Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model.
Primary prevention with aminoguanidine-an inhibitor of advanced glycation end product (AGE) formation--has been successfully employed to prevent diabetic retinopathy in the rat. However, it is unknown whether inhibition of AGE formation is still effective in a secondary intervention strategy. The present study addresses this question by comparing secondary intervention with aminoguanidine with syngeneic islet transplantation in the rat model. After 6 months of diabetes, one group was treated with aminoguanidine (50 mg/100 ml drinking water; D-AG) while another group received syngeneic transplantation of collagenase-ficoll isolated islets by intraportal injection (Tx). After an additional 4 months, both groups were compared to a normal (NC 10) and diabetic (DC 10) control group. Retinal autofluorescence was increased 2.5-fold after 6 months and increased 3.7-fold after 10 months of diabetes (p < 0.001). Aminoguanidine and islet Tx retarded the further accumulation of autofluorescence equally (p < 0.001 vs DC 10), although the values were higher than those observed in DC at 6 months (p < 0.001). Diabetes was associated with a 2.7-fold increase in acellular capillaries after 6 months and a 4.1-fold increase after 10 months. Treatment with aminoguanidine or islet Tx reduced but did not completely attenuate the progression of vascular occlusion (p < 0.001 vs DC 10; D-AG vs DC 6, p < 0.05; Tx vs DC 6, p < 0.01). Both treatments reduced endothelial proliferation (22.4% after 10 months; p < 0.001) and completely arrested pericyte dropout (40% after 10 months; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Hammes
H P
HP
Third Medical Department, Justus-Liebig-University, Giessen, Germany.
Strödter
D
D
Weiss
A
A
Bretzel
R G
RG
Federlin
K
K
Brownlee
M
M
D000284:Administration, Oral; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000601:surgery; D003930:Diabetic Retinopathy / Q000503:physiopathology / Q000517:prevention & control*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D016381:Islets of Langerhans Transplantation; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D012171:Retinal Vessels / Q000187:drug effects / Q000473:pathology; D014185:Transplantation, Isogeneic
D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D006146:Guanidines; C004479:pimagedine