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Y. Guo, P. Saloupis, D.W. Rickman; Neural Progenitor Cell Transplantation Following Light–Induced Photoreceptor Degeneration . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5383.
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Purpose: Transplantation of neural progenitor cells has been proposed as a potential restorative treatment for neurodegenerative diseases of the retina. However, major obstacles to therapeutic benefit from this approach are in achieving retinal phenotypic differentiation and functional integration of transplanted cells. Here, we sought to determine if photoreceptor differentiation of transplanted cells is enhanced by sustained delivery of brain–derived neurotrophic factor (BDNF) in a light damage model of photoreceptor degeneration. Methods: Photoreceptor damage was induced in Fisher 344 albino rats by constant exposure to light (700 lux) for 1 wk. Rats were then returned to cyclic light (12 hr ON/OFF) for 1 wk until unilateral subretinal transplantation of a) a suspension of adult hippocampal progenitor cells (AHPCs) expressing GFP (3 µ l of 5x103–5x104 cells; b) AHPCs + sustained–release, biodegradable microspheres containing BDNF (100 ng total concentration); c) AHPCs + BSA–containing microspheres (100 ng); or d) BDNF microspheres alone. Rats were sacrificed 2–9 wk later, and retinas were cryosectioned for analyses. Some sections were immunostained for retinal cell type–specific markers. Results: In normal, undamaged, control retinas, the outer nuclear layer (ONL) was 10–12 cells in thickness; 2 wk following light–induced damage, it was reduced to 3–5 cells; and at 8 wk, to 0–3 cells. Thinning of the ONL was accompanied by dramatic reductions in rhodopin and recoverin immunoreactivities. At 2 wk following transplantation, diffuse engraftment of AHPCs was observed. Most GFP–labeled cells were confined to the ONL. The number of engrafted cells did not appear to be influenced by the addition of BDNF– or BSA–microspheres. However, BDNF treatment resulted in enhanced preservation of host retinal morphology. By 8 wk post–transplant, numerous AHPCs in the ONL had adopted morphological characteristics of retinal neurons and had extended processes into the OPL. In addition, in retinas that received sustained–release BDNF microspheres, some transplanted AHPCs were seen to express rhodopsin or recoverin immuonreactivity. Conclusions: Transplanted AHPCs readily engraft into the light–damaged retina and preferentially target the ONL. Furthermore, sustained treatment with BDNF contributes to the preservation of the host retina and to the phenotypic differentiation of transplanted AHPCs.
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