Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition

TLDR

Diabetic retinopathy, a leading cause of adult vision loss, primarily damages the retina through vascular leakage and nonperfusion. In streptozotocin‑induced diabetic rats, retinal leukostasis correlates with leakage and nonperfusion, and ICAM‑1 blockade reduces leukostasis by 48.5 % and leakage by 85.6 %, confirming leukocytes’ causal role and the therapeutic promise of ICAM‑1 inhibition.

Abstract

Diabetic retinopathy is a leading cause of adult vision loss and blindness. Much of the retinal damage that characterizes the disease results from retinal vascular leakage and nonperfusion. This study shows that diabetic retinal vascular leakage and nonperfusion are temporally and spatially associated with retinal leukocyte stasis (leukostasis) in the rat model of streptozotocin-induced diabetes. Retinal leukostasis increases within days of developing diabetes and correlates with the increased expression of retinal intercellular adhesion molecule-1 (ICAM-1). ICAM-1 blockade with a mAb prevents diabetic retinal leukostasis and vascular leakage by 48.5% and 85.6%, respectively. These data identify the causal role of leukocytes in the pathogenesis of diabetic retinopathy and establish the potential utility of ICAM-1 inhibition as a therapeutic strategy for the prevention of diabetic retinopathy.