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S. S. Hunter, D. L. Stenkamp; The Photoreceptor Damage Response: A Comparative Genomics Approach. Invest. Ophthalmol. Vis. Sci. 2009;50(13):1282.
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© ARVO (1962-2015); The Authors (2016-present)
Many retinal disorders involve death of photoreceptor cells. The adult mammalian retina is incapable of replacing these cells, limiting options for treatment. In contrast, the teleost fish is capable of regenerating a functional retina after photoreceptor damage. We have carried out a meta-analysis of several microarray datasets in order to identify genetic components involved in these differential responses.
Analyses were carried out in R, using packages from Bioconductor. Retinal tissue datasets included two from zebrafish and one from mouse following light damage, as well as one from rat following a retinal tear. Datasets from regenerating zebrafish heart and fin were also analyzed. Differentially expressed genes were identified using Significance Analysis of Microarrays. Homology was defined using the BioMart database, and hierarchical clustering was used to identify sets of co-expressed genes. These analyses guided the selection of candidate genes for ongoing characterization of gene expression following acute and chronic retinal damage.
The zebrafish and mouse datasets had 94 differentially expressed homologs in common. With few exceptions these genes showed conserved temporal expression patterns. Most of these "photoreceptor damage response" genes have roles in stress response/apoptosis, protein synthesis, transcription and signal transduction, and in cell cycle regulation and DNA synthesis. 14 genes including cell signaling factors SOCS3 and granulin, have known functions in regenerative responses to tissue damage. 1,543 genes were differentially expressed in zebrafish but not mouse, while fewer genes (128) were differentially expressed following damage in mouse but not zebrafish. The latter "mouse-specific" set includes components of the endothelin signaling system. Preliminary RT-PCR results corroborate that the zebrafish retina does not engage in robust endothelin signaling immediately after damage. 38 differentially expressed genes were common to all zebrafish tissue damage datasets, the majority of these genes showed similar temporal expression patterns.
A surprisingly small set of genes plays a conserved role in responding to photoreceptor damage in different animal models, and an even smaller set participates in a response that is conserved across tissues. Comparisons with microarray datasets derived from embryonic retina are underway.
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