title: Dose-dependent reduction of retinal vessel changes associated with diabetic retinopathy in galactose-fed dogs by the aldose reductase inhibitor M79175.
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.
authors.affiliation: Laboratory of Ocular Therapeutics, National Eye Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: H
authors.initials: H
authors.lastname: Neuenschwander
authors.forename: Y
authors.initials: Y
authors.lastname: Takahashi
authors.forename: P F
authors.initials: PF
authors.lastname: Kador
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D002386:Cataract / Q000517:prevention & control; D003930:Diabetic Retinopathy / Q000188:drug therapy* / Q000503:physiopathology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D005690:Galactose / Q000008:administration & dosage; D007093:Imidazoles / Q000008:administration & dosage*; D048289:Imidazolidines; D008297:Male; D012171:Retinal Vessels / Q000187:drug effects* / Q000473:pathology; D014357:Trypsin
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; C037070:M 79175; D000449:Aldehyde Reductase; D014357:Trypsin; D005690:Galactose