Early effects of high glucose in retinal tissue cultures Renin-Angiotensin system-dependent and -independent signaling

The early effects of the diabetic milieu on retinal tissue and their relation to the Renin-Angiotensin system (RAS) activation are poorly known. Here we investigated RAS signaling in retinas explanted from adult rats exposed for 48 h to high glucose (HG), with or without the Angiotensin Converting Enzyme inhibitor enalaprilat, which blocks RAS. HG was observed to i) initiate a phosphotyrosine-dependent signaling cascade; ii) up-regulate Angiotensin, Receptor (AT(1)R); iii) activate src tyrosine kinase and increase phosphorylation of Pyk2, PLC gamma 1 and ERK1/2; and iv) activate Akt and the transcription factor CREB. In the presence of enalaprilat, tyrosine phosphorylation signal and AT(1)R upregulation decreased and activation of PLC gamma 1 and CREB reverted, showing their relation to RAS signaling. In line with Akt activation, no apoptosis or synapse degeneration was found. Muller glia was activated, but in a RAS-independent manner. Our results suggest that, in early phases of HG exposure, a pro-survival cell program may be induced in the retina. (C) 2009 Elsevier Inc. All rights reserved.