Gaddini L, Villa M, Matteucci A, Mallozzi C, Petrucci TC, Di Stasi AM, Leo L, Malchiodi-Albedi F, Pricci F
Early effects of high glucose in retinal tissue cultures. Renin-Angiotensin System-dependent and-independent signaling. [JOURNAL ARTICLE]
Neurobiol Dis 2009 May 26.
The early effects of the diabetic milieu on retinal tissue and their relation to renin-angiotensin system (RAS) activation are poorly known. Here we investigated RAS signaling in retinas explanted from adult rats exposed for 48h 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(1) Receptor (AT(1)R); iii) activate src tyrosine kinase and increase phosphorylation of Pyk2, PLCgamma1 and ERK1/2; 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 PLCgamma1 and CREB reverted, showing their relation to RAS signaling. In line with Akt activation, no apoptosis or synapse degeneration was found. Müller glia was activated, but in RAS-independent manner. Our results suggest that, in early phases of HG exposure, a pro-survival cell programme may be induced in the retina.
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