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R. Naskar, N. Schmitz, W. Paulus, S. Thanos; Retinal Gene Expression in Hereditary and Experimentally Induced Rat Models of Glaucoma . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3770.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To examine the gene expression profiles in rat retinas with either experimentally induced or hereditary glaucoma Methods: The intraocular pressure (IOP) was elevated in adult Sprague–Dawley rats by cauterizing two episcleral veins, and elevated IOP developed spontaneously in the hereditary rat model. Total RNA was isolated from independent samples and reverse transcribed into cDNA. Labeled cDNAs from control and glaucoma retinas were cohybridized on Rat 10k microarrays (MWG) to determine changes in gene expression. The regulation of selected genes in both glaucoma models was confirmed using quantitative Real–time PCR. The localization of the corresponding gene products was determined using immunohistochemistry. Results: The IOP was elevated to 25 ± 2.0 mmHg and 37 ± 5.0 mmHg in the induced and hereditary glaucoma eyes, respectively. Elevated IOP shifted the retina’s program of gene expression in both glaucoma models, with 541 (induced glaucoma) and 861 genes (hereditary glaucoma) showing a change in expression. These genes included those involved in the cell cycle, apoptosis, maintenance of the extracellular matrix, phototransduction, signaling, and transcription. The changes in gene expression of ceruloplasmin, galectin–3, c–myc, and tissue inhibitor of matrix metalloproteinase–1 were validated and confirmed using real–time PCR. The protein product of c–myc was found to be localized to astrocytes and Müller cells in the retina of the hereditary–glaucoma retinas. Conclusions: The effects of the severity and duration of IOP on the expression pattern of some genes differs between the glaucoma models. Cell–cycle, apoptosis, and transcription genes seem to be regulated in the glaucomatous retina and could provide clues about the signaling cascades involved in glaucomatous damage.
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