title: Aminoguanidine treatment inhibits the development of experimental diabetic retinopathy.
abstract: Retinal capillary closure induced by hyperglycemia is the principal pathophysiologic abnormality underlying diabetic retinopathy, but the mechanisms by which this induction occurs are not clear. Treatment of diabetic rats for 26 weeks with aminoguanidine, an inhibitor of advanced glycosylation product formation, prevented a 2.6-fold accumulation of these products at branching sites of precapillary arterioles where abnormal periodic acid/Schiff reagent-positive deposits also occurred. Aminoguanidine treatment completely prevented abnormal endothelial cell proliferation and significantly diminished pericyte dropout. After 75 weeks, untreated diabetic animals developed an 18.6-fold increase in the number of acellular capillaries and formed capillary microaneurysms, characteristic pathologic features of background diabetic retinopathy. In contrast, aminoguanidine-treated diabetic animals had only a 3.6-fold increase in acellular capillaries and no microaneurysms. These findings indicate that advanced glycosylation product accumulation contributes to the development of diabetic retinopathy and suggest that aminoguanidine may have future therapeutic use in this disorder.
authors.affiliation: III. Medizinische Klinik, Justus-Liebig-Universität, Giessen, Federal Republic of Germany.
authors.forename: H P
authors.initials: HP
authors.lastname: Hammes
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: K
authors.initials: K
authors.lastname: Federlin
authors.forename: K
authors.initials: K
authors.lastname: Geisen
authors.forename: M
authors.initials: M
authors.lastname: Brownlee
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000517:prevention & control*; D005451:Fluorescein Angiography; D006031:Glycosylation; D006146:Guanidines / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology
chemical_list: D006146:Guanidines; C004479:pimagedine