Poly (ADP-Ribose) Polymerase Inhibitor (PJ34) Inhibits Leukocyte Entrapment in the Retinal Microcirculation of Diabetic Rats

Abstract

Abstract: : Purpose: Endothelial cell damage in the diabetic retina is a primary event in the pathogenesis of diabetic retinopathy and is associated with the presence of leukocytes. Several studies reported that leukocyte entrapment increases in the retina with early stage diabetes. Recent studies indicate that activation of poly(ADP-ribose) polymerase (PARP) contributes importantly to development of endothelial dysfunction in diabetes. We evaluated quantitatively the effectiveness of PARP inhibitor, PJ34, in the treatment of leukocyte entrapment in the retinal microcirculation of diabetic rats. Methods: Diabetes was induced in male Wister rats by intraperitoneal injection of 60 mg/kg of streptozotocin. Rats were divided into three groups: group A, controls; group B, untreated diabetes; and group C, diabetes treated with PJ34 (10 mg/kg oral lavage twice daily). All experiments were performed 4 weeks after initiation of treatment. Leukocyte entrapment in the retinal microcirculation was quantitatively evaluated in vivo with acridine orange digital fluorography. Results: The number of leukocytes trapped in the retinal microcirculation 30 minutes after dye injection was significantly greater in group B (32.1±4.7 cells/mm²) than in group A (11.3±4.5 cells/mm²) (p<0.05). Compared with group B, the number of trapped leukocytes significantly decreased in group C (24.1±4.2 cells/mm²) (p<0.05). Conclusions: Treatment with PJ34 decreased enhanced leukocyte entrapment in the retinal microcirculation during the early diabetic period. PJ34 may reduce retinal microvascular disturbance in early diabetes.

Keywords: diabetic retinopathy • diabetes • imaging methods (CT, FA, ICG, MRI, OCT, RTA, S