Dose-dependent reduction of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by the aldose reductase inhibitor M79175

J Ocul Pharmacol Ther. 1997 Dec;13(6):517-28. doi: 10.1089/jop.1997.13.517.

Abstract

The onset and progression of retinal vascular changes associated with early diabetic retinopathy has been delayed in beagles fed 30% galactose diet for 38 months by treatment with the aldose reductase inhibitor M79175 (2-methyl-6-fluoro-spirochroman-4-5'- imidazolidine-2',4'-dione). Forty 9-month old male beagles were fed a daily diet containing either 30% non-nutrient filler or 30% galactose. One group of galactose-fed dogs was untreated while the others received M79175 at an average group dose of either 10 or 16 mg/kg/day. After 38 months one eye from 4 dogs from each group was enucleated and the isolated retinal vasculatures were objectively evaluated using an Olympus Cue-3 color image analysis system. Measurements of endothelium/pericyte (E/P) ratios, pericyte ghosts/1000 cells, pericytes and endothelial densities, and % acellularity per area and % acellularity per capillary length were conducted on a 0.1 mm square area surrounding the midpoints of 12 previously defined subregions. With the exception of endothelial densities which were not changed in galactose-fed dogs, M79175 treatment resulted in smaller changes in all parameters examined with the E/P ratio in dogs treated with 16 mg/kg/day M79175 not significantly different from that of age-matched non-galactose-fed dogs. These studies indicate that aldose reductase inhibitors provide dose-dependent protection against pericyte degeneration and subsequent microaneurysms formation.

Publication types

  • Comparative Study

MeSH terms

  • Aldehyde Reductase / antagonists & inhibitors*
  • Animals
  • Cataract / prevention & control
  • Diabetic Retinopathy / drug therapy*
  • Diabetic Retinopathy / physiopathology
  • Dogs
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage*
  • Galactose / administration & dosage
  • Imidazoles / administration & dosage*
  • Imidazolidines*
  • Male
  • Retinal Vessels / drug effects*
  • Retinal Vessels / pathology
  • Trypsin

Substances

  • Enzyme Inhibitors
  • Imidazoles
  • Imidazolidines
  • M 79175
  • Aldehyde Reductase
  • Trypsin
  • Galactose