JAK-STAT is the major downstream signal pathway of cytokine families such as CNTF and is mainly regulated by STAT3. The present study examined the extent and the localization of unphosphorylated and phosphorylated (p-) STAT3 proteins in ischemia- reperfusion model of rat retina using by immunochemical methods, for clarifying involving mechanisms of STAT pathway in pathogenesis of ischemic neurodegeneration. Retina ischemia was induced by transiently increasing the intraocular pressure. In the normal retina, weak STAT3 immunoreactivity was visible in the proximal radial processes of Müller cells. However p-STAT3 immunoreactivity was not shown. Following ischemia-reperfusion, strong STAT3 immunoreactivity appeared in proximal processes and even in somata of Müller cell up to 3 days postlesion. p-STAT3 immunoreactivity appeared only in Müller cell somata up to 1 day postlesion. Quantitative evaluation by immunoblotting confirmed that STAT 3 and p-STAT3 expression levels continuously increased and showed a peak value at 1 day (to 300% of control levels) and 3 days (to 250% of control levels) postlesion, respectively and decreased again to 150% of controls at 4 weeks postlesion. Double immunocytochemistry with STAT3 and p-STAT3 or glutamine synthethase and CNTF antibodies revealed that most of all STAT3 and p-STAT3 labeled Müller cells underwent survival. These findings suggest that STAT3 produced and released by Müller cell may play an important role in the pathogenesis of ischemic injury in the rat retina.

Keywords: STAT3, phosphorylated STAT3, Mü,ller cell, ischemia-reperfusion, retina