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

Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10836-41. doi: 10.1073/pnas.96.19.10836.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridine Orange / metabolism
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Diabetic Retinopathy / chemically induced
  • Diabetic Retinopathy / metabolism*
  • Diabetic Retinopathy / pathology
  • Diabetic Retinopathy / prevention & control
  • Fluorescein Angiography
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Leukocytes / cytology
  • Leukocytes / metabolism
  • Leukostasis / pathology
  • Leukostasis / prevention & control*
  • Rats
  • Rats, Long-Evans
  • Retinal Vessels / metabolism*
  • Retinal Vessels / pathology
  • Time Factors

Substances

  • Antibodies, Monoclonal
  • Intercellular Adhesion Molecule-1
  • Acridine Orange