Effects of aldose reductase inhibitors and galactose withdrawal on fluorescein angiographic lesions in galactose-fed dogs.
OBJECTIVE
To assess the effect of aldose reductase inhibitor (ARI) M79175 (2-methyl-6-fluoro-spiro-chroman-4-5'-imidazolidine-2',4'-dione) administration and galactose withdrawal on the progression of retinal changes using fluorescein angiography in galactose-fed dogs.


METHODS
Thirty male beagles were randomized into 4 groups. Three dogs were fed a normal control diet containing 30% nonnutritive fiber for 74 months (control group), 11 dogs a 30% galactose diet for 74 months (continuous galactose group), 8 dogs a 30% galactose diet for 36 months followed by replacement with a normal diet for 36 months (galactose withdrawal group), and 8 dogs a 30% galactose diet supplemented with M79175 for 34 months followed by replacement with a normal diet and removal of M79175 treatment for 38 months (ARI-treated galactose withdrawal group). Stereoscopic color fundus photography and fluorescein angiography, performed at baseline and follow-up, were assessed for the clinical development of retinopathy, including the first appearance of hyperfluorescence, varying severity of retinal nonperfusion, and retinal neovascularization. Histopathologic features were examined in selected dogs.


RESULTS
All dogs in the 3 groups fed the 30% galactose diet developed areas of hyperfluorescence and nonperfusion. Of these dogs, only those supplemented with the ARI did not develop areas of nonperfusion greater than or equal to half the field and retinal neovascularization. Parametric survival analysis showed significant differences (galactose withdrawal group vs ARI-treated galactose withdrawal group) in the median times to the development of nonperfusion greater than or equal to half the field (P =.003) and retinal neovascularization (P =.03).


CONCLUSIONS
Normalization of glycemic control with galactose withdrawal and ARI treatment may delay the onset and progression of retinal lesions in galactose-fed dogs. Clinical Relevance Perfect glycemic control after a period of poor control does not completely prevent the progression of retinal lesions. Therapy with ARIs may potentially be important in the prevention of retinal lesions associated with diabetic eye disease.
Cusick
Michael
M
National Eye Institute, National Institutes of Health, and Howard Hughes Medical Institute - National Institutes of Health Research Scholars Program, Bethesda, MD 20892, USA.
Chew
Emily Y
EY
Ferris
Frederick
F
Cox
Terry A
TA
Chan
Chi-Chao
CC
Kador
Peter F
PF
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003930:Diabetic Retinopathy / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control*; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005451:Fluorescein Angiography; D005690:Galactose / Q000008:administration & dosage*; D007093:Imidazoles / Q000627:therapeutic use*; D048289:Imidazolidines; D008297:Male; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000175:diagnosis / Q000517:prevention & control; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; C037070:M 79175; D000449:Aldehyde Reductase; D005690:Galactose