VEGF164 is proinflammatory in the diabetic retina.

摘要: PURPOSE. The objectives of this study were to characterize the differential potency two major VEGF isoforms, 120 and 164 , for inducing leukocyte stasis (leukostasis) within retinal vasculature blood-retinal barrier (BRB) breakdown determine whether endogenous mediates leukostasis BRB in early established diabetes. METHODS. Retinal simultaneously quantified by combining concanavalin A lectin (ConA) perfusion labeling with a fluorophotometric dextran leakage assay. CD45 immunohistochemistry was performed confirm that ConA-stained cells leukocytes. compared nondiabetic rats receiving intravitreous injections or . intercellular adhesion molecule (ICAM)-1 protein levels studied Western blot ELISA, respectively. An anti-VEGF 164(165) aptamer (EYE001) administered injection 2-week 3-month diabetic rats, effect on quantified. RESULTS. Compared more potently increased ICAM-1 (2.2-fold), (1.9-fold), (2.1-fold, P 0.05). duration diabetes (P < 0.01) correlated closely 0.01, r = 0.889). isoform-specific blockade EYE001 resulted significant suppression both (72.4% 82.6%, respectively) (48.5% 55.0%, 0.01). CONCLUSIONS. On an equimolar basis, is at least twice as potent ICAM-1-mediated vivo. inhibition indicates important isoform pathogenesis retinopathy.