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Robert Lin, Alexander De Guzman, Bibo Khatib, Bryce T McLelland, Anuradha Mathur, Leonard Kitzes, Biju B Thomas, Robert B Aramant, Magdalene J Seiler; Electrophysiological evidence for connectivity of fetal retinal sheet transplant in a novel immunodeficient retinal degenerate rat model. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):1823.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal degenerative (RD) diseases such as age related macular degeneration and retinitis pigmentosa cause a gradual loss of vision and have no effective treatment. Previously we have established a transplantation protocol for fetal retinal sheets in the S334ter line-3 RD rat model. The present study provides electrophysiological evidence that implanted fetal retinal sheets restore light response in a novel immunodeficient S334ter line-3 RD rat model (SD-Foxn1 Tg(S334ter)3Lav).
Control, non-RD rats were compared to immunodeficient S334ter line 3 RD rats (P30-P40) that were transplanted with intact fetal retinal sheets in the subretinal space. The size and location of the transplant was followed using OCT before electrophysiological testing. Prior to electrophysiological testing, rats were dark-adapted overnight. Transplanted rats were anesthetized, a craniotomy was performed, and the superficial layer of the superior colliculus (SC) was exposed. Single and multi-unit responses to a 40ms 6.5mcd/m2 light flash were recorded from locations in SC approximately 200μm apart. Responses were analyzed using a custom Matlab program.
OCT scans indicated that the placement of the retinal sheet transplants remained constant and were located in the subretinal space between the retinal pigment epithelium and the host retina. In control rats, visual responses were robust in all areas of the SC. However, in the immunodeficient S334ter rat the same stimulus was unable to elicit a response in most of the SC recording sites. Interestingly, robust responses were observed in a cluster of recording sites that were all within several hundred microns of each other.
Fetal retinal sheet transplants were stable for several months in immunodeficient S334ter rats and did not display any signs of host-graph rejection. The location of responses to light in the SC corresponded to transplant location in the retina. These data suggest that retinal sheet transplants are capable of integrating and surviving in the retina of immunodeficient rats. Additionally, the integration of the transplant into the retina of these animals is sufficient to restore light response in the SC.
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