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B.B. Thomas, R.B. Aramant, G.T. Qiu, S. Arai, Z. Chen, S.R. Sadda, M.J. Mahoney, M.J. Seiler; BDNF microsphere treatment increases functional effects of retinal transplants . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5184.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To test whether coating with brain derived neurotrophic factor (BDNF) microspheres could improve the functional effect of fetal retinal sheet transplantation in transgenic (rhodopsin mutant) S334ter–3 rats. Methods: S334ter–3 rats were exposed to blue light for 5 days to accelerate photoreceptor degeneration. At postnatal day (P) 29–43, the rats received in one eye subretinal transplants of retinal sheets from embryonic day 18–19 pigmented normal rats coated with BDNF microspheres. Beginning two weeks after surgery, visual acuity was monitored using an optokinetic head tracking apparatus. In addition, visual responses were recorded electrophysiologically from the superior colliculus (SC) at P78–98. Controls were rats without surgery or receiving BDNF microspheres only. Results: Rats that received BDNF coated transplants showed significant improvement in the optokinetic test (P<0.05, transplanted vs non–transplanted eye). With low light (1cd/m2) to preferentially stimulate rods, responses were recorded from the SC in a restricted area corresponding to the retinal location of the transplant. With stronger light (2500 cd/m2), responses were recorded from a larger SC area. The onset latency and the amplitude of the responses to low and strong light were close to that of the normal rats. Controls receiving only BDNF without transplants showed improvement in the optokinetic response in some of the rats; however, no responses from the SC with low light. No–surgery rats had no improvements in either test. Conclusions: BDNF treatment resulted in better optokinetic and visual electrophysiological responses to bright light (photopic), presumably due to rescue of host cones. In the transplant groups, both BDNF treated and non–treated rats showed visual responses to low light, possibly due to a direct effect of the transplant rods. Supported by: Foundation Fighting Blindness, Anonymous Sponsor, Foundation for Retinal Research, Fletcher Jones Foundation, NIH EY03040.
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