Leukocyte-mediated endothelial cell injury and death in the diabetic retina

Endothelial cell death is a hallmark of diabetic retinopathy. Its occurrenc e is required for the formation of acellular (devitalized) capillaries, les ions that produce irreversible retinal ischemia through their inability to support blood now. The mechanisms underlying diabetic retinal endothelial c ell injury and death remain largely unknown. The current study demonstrates that adherent leukocytes are temporally and spatially associated with reti nal endothelial cell injury and death within 1 week of streptozotocin-induc ed experimental diabetes in rats. Moreover, the antibody-based neutralizati on of intercellular adhesion molecule-1 and CD18 is shown to prevent both l eukocyte adhesion and retinal endothelial cell injury and death. These data highlight the central and causal role of adherent leukocytes in the pathog enesis of diabetic retinopathy. They also underscore the potential utility of anti-intercellular adhesion molecule1- and anti-CD18-based therapies in the treatment of diabetic retinopathy, a newly recognized inflammatory dise ase.