Ciliary neurotrophic factor (CNTF) is a neurocytokine that regulates numerous aspects of homeostasis and immune response in the nervous system through activation of the JAK-STAT signal transduction pathway. We investigated the expression patterns of both CNTF and its signal transduction protein STAT3 in the rat retina following diabetic injury using immunohistochemistry and western blot analysis. Experimental insulin-dependent diabetes was produced by a single intravenous injection of streptozotocin and the rats were studied 1, 4, 12 and 24 weeks later. Both CNTF and STAT3 were expressed in the normal retina, but were restricted to the end feet of Müller cells. In one and four week diabetic rat retinas, somata and proximal radial processes of Müller cells also expressed CNTF and STAT3. Both proteins were intensely expressed in the proximal processes and even in the distal radial processes of Müller cells at 12 and 24 weeks. Phosphorylated STAT3 was expressed in Müller cell nuclei by four weeks, and for up to 24 weeks of diabetes. The altered expression patterns were in accordance with quantitative results throughout the experiments. Thus, CNTF in the retina is generated in and partly transduced back to the Müller cells. The STAT3 signal transduction pathway appears to play a central role in glial reaction and cell survival in response to diabetic injury.

Keywords: neurocytokine, insulin-dependent diabetes, autocrine mode, immunochemical techniques