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S. Wang, B. Lu, N. Bischoff, R. Lund; Morphological changes of retinal neurons in RCS rats during degeneration and after RPE cell line transplantation . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5172.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The dystrophic Royal College of Surgeons (RCS) rat shows a progressive loss of photoreceptors due to defect of retinal pigment epithelium (RPE) cells. The degeneration can be limited by transplantation of healthy RPE cells. Here we examined the effect of both degeneration and transplantation on the morphology of specific neurons of the inner retina. Methods: Dystrophic RCS rats (3 week old) received subretinal injection of human RPE cell line, ARPE19 (2x105/2µl/eye). Animals were killed at 1 week – 5 months post–transplantation. Retinal sections (10µm) were stained with cresyl violet, with cell specific markers (for retinal neurons) and with human–specific marker (for donor cells). Control animals were non–dystrophic and dystrophic RCS rats without transplants. All animals were immunosuppressed by adding cyclosporine to the drinking water. Results: In unoperated dystrophic RCS rats, there is loss of photoreceptors reducing to a single layer by 3 months. Changes are seen during this period in inner retinal structure, particularly in rod bipolars and in horizontal cells. Transplanted ARPE19 cells survive for at least 5months post–transplantation, forming lumps at 1 week and spreading out by 2 weeks as a sheet over the host RPE layer, comprising 1 or 2 layers of cells. Distant to the graft, the retina appears similar to an unoperated control. However in the region of the graft, improved structural organization was seen even 1 week post–transplantation. At 5 months there is good photoreceptor rescue of up to 5 nuclei deep: inner and outer segments are well organized as indicated by rhodopsin and recoverin staining. The morphology of inner retinal neurons, such as bipolars and horizontal cells is indistinguishable from nondystrophic controls while in the retina distant from graft, the pathological appearance seen in dystrophic controls including sprouted bipolar and horizontal cell dendrites is evident as is disorder of the inner nuclear layer. Conclusions: RPE transplant can preserve not only the photoreceptor morphology, but also inner retinal structure in RCS rats.
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