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A. Roca, P. Marjoram, J. Chen; Gene Expression Changes in Two Different Models of Light-induced Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):3557.
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Purpose: Arrestin knockout mouse is a good model to study light-induced degeneration due to constitutive signaling. We have previously shown that retinas from arrestin knockout mice undergo photoreceptor apoptosis after exposure to constant light within a frame time between 3 and 12 h (Roca et al, ARVO 2001). Our purpose is to compare the genes involved in the early stages of degeneration between the arrestin knockout and the BALB/C (albino) mouse models of light-induced retinal degeneration. Methods: Pigmented arrestin knockout, wild type control (C57Bl/6 x DBA/2) and albino (BALB/C) mice were raised in the dark and then exposed to fluorescent light (2000 lux) for 3 h. After exposure, retinas were immediately processed for total RNA isolation to screen genomic microarrays (murine U74Av2 chips, Affymetrix, Inc). Semi-quantitative real time RT-PCR of selected genes was used to validate changes in expression levels. Immunoblots were also performed to test the levels of certain phototransduction proteins. Results: About 12,000 probes were examined by cRNA array analysis. Light exposure led to a different profile in gene expression in arrestin knockout and BALB/C mice. We found that c-Fos is one of the differently expressed genes in BALB/C, whereas different clusters or EST were up-regulated in the arrestin knockout mice. No changes in expression in any of the phototransduction genes were observed after exposure to constant light for 3 h. To confirm these results Western blots were performed, which showed that transducin, recoverin, guanylate cyclase and RGS-9 did not change during the whole exposure to light. In contrast, a decrease in αßγPDE levels was observed after 12 h exposure to constant light. Conclusions: These results show that light-induced apoptosis in albino mice is mediated through genes involved in oxidative stress and is also c-fos dependent, while in the arrestin knockout mouse the light-induced apoptosis is c-fos independent. These results are consistent with previous studies by Hao et al (Nature Genetics, 2002). The different pattern expression can be used as a guideline to modify those gene levels in many eye diseases induced by light, such as Oguchi's disease.
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