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B. Jiang, S. D. Grozdanic, R. H. Kardon, M. H. Kuehn; Gene Expression in the Canine Glaucomatous Retina. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5901.
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© ARVO (1962-2015); The Authors (2016-present)
The pathophysiological events that lead to retinal ganglion cell (RGC) death in the glaucomatous retina remain unresolved. One approach to characterize these events is to determine the retinal gene expression profile during the progression of the disease. Dogs frequently develop glaucoma spontaneously and represent an attractive model for glaucoma research due to the large size of their eye, the chronic nature of their disease and the pathophysiological similarities to human glaucoma.
Eyes from five glaucomatous adult dogs with moderate to advanced glaucoma as well as from five control animals were obtained. Following RNA extraction the gene expression patterns were determined for each individual using Affymetrix gene chips (Canine Genome 2.0 array). Data were analyzed to identify those genes whose expression patterns significantly altered in the glaucomatous retina. Altered expression patterns of selected genes were confirmed by real-time PCR and immunohistochemistry.
Analyses of data obtained from canine retinae with and without glaucoma identified a large number of statistically highly significant gene expression changes. The most pronounced elevation of expression levels was observed for several components of the complement cascade, e.g. C3 (23-fold), C2 (14 fold) or C1q (11 fold), antigen presentation, e.g. HLA-DR (10 fold), as well as other mediators of inflammation, e.g. CSF1R (11-fold). Many of the gene products detected at lower levels appear to be associated with ganglion cells, e.g. GRIK1 (9-fold), NRN1 (5-fold), VSLN1 (11-fold), NEFH (8-fold) or ELAVL4 (7-fold).
These data are the first to describe changes in gene expression in the glaucomatous retina of a species with a large eye and spontaneously occurring chronic elevation of intraocular pressure. Most notably expression levels for mediators of inflammation were significantly elevated suggesting that inflammatory processes are a feature of the degenerating glaucomatous tissue. In contrast, transcripts for many RGC-related genes were detected at lower levels, presumably reflecting reduced numbers of RGC. Data derived from this study will aid in the design of neuroprotective treatment modalities that could subsequently be evaluated in this large eye model of glaucoma.
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