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R. Lund, M.I. Pinilla, Y. Sauvé, S. Wang, B. Lu, N. Cuenca; Effect of human RPE cell line transplantation on synaptic relay in RCS rats. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5176.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the preventive effect of hRPE transplants on outer plexiform layer (OPL) synapses and to correlate the findings with retinal function. Methods:Six transplanted RCS rats were studied, together with unoperated and non–dystrophic controls. Transplanted rats received subretinal human RPE cell line, ARPE19, grafts at P22; all animals were maintained on oral cyclosporine immunosuppression. ERG was recorded at P56 and rats were sacrificed at P90 or P120. OPL was studied immunohystochemically using the following antibodies: bassoon and mGluR6, recoverin, rhodopsin, PKC, calbindin. Bassoon and mGluR6 relationship was studied in detail. Results:In normal rats, bassoon stains rod terminals as single punctate spots, which are paired with rod bipolar receptor sites stained with mGluR6: cone terminals are paired with mGluR6–positive postsynaptic disks on on–cone bipolar cells. During the course of degeneration, the rod and paired bipolar puncti are quickly lost: the cone synaptic patterns stained with bassoon/mGluR6 become disorganised. In areas of retina preserved by transplants, the normal organisation is preserved with evident rod terminal/ bipolar paring and clear clone synaptic sites. The level of connectivity was related to the degree of photoreceptor survival and the number of synapses decreased with increasing distance from the transplant area. Bipolar cells were well organized in the area of maximum rescue with relatively normal dendritic branching. ERG recordings showed at best both a–and b–waves being preserved, albeit of lower amplitude than normal. The magnitude of the ERG response was usually a good predictor of the level of anatomical preservation. Conclusions:ARPE19 transplants in RCS rats are able to maintain not only normal cell morphology, but also detailed substrates of connectivity in the OPL.
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