Abstract: Objective Both protein kinase C (PKC) and nitric oxide synthase (NOS) play a key role in the dysfunctions of early diabetic retina, but their interaction remains unclear. To investigate the effect of PKC on NOS expression and nitric oxide (NO) production in the retina of 2-week diabetic rats.Methods PKC inhibitor GF109203X was injected intravitreally after 2 weeks of streptozotocin-induced diabetes. PKC activity was measured by ELISA. NOS mRNA was analyzed by semi-quantitative RT-PCR. NO was determined indirectly as nitrite and nitrate.Results Increases of PKC activity, neuronal NOS (nNOS) mRNA expression and NO were found in the retina of diabetic rats compared with normal rats. Inducible NOS (iNOS) expression was slightly upregulated in diabetic retinas, but without any significant difference. Upregulation of nNOS mRNA was inhibited 12 h and 24 h after GF109203X was injected. NO also decreased 24 h after the injection compared with diabetic rats.Conclusion The results suggest that nNOS upregulation might be a result of PKC activation in the retina of early diabetes. This might be one of the mechanisms of retinal neuronal dysfunctions and vascular hyperpermeability. PKC inhibitor could reverse the abnormal increases of nNOS expression and NO.

Key words: diabetes, retina, protein kinase C, nitric oxide, nitric oxide synthase