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MJ Seiler, NS Cuenca, RB Aramant, H Kolb; Fetal Retinal Sheet Transplants to RCS Rat Retina: An Immunocytochemical Staining and Confocal Microscope Study . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3435.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To investigate the morphology of retinal neurons in fetal sheet transplants and in dystrophic RCS rat hosts. Methods: Sheets of E19-21 rat retina with its RPE were transplanted into 40-50d old RCS rats. Tissue sections were studied 5 to 12 months after surgery. Immunostaining was done using antibodies against protein kinase-C (PKC), calretinin (CR), calbindin (CB), parvalbumin (PV), recoverin (RC), microtubule-associated protein 1a (MAP1A), and cellular retinaldehyde binding protein (CRALBP). Results: Transplants developed more or less normal morphology, including photoreceptors with outer segments in contact with the cotransplanted RPE sheet. Mueller cells appeared well developed and usually formed an inner limiting membrane. At the transplant/host interface, areas were occasionally found where the inner limiting membrane was discontinuous. Staining with the calcium-binding proteins CR, CB, and PV and with RC and PKC was upregulated in the transplants. In the host retina, the same antibodies stained cells less intensely than in normals and cells looked misshapen and lost normal dendritic stratification. In areas where the transplants were separated from the host retina by a glial limiting membrane, transplant PKC rod bipolar cells and RC cone bipolar cells could not cross the transplant/host interface. In areas of inner limiting membrane disappearance, abnormal sprouting of horizontal, bipolar and amacrine cells could be observed in the transplants but it was unclear whether processes crossed the transplant/host interface. MAP1A-immunoreactivity (IR) in the transplants was much reduced indicating that the transplants contained few if any ganglion cells. However, MAP1A-IR processes occasionally crossed from transplant to host or visa versa. Conclusion: Neurons in fetal retinal transplants to RCS rats do not cross the transplant/host interface in any systematic manner. The transplant did not appear to affect degenerative changes in the dystrophic host retina. This indicates that strategies need to be developed to promote neural connectivity and to reverse the degeneration in the host retina. Supported by Foundation Fighting Blindness; Murray Foundation Inc.; Vitreoretinal Foundation, Louisville; Kentucky Lions Eye Foundation; Research to Prevent Blindness; and private funds.
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