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D. Wang, K. Rodgers, Y. Ben, A. Ray, C. L. Grosskreutz; Transcriptional Up-Regulation of Stat3 and Stat5a in Experimental Glaucoma. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2116.
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Recent studies suggest that multiple intracellular pathways are involved in RGC death in glaucoma. The importance of Jak-Stat pathway signaling in neuronal survival is well established. This aim of the present study was to examine the transcriptional Jak/Stat pathway in a rat glaucoma model.
The IOP of one eye was elevated by hypertonic saline episcleral vein injection in Brown Norway rats. In one group of rats (n = 5), RGCs were Fluorogold-labeled 7 days prior to glaucoma-inducing surgery. When the elevated IOP had been sustained for 10 days, the rats were sacrificed and their retinas were removed and processed for tissue sectioning. An equal number of RGCs were isolated by laser capture microdissection (LCM) from retinal tissue sections of rat eyes with and without high IOP. RT-qPCR was used to determine the Stat3 and Stat5 message level of captured RGC. Immunohistochemistry was performed for Stat3 and Stat5a protein localization. In the second group (n = 8), rats were sacrificed for retinal RNA extraction when the elevated IOP had been sustained for 10 days. qRT-PCR was performed to examine the expression of Stat3 and Stat5a in the whole retina.
Compared to the normal RGC, the message levels of Stat3 and Stat5a were 7.28-fold and 2.74-fold upregulated in the glaucomatous RGC. Increased mRNA expression of Stat3 (3.79±1.96, P = 0.004) and Stat5a (2.70 ±1.87, P = 0.036) were found in the whole retina following IOP elevation. Under conditions of high IOP, increased Stat3 immunoreactivity is seen in the ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL) as well as in cell processes. Increased stat5a staining also is seen in the GCL, IPL and INL. Moreover, Stat3 and Stat5a are colocalized in Fluorogold labelled RGC. Increased Stat3 and Stat5a levels were detected in RGC in experimental glaucoma.
Our results revealed that both message and protein levels of Stat3 and Stat5a were increased in retina and specially in RGC in response to elevated IOP. The changes in Stat3 and Stat5a may be important prosurvival mediators following IOP elevation. We speculate that JAK/STAT signaling could be an important endogenous neuroprotective or compensatory response in glaucoma.
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