Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats.
We have previously shown that long-term administration of aminoguanidine, an inhibitor of advanced glycosylation product formation, reduces the extent of experimental diabetic retinopathy in the rat by 85%. In order to determine whether the residual retinopathy that developed despite aminoguanidine was attributable to advanced glycation endproduct formation, a time-course study was performed in three different groups of male Wistar rats: non-diabetic controls (NC), streptozotocin-diabetic controls (DC) and streptozotocin-diabetic rats treated with aminoguanidine HCL, 50 mg/100 ml drinking water (D-AG). Eyes were obtained at 24, 32, 44 and 56 weeks of diabetes/treatment duration and morphologic evaluation was done on retinal digest preparations. At 56 weeks, retinal basement membrane thickness was additionally measured. After 24 weeks of diabetes, the number of acellular capillaries was significantly elevated in DC (44.6 +/- 5.7/mm2 of retinal area, NC 19.6 +/- 4.9; p < 0.001) and increased continuously over time (DC 56 weeks 87.4 +/- 15.1; p < 0.001 vs DC24 weeks). In contrast, acellular capillaries in D-AG increased over the first 24 weeks and then remained constant for the rest of the study (D-AG 24 weeks 35.7 +/- 5.18; p < 0.01 vs NC 24 weeks and NS vs DC 24 weeks; D-AG 56 weeks 42.0 +/- 6.20; p NS vs D-AG 24 weeks).(ABSTRACT TRUNCATED AT 250 WORDS)
Hammes
H P
HP
Third Medical Department, Justus-Liebig-University of Giessen, Germany.
Ali
S S
SS
Uhlmann
M
M
Weiss
A
A
Federlin
K
K
Geisen
K
K
Brownlee
M
M
D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D002196:Capillaries / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000503:physiopathology*; D006031:Glycosylation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D010972:Platelet Activating Factor / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D012171:Retinal Vessels / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D013997:Time Factors
D001786:Blood Glucose; D006146:Guanidines; D010972:Platelet Activating Factor; C004479:pimagedine