title: Early effects of high glucose in retinal tissue cultures Renin-Angiotensin system-dependent and -independent signaling.
abstract: 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(1) Receptor (AT(1)R); iii) activate src tyrosine kinase and increase phosphorylation of Pyk2, PLCgamma1 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 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 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.
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Gaddini
authors.forename: Marika
authors.initials: M
authors.lastname: Villa
authors.forename: Andrea
authors.initials: A
authors.lastname: Matteucci
authors.forename: Cinzia
authors.initials: C
authors.lastname: Mallozzi
authors.forename: Tamara C
authors.initials: TC
authors.lastname: Petrucci
authors.forename: Anna Maria M
authors.initials: AM
authors.lastname: Di Stasi
authors.forename: Lanfranco
authors.initials: L
authors.lastname: Leo
authors.forename: Fiorella
authors.initials: F
authors.lastname: Malchiodi-Albedi
authors.forename: Flavia
authors.initials: F
authors.lastname: Pricci
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015773:Enalaprilat / Q000494:pharmacology; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D051966:Phospholipase C gamma / Q000378:metabolism; D019000:Phosphotyrosine / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology*; D012160:Retina / Q000187:drug effects / Q000502:physiology*; D055351:Retinal Neurons / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D017362:Cyclic AMP Response Element-Binding Protein; D044140:Receptor, Angiotensin, Type 1; D019000:Phosphotyrosine; D051418:Focal Adhesion Kinase 2; D019061:src-Family Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D051966:Phospholipase C gamma; D015773:Enalaprilat; D005947:Glucose