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.
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Authors | H Neuenschwander, Y Takahashi, P F Kador |
Journal | Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics
(J Ocul Pharmacol Ther)
Vol. 13
Issue 6
Pg. 517-28
(Dec 1997)
ISSN: 1080-7683 [Print] United States |
PMID | 9436155
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Enzyme Inhibitors
- Imidazoles
- Imidazolidines
- M 79175
- Aldehyde Reductase
- Trypsin
- Galactose
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Topics |
- Aldehyde Reductase
(antagonists & inhibitors)
- Animals
- Cataract
(prevention & control)
- Diabetic Retinopathy
(drug therapy, physiopathology)
- Dogs
- Dose-Response Relationship, Drug
- Enzyme Inhibitors
(administration & dosage)
- Galactose
(administration & dosage)
- Imidazoles
(administration & dosage)
- Imidazolidines
- Male
- Retinal Vessels
(drug effects, pathology)
- Trypsin
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