Pigment epithelium-derived factor (PEDF) prevents diabetes- or advanced glycation end products (AGE)-elicited retinal leukostasis

Microvasc Res. 2006 Jul-Sep;72(1-2):86-90. doi: 10.1016/j.mvr.2006.04.002. Epub 2006 Jun 22.

Abstract

Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. Leukocyte adhesion to retinal capillary endothelium (leukostasis) is a critical event in early diabetic retinopathy, whose process is mainly mediated by intercellular adhesion molecule-1 (ICAM-1). We investigated here whether PEDF could prevent diabetes- or advanced glycation end products (AGE)-elicited retinal leukostasis by suppressing ICAM-1 expression. Immunohistochemistry of 8-hydroxydeoxyguanosine (8-OHdG), an oxidative stress marker, showed intense staining in the nuclei of cells in the inner and outer plexiform layers of streptozotocin-induced diabetic rat retinas. Administration of PEDF or pyridoxal phosphate, an AGE inhibitor, decreased retinal levels of 8-OHdG and subsequently suppressed ICAM-1 gene expression and retinal leukostasis in diabetic rats. Further, intravenous administration of AGE to normal rats increased ICAM-1 gene expression and retinal leukostasis, which were blocked by PEDF. PEDF also inhibited the AGE-induced T cell adhesion to microvascular endothelial cells by suppressing ICAM-1 expression. These results demonstrated that PEDF inhibited diabetes- or AGE-elicited retinal leukostasis by suppressing ICAM-1. Our present study suggests that PEDF may play a protective role against early diabetic retinopathy by attenuating the deleterious effect of AGE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Cells, Cultured
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / pharmacology
  • Diabetes Complications*
  • Diabetes Mellitus / pathology*
  • Endothelial Cells / cytology*
  • Eye Proteins / physiology*
  • Glycation End Products, Advanced / pharmacology*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukostasis / metabolism
  • Leukostasis / prevention & control*
  • Microcirculation
  • Nerve Growth Factors / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Diseases / metabolism
  • Retinal Diseases / prevention & control*
  • Serpins / physiology*

Substances

  • Eye Proteins
  • Glycation End Products, Advanced
  • Nerve Growth Factors
  • Serpins
  • pigment epithelium-derived factor
  • Intercellular Adhesion Molecule-1
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine