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Y.–W. Peng, G.–Q. Chang, Y. Hao, A. Gaitan, W. Zhang, F. Wong; Synaptic Integrity and Rod Photoreceptor Survival . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5346.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose:In several animal models of retinitis pigmentosa (RP), selective loss of invaginating rod bipolar cell dendrites in rod photoreceptor terminals gives rise to "vacant spaces" in the synaptic complexes (triads). Therefore, loss of synaptic integrity may be an early sign of rod degeneration caused by RP–inducing mutations. Many trophic factors, including brain–derived neurotrophic factor (BDNF), are known to confer protective effects on photoreceptors. We tested the hypothesis that, in a diseased retina, enhanced survival of rod photoreceptors may be correlated to the preservation of synaptic integrity. Methods:We performed TUNEL and EM analyses of retinal sections obtained from eyes of 3–week–old retinal degeneration slow (rds) mice that had intravitreal injection of BDNF (0.5 µg in 0.5 µl saline) at age 2 weeks. The fellow uninjected eyes served as controls. A vacant space was defined by (1) identifying a triad with one or two missing rod bipolar cell processes and (2) the presence within the triad a clearly defined vacant space that had no characteristic membranous lining. The density of vacant spaces (number per unit length) and the density of apoptotic (TUNEL–positive) nuclei were quantifiable parameters. Statistical analyses of the data were performed based on the two–tailed, one–sample t–test. Results:Consistent with previously published results, TUNEL–positive nuclei were abundant in the outer nuclear layer of 3–week–old rds retinas. Compared to normal retinas where virtually no vacant spaces were observed in the rod photoreceptor terminals, 12.6% of rod terminals counted in rds retinas were vacant spaces. Concurrently, compared to 84.6% in normal retinas, only 23.6% of rod terminals counted were triads in rds retinas. In comparison to untreated fellow eyes, injection of BDNF had the following effects: (1) the number of apoptotic photoreceptor nuclei was reduced by 33% (n=6, P=0.001) and (2) there was a 79% increase in density of triads (injected: 172.5/mm, uninjected: 96.5/mm; n=4, P=0.01) and a concurrent 76% decrease of vacant spaces (injected: 12.5/mm, uninjected: 51.5/mm; n=4, P<0.001) in the injected eye. Conclusions:The observed correlation between preservation of synaptic integrity and enhanced rod survival caused by intravitreal injection of BDNF suggested that the rod–to–rod bipolar cell synapse may be a critical site where cellular interactions could contribute to photoreceptor death. One of the mechanisms by which BDNF enhanced rod survival could be the preservation of synaptic integrity.
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