Triamcinolone suppresses retinal interruption of proinflammatory vascular pathology via a potent signal-regulated activation of VEGF during a relative hypoxia

We examined the effect of triamcinolone acetonide (TA), a corticosteroid, on the relationship between vascular pathophysiology and vascular endothelial growth factor (VEGF) activation in the retina of a rat model of oxygen-induced retinopathy (0111). 0111 was induced by exposure of hyperoxia (80% oxygen) to Sprague-Dawley (SD) rats from P2 to P14 and then returned to normoxic conditions. TA was intravitreal-injected once into the right eye of OIR rats at P15. Effects of TA on vascular pathophysiology or changes of various genes in response to hypoxia and/or proinflammation under hypoxic retina were assessed by the Evans-blue method, fluorescein isothiocyanatedextran (FITC-D) infusion, immunoblotting, and ELIZA. TA not only reduced retinal neovascularization and vascular leakage in the OIR-rat retina, but also blocked the induction of hypoxia-response proinflammatory genes before it negatively controlled VEGF activation. These findings suggest a potential that TA suppresses retinal neovascular pathophysiology via proinflammation-mediated activation of VEGF during hypoxia. (c) 2007 Elsevier Inc. All rights reserved.