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T.S. Vihtelic, S.M. Fimbel, D.R. Hyde; Regional Distribution of Photoreceptor Damage and Inner Nuclear Layer Cell Proliferation in Light-Treated Albino and Wild-Type Zebrafish . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5126.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Intense light causes photoreceptor damage in nonpigmented rodents and fish, while the retinas of pigmented rats are protected from light damage. Previously, we showed that 7 days (d) of constant light resulted in rod cell death and severe cone cell damage in albino zebrafish. Zebrafish rods and cones were regenerated from retinal progenitor cells residing in the inner nuclear layer (INL). The following studies further characterize the light-induced changes in the zebrafish retina. Specifically, we set out to i) determine if the photoreceptor layer damage and underlying INL cell proliferation exhibits a regional distribution, ii) compare the responses between albino and pigmented wild-type fish and iii) characterize the Müller glial cell response during light treatment. Methods: Adult albino and wild-type zebrafish were dark-treated for 14d and subjected to 7d of constant light. Light and transmission electron microscopy, as well as opsin and PCNA immunolabeling on serial sections were employed to assess and quantify photoreceptor layer damage and INL cell proliferation. For Müller cell evaluation, quantitative immunofluorescence, immunoblots and comparative RT-PCR assessed changes in glutamine synthetase (GS) and GFAP expression in light-treated albino retinas. Results: Severe damage to rod and cone photoreceptors occurred in the dorsal albino retinas, while damage in the pigmented dorsal retinas was mostly restricted to the rods. In contrast, outer nuclear layer cell body retention and intact rod outer segments characterized the ventral retinas of both the albino and wild-type fish. The regional distribution of proliferating cells correlated with the photoreceptor layer damage in both fish types. PCNA(+) INL cells in the dorsal retinas were increased 5-fold compared to the ventral retinas, although the average number of PCNA(+) cells per retinal region was up to 10-fold greater in the albino compared to the pigmented retinas. In the albino, Müller cell GS expression was down-regulated, while GFAP protein levels increased during the light treatment. Conclusions: Like the albino, wild-type zebrafish are susceptible to light-induced photoreceptor damage. The photoreceptor damage exhibits regional distribution, with the ventral photoreceptors relatively protected. The INL cell proliferation is graded and correlates with the level of damage in the overlying photoreceptor layer. The Müller cell response, including gene expression changes, is consistent with reactive gliosis.
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