Lens epithelial cell apoptosis initiates diabetic cataractogenesis in the Zucker diabetic fatty rat

Graefes Arch Clin Exp Ophthalmol. 2010 Jun;248(6):811-8. doi: 10.1007/s00417-010-1313-1. Epub 2010 Feb 17.

Abstract

Background: It has been suggested that damage of lens epithelial cell (LEC) may play an important role in cataract formation. Nitric oxide is involved in cataract development. Here, we investigated the relationship between LEC damage and iNOS expression in the Zucker diabetic fatty (ZDF) rat.

Methods: At 21 weeks of age, the eyes were enucleated and the lens opacity was then examined. Apoptosis were detected by TUNEL assay, and the expression of iNOS and NF-kappaB activation were studied by immunohistochemistry and southwestern histochemistry respectively.

Results: In 21-week-old male ZDF rats, cataract was developed, TUNEL-positive LECs were markedly increased, and the expression levels of iNOS mRNA and protein were significantly upregulated. The expression pattern of iNOS was closely correlated with apoptotic change of LECs. In addition, advanced glycation end products (AGEs) were accumulated in cytoplasm of LECs. Activated NF-kappaB was mainly detected in nucleus of LECs.

Conclusions: The higher expressions of AGEs, NF-kappaB and iNOS in LECs of diabetic rats suggest that these factors are involved in apoptosis of LEC alterations related to diabetic cataract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Blotting, Western
  • Cataract / etiology*
  • Cataract / metabolism
  • Diabetes Complications*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • Glycation End Products, Advanced / metabolism
  • Histocytochemistry
  • In Situ Hybridization
  • In Situ Nick-End Labeling
  • Lens, Crystalline / metabolism
  • Lens, Crystalline / pathology*
  • Male
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Zucker
  • Up-Regulation

Substances

  • Glycation End Products, Advanced
  • NF-kappa B
  • RNA, Messenger
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat