30.P1 Functional Properties of Subretinal Transplants in Rabbitdownloads.hindawi.com/journals/np/1992/725734.pdf · 2019-08-01 · uppertrace, andoccursbetween2.5and3.0s of the 5.0s

30.P1

Functional Properties of Subretinal Transplants in RabbitA.R. Adolph, C.L. Zucker, B. Ehinger2 and A. Bergstr6m2

Schepens Eye Research Institute and Harvard Medical School, Boston 02114, MA, USA;2Department of Ophthalmology, University ofLund, Sweden

281

There has been a rapid growth in researchfocused on retinal transplantation as a strategyfor restoration of or rescue of function in retinasrendered afunctional by disease or trauma. Thisstrategy has been partially stimulated by recenttransplantation efforts in brain related toneurodegenerative diseases such as Parkinson’s,Huntington’s, and Alzheimer’s. These latterefforts have been hindered by a dearth of infor-mation regarding the specific properties of theinputs, intrinsic processing and outputs withinthe brain underlying these diseases. This is espe-cially significant when attempting to study cor-related functional and structural properties ofthe implanted tissue. In contrast to such studies,this research utilizes the retina, of which there isgreater knowledge about the inputs (complexlight patterns), intra-retinal processing andanatomical micro-circuitry, and the output(patterns of ganglion cell activity). Our researchdemonstrates, for the first time, organized, com-plex physiological function and its underlyingneuronal microcircuitry in mammalian sub-retinal transplants.

Figure 1. Electrical activity inisolated grafts in response to light. Shutteropen is indicated by the dark bar in theupper trace, and occurs between 2.5 and 3.0sof the 5.0s peristimulus time frame. Upperdata panel is a peristimulus spike histogramto 27 repetitions of the stimulus cycle. Theabscissa in all traces is time in seconds. Thehistogram ordinate is in hundreds ofspikes/sec, i.e. peak response is 159.2/sec.Lower data panel is averaged LERGresponse. A 20gV calibration pulse occursbetween 0.25 and 0.Ssec of each response,which is averaged along with the LERGsignal. The spike response is transient ON-OFF and the LERG has a distincthyperpolarizing transient at light ON (ca.40gV) and an aaemuated one at OFF (less

A

Grafts which develop from transplantingfragments of embryonic donor retina into thesubretinal space of a mature host exhibit atypicalretinal organization. A combination of light andelectron microscopy plus intracellular dyemarking has shown that the grafts often developregions containing "rosettes" of photoreceptorssurrounded by appropriately layered retinalelements. The transplants contain abundantlythe specific cellular and synaptic componentswhich are necessary for phototransduction andfor the processing of visual information in afashion similar to that carried out by normalretinas.

In testing the effect of this organization ongraft functional properties, we isolated the graftto avoid contamination of graft responses byhost retinal activity. Light-driven responses wererecorded by microelectrodes from this prepara-tion maintained in vitro. Local electroretino-grams and spike-like responses to flashed spotstimuli is transient ON or ON-OFF. The ampli-tudes and durations of these response compo-nents depend on stimulus diameter, sometimes

Stimulus Timimg

Sum of 27 cycles1.592

.5

0

B

0 .5 1.5 2 2.5 3 3.5 4 4.5 5

Fig. 1

(C) FREUND PUBLISHING HOUSE LTD., LONDON. JOURNAL OF NEURALTRANSPLANTATION & PLASTICITY, Vol. 3, No. 4, 1992

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in a way suggesting center-surround receptivefield organization and spatial tuning. Responseamplitudes are also a function of light intensity.The local electroretinogram transient hyper-polarizations at light-ON and -OFF may reflectlight-induced amacrine cell activity (M-waves).Thus, these rabbit retinal grafts contain theneural components, local synaptic circuitry andexhibit the electrophysiological responses neces-sary to process complex visual information.

CONCLUSIONS

Based on intracellular filling, light and elec-tron microscopy, retinal grafts contain the major

neuronal cell types present in normal retinas,with the possible exception of ganglion cells.These neuronal elements are organized at thecellular and synaptic levels in a fashion appro-priate for retinal function. Retinal grafts showlight responsiveness representing photoreceptorfunction and localized visual information pro-cessing. The spatial properties of the responsesindicate possible center-surround functionalorganization in the outer plexiform layer. Thetemporal properties, such as ON-OFF light re-sponses, suggest inner plexiform layer signalprocessing. Taken together, these resultsdemonstrate a degree of functional ability andcapacity in retinal transplants required for usefultherapeutic purposes.

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30.P1 Functional Properties of Subretinal Transplants in Rabbitdownloads.hindawi.com/journals/np/1992/725734.pdf · 2019-08-01 · uppertrace, andoccursbetween2.5and3.0s of the 5.0s