corneal stroma. C.The

mesenchyme (fibroblasts) is arranged in four to five incomplete layers by

7 weeks and a few collagen fibrils appear among them. D.By 3 months,the epithelium has 2 to 3 layers of cells and the stroma about 25 to 30 layers

of fibroblasts (keratoblasts) that are more regularly arranged in its posterior

half. There is a thin, uneven Descemet's membrane between the most

posterior keratoblasts and the monolayered endothelium. E.By midterm(4.5 months) some wing cells are forming above the basal epithelial cells

and an indefinite, acellular Bowman's membrane emerges beneath the basal

lamina. About one third of the anterior portion of the multilayered stroma

has its keratoblasts ina disorganized formation. Descemet's membrane iswell developed. F.At 7 months the cornea has its adult structure

established. A few mostly superficial keratoblasts are still randomly

oriented with respect to the corneal surface. The collagenous lamellae in therest of the stroma are in parallel array with only a few spaces in the matrix

lacking collagen fibrils. Breaks (near the bottom of Eand F) indicate that

the central portion of the stroma is not represented.

Epithelium

When the lens cup separates from the surface ectoderm in embryos at about

33 days' postfertilization (7 to 9 mm in length), development of the corneacan be said to have begun. The surface ectoderm becomes continuous

covering the optic cup and lens vesicle and later develops into the cornealepithelium.

Descemet's Membrane and Endothelium
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.html


21/71

During the next week, mesenchymal cells grow centrally between the basal

laminae of the lens and corneal epithelium (Fig. 15;see14A-C). Posterior to

the basal lamina of the corneal epithelium, the mesenchyme has produced a

double row of flattened cells, the future corneal endothelium (seeFig. 14A).

Fig. 15. Corneal epithelium (Ep) andmesenchymal cells (Me) beneath the

basal lamina are destined to form the

endothelium. Section is from a

monkey embryo at 34 days,comparable with that of a human at

approximately 5.5 weeks ( 480). Le,

lens.

Descemet's membrane first appears at 8 weeks as a patchy accumulationresembling basement membrane material.

91,92The patches become confluent

and thickened owing to the synthetic activity of the endothelial cells.Evidence of organization is seen early during the fourth month, when four or

five superimposed lamellae interspersed with collagen fibrils appear on the

stromal side of the endothelial basal lamina. The endothelium has zonulaeoccludentes at the cell apices by the middle of the fourth month of

development. Their appearance corresponds to the onset of aqueous humor

formation.

Stroma

Following formation of the corneal endothelium, mesenchyme (neural crest)

continues to migrate axially over the rim of the optic cup during the seventhweek (17 to 18 mm) (Fig. 16). At 8 weeks (18 to 22 mm), migratingmesenchymal cells from the periphery invade the space between epithelium

and endothelium. This mesenchyme, as well as that which will give rise to

the sclera and iris stroma, is of neural crest origin.30

The central portion ofthe future stroma is still acellular (seeFig. 14B). The endothelium merges

with the stratified cells at the periphery over the lips of the optic cup. This

mass of cells, in turn, is continuous with the cellular scleral condensation

extending to the equator of the globe. The developing keratocytes begin to

produce glycosaminoglycans.104
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/015f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/015f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/015f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r91http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r91http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r92http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r92http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r92http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/016f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/016f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/016f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r30http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r30http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r30http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r104http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r104http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r104http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/015f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r104http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r30http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/016f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r92http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r91http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/015f.html


22/71

Fig. 16. Embryo at 22 mm (approximately 7 weeks)showing relation of the anterior segment components (

260). The two arrowsindicate blood channels in the

mesenchyme around the rim of the cup. Peripheral part ofthe pupillary membrane running from the mesenchyme in

front of the optic cup (mes) to the anterior lens capsuleoutlines the incipient anterior chamber lying between itand the posterior surface of the cornea (hollow arrows).

Asterisk is placed at the peripheral limit of the anterior chamber. Curved

arrows point to capsula perilenticularis fibrosa. C, cornea; LE, lens

epithelium; V, primary vitreous; ov, tip of the neuroectodermal optic cup.

In the early 8-week-old embryo, about 22 mm in length, the mesenchymal

stroma consists centrally of five to eight rows of cells (Fig. 14C), within afibrillar matrix containing collagen. Nerves have been identified within the

corneal stroma and between epithelial cells at 3 months.105107

The most posterior layers of the corneal stroma are confluent peripherally

with a condensed band of mesenchyme that is gradually spreading backward

to enclose the eye. The mesenchyme destined to form the sclera is notdistinct from that which will form the four oculomotor muscles.

The cornea at 2 months (about 20 mm) consists of an epithelium of outersquamous and basal columnar cells. The middle polygonal or wing cells of

the adult do not appear until the fourth or fifth month. The stroma has about

15 layers of cells with rapidly developing collagen fibrils, most in the

posterior portion. At 3 months, the endothelium of the central area consists

of a single row of flattened cells that seem to rest on an interrupted basallamina, the first indication of a thin Descemet's membrane. With the

exception of Bowman's membrane, all corneal components are present (seeFig. 14D).

Bowman's Membrane

Arising relatively late in gestation (seeFig. 14EandF), Bowman'smembrane is observed by light microscopy during the fifth month, but

somewhat earlier by electron microscopy. It is always acellular, presumably

formed by the most anterior fibroblasts of the stroma, which move

posteriorly as Bowman's fibers and the ground substance are synthesize. Theepithelium may play a partial role in the local polymerization of the collagen

precursors presumably produced by the most anterior stromal fibroblasts.108

Transparency

Perhaps the most important and unique corneal characteristic is its
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r105http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r105http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r105http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r105http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r105http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r108http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r108http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r108http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/016f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r108http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r105http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/014f.html


23/71

transparency, which also develops during fetal life. The early embryonic and

fetal cornea is translucent rather than transparent and is more hydrated than

in the adult.94

Condensation begins in the posterior stroma during fetal

maturation.95

At about the time that the most anterior stromal lamellae areformed, corneal transparency reaches adult quality. During this development,

the water content of the cornea is being reduced so that the adult level ofcorneal hydration is attained at the same time as transparency.

SCLERA

The sclera forms first anteriorly, by mesenchymal condensation at the limbus

near the future insertion of the rectus muscles and grows gradually

posteriorly. Fibrocytes are involved in the synthesis of the elastic foci in thesclera.

109In contrast, the cornea lacks elastic components.

Inspection of the sclera at 60 to 65 mm or 12 weeks reveals it as a

mesenchymal condensation that has reached the posterior pole of the eye andsurrounds the optic nerve. Some cells have entered among the optic nerve

fibers and are arranged transversely, forming the first stages of theconnective tissue lamina cribrosa. The scleral spur appears at 4 months as

circularly oriented fibers; at 5 months, it is visible behind the anterior

chamber. At this time the sclera is well differentiated all around the eye.

Although the corneal and scleral cells are derived from the same mass of

mesenchyme surrounding the anterior part of the optic cup, they behavedifferently when in their definitive position. Corneal fibroblasts form

collagen faster than the scleral cells and differ in the rate and amount of

noncollagenous protein that they synthesize.110

Back to Top

STRUCTURES OF THE AQUEOUS OUTFLOW PATHWAYS

IRIDOCORNEAL ANGLE

Light and scanning electron-microscopic studies reveal the anterior chamberangle of the human eye to have a continuous endothelial lining during the

third and fourth months (Figs. 17and18). The tissues in the angle later

differentiate into a loose reticulum with large enclosed spaces near the iris

and ciliary body; outside of this trabecular tissue, a tighter aggregation of

cells is oriented toward the sclera.111115With the growth of surroundingstructures, Schlemm's canal comes to lie at the level of the apex of the angle.

Descemet's membrane and the corneal endothelium still cover a portion of

the trabecular meshwork, but the endothelial lining of the chamber hasbecome discontinuous (Figs. 19and20). The loose reticular tissue of the

earlier stages now occurs only in the deepest part of the angle, where it has
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r94http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r94http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r94http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r95http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r95http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r95http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r109http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r109http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r109http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r110http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r110http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r110http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/018f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/018f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/018f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r111http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r111http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r111http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r111http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/019f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/019f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/019f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/019f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r111http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/018f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#tophttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r110http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r109http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r95http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/v7c002.html#r94


24/71

large intercellular spaces (seeFigs. 17Cand20).

Fig. 17. Schematic diagram of theprogressive deepening of the angle;

its relation to the neighboring tissues.

A.At 3 months, corneal endotheliumextends nearly to the angle recess: an

incipient Schlemm's canal

(arrowhead) and a more posterior

scleral spur condensation (hollowarrow) appear to its left. Pigment

epithelium of the forward growing

ectodermal optic is indented by blood

vessels. The secondary vitreous fibrilsrun parallel to its surface (arrow).

This is the faisceau isthmique or

marginal bundle of Druault. B.At 4months, the angle recess has deepened and the endothelial lining has

receded somewhat. There is a small aggregate of differentiating sphincter

muscle fibers near the tip of the optic cup. Arrowhead points to Schlemm'scanal. The condensed tissue just posterior to Schlemm's canal is the

developing scleral spur (hollow arrow). Arrow points to the developing

tertiary vitreous or zonular fibers. They originate from the nonpigmented

ciliary epithelium and pass at right angles through Druault's bundle towardthe lens capsule. C.The iris has grown and only its ciliary portion is

presented. The angle recess has deepened and is occupied by loose

connective tissue separated by many spaces. The dilator muscle of the iris

has reached its root, which is still thick.Arrowheadpoints to the majorarterial circle. D.Sphincter muscle is fully developed and is separated by

connective tissue septa into several groups of cells. The collarette is

represented as a surface stromal bulge containing two blood vessels (curvedhollow arrow). E.Schematic diagram of the developing iris dilator muscle

at 6 months. During the sixth month, dilator muscle fibers (Dil. M) start to

differentiate from extensions of the anterior epithelial cells (AE) into thestroma (ST). These cells are located peripherally to the developing von

Michel's spur (MS), which itself is a pigmented projection of the anteriorepithelium, demarcating the posterior limit of the sphincter muscle (SP). In

the developing dilator muscle, myofilaments within the elongating

processes become arranged parallel to the stromal axis. Someundifferentiated anterior epithelial cells (UN) are present. In the sphincter,

which had originated earlier from the same layer of anterior epithelial cells,

connective tissue septa and a capillary (CA) start to grow between clumpsof cells, but connective tissue has not yet invaded between the muscle cells

and the anterior pigment epithelium beneath it. Eventually, the sphincter

muscle bundles become completely separated from the anterior epithelium,
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/017f.html


25/71

whereas the dilator muscle sheet remains as the multilayered stromalprojection of a part of this epithelium never separating from it. Therefore,

the dilator muscle is not a separate cellular layer, but rather a partial myoid

differentiation of cellular processes of the anterior neuroectodermalpigment epithelial cells. P, pupillary margin; PC, posterior chamber; PE,

posterior epithelium; PM, pupillary membrane.

Fig. 18. Excavation of the anterior chamber (AC) angle in

a fetus at 75 mm (3 months) is at a level with the rim ofthe optic cup, which is well ahead of the lens bow. The

corneal endothelium extends to the apex of the angle

(hollow arrow). The location of the future trabecularmeshwork is indicated by the arrow. On the side toward

the lens, the angle is limited by the forward extension of

the loosely woven mesenchyme over the optic cup

margin. Blood vessels in the recesses of the pigment epithelium (solidarrow) precede its infolding. LE, lens epithelium; pm, pupillary membrane.

Fig. 19. Angle at 7 months (approximately

225 mm). Apex of the wedge-shaped

trabecular meshwork (Tr) is not in theillustration. The corneal endothelium (En)

extends over one third of the trabecular

lamellae. The loose tissue in the angle

recess is isolated from the anterior chamber(AC) by processes of the reticular and

mesenchymal cells (hollow arrows). There are large clefts (*), some of

which are confluent, in the angle tissue. The angle recess extends beyond

the level of the middle of the trabecular meshwork, and the immatureSchlemm's canal (circled) is somewhat behind it. Ir, immature iris; Sc,

sclera. (Smelser GK, Ozanics V: The development of the trabecular

meshwork in primate eyes. Am J Ophthalmol 71:366, 1971.)

Fig. 20. The angle in a fetus late in the

ninth month (at approximately 37 weeks)

extends somewhat beyond the posterior

part of the trabecular meshwork, whichhas its apex at the termination of the

corneal endothelium (En). The scleral spur

(arrow) and the canal of Schlemm

(arrowhead) are in front of the angle.Loose tissue in the angle is indicated by the hollow arrow. AC, anterior

chamber; CM, ciliary muscle; cp, ciliary processes; C, cornea; Ir, iris; PC,

posterior chamber; Sc, sclera.

Anterior chamber angle formation seems to occur through a combination ofprocesses. Differential growth of the vascular tunic results in posterior
http://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/019f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/018f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/019f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/018f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/020f.htmlhttp://www.oculist.net/downaton502/prof/ebook/duanes/pages/v7/ch002/019f.htmlhttp://www.oculist

Documents

Prenatal Development of the Eye and Its Adnexa