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A. C. Morris, T. Scholz, S. E. Brockerhoff, J. M. Fadool; Identification of Genes Associated With the Regenerative Response to Rod Photoreceptor Degeneration in Zebrafish. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3004.
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In contrast to humans and other adult mammals, the retinas of fish and amphibians exhibit persistent neurogenesis and the capacity for injury-induced regeneration. Using two genetic models of photoreceptor degeneration in zebrafish, we have shown that distinct regenerative responses are observed following selective loss of rod or cone photoreceptors. Whereas the rod response is mediated exclusively by mitotic rod progenitor cells, the cone response is mediated by a subset of Muller glia. To identify genes that are important for the selective regeneration of rods or cones, we have compared the gene expression profile of wild type retinas with those from XOPS-mCFP transgenic animals that experience rod degeneration.
Retinal RNA was prepared from four individual wild type and XOPS-mCFP adults. Labeled cRNA was hybridized to an Agilent zebrafish microarray containing probes for roughly 21,500 zebrafish genes. Each of the four separate hybridizations included a dye-swap control. A subset of genes whose expression showed significant changes between wild type and XOPS-mCFP retinas were further analyzed by standard RT-PCR and real-time quantitative RT-PCR. Gene expression was also analyzed in the pde6c mutant, a zebrafish model of cone degeneration.
Significant changes (p<0.005 and correction for false discovery rate) were detected in the expression of 1135 transcripts. RT-PCR for a subset of these genes verified the expression changes identified in the microarray analysis. As expected, expression of genes involved in rod phototransduction was significantly reduced in the XOPS-mCFP retinas compared to wild type. Genes displaying elevated expression in XOPS-mCFP retinas relative to wild type are involved in several biological processes, including DNA replication, retinal development, stem/progenitor cell maintenance, and chromatin modification. Interestingly, genes such as Stat3 and ash1a, which are upregulated in response to acute retinal damage, do not show a change in expression in response to rod degeneration.
Our study has identified genes that may be involved in the retinal response to rod degeneration. This gene set, along with our two genetic models of rod and cone degeneration, should provide new avenues for investigating the molecular determinants of selective photoreceptor cell regeneration.
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