Inhibition of advanced glycation end-products protects against retinal capillary basement membrane expansion during long-term diabetes.
The purpose of this study was to investigate the advanced glycation end-product (AGE)-inhibitory properties of aminoguanidine and to determine whether treatment in long-term diabetic rats can prevent basement membrane lesions of diabetic retinopathy. Four groups of male Wistar rats were studied: untreated diabetics injected with 45 mg/kg streptozotocin, aminoguanidine-treated diabetics, untreated controls, and aminoguanidine-treated controls. After 12 months' diabetes, the retinas from six animals were processed for electron microscopy or the retinal microvasculature was isolated using the trypsin digest technique. Stereological analysis was used to estimate quantitative ultrastructural changes in the retinal capillary-associated basement membrane. Serum AGEs were quantified by competitive AGE-ELISA, while microvascular-associated, immunoreactive AGEs were analysed on retinal trypsin digests. Aminoguanidine significantly reduced serum AGEs in the diabetic group (p < 0.001). In the retinal capillaries, there was a marked reduction in AGE immunoreactivity in the aminoguanidine-treated diabetics when compared with untreated diabetics. The surface area and absolute volume of the retinal capillary basement membrane were significantly increased in the diabetic rats when compared with non-diabetic controls (p < 0.001 and p < 0.001, respectively). Aminoguanidine treatment of diabetic rats protected against basement membrane expansion when compared with untreated diabetic counterparts. Aminoguanidine treatment prevents the development of diabetes-induced basement membrane expansion in retinal capillaries. The AGE inhibition properties of aminoguanidine suggest that AGEs play an important role in the complex pathogenesis of basement membrane thickening during diabetic retinopathy.
D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D002196:Capillaries / Q000473:pathology; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000517:prevention & control*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006146:Guanidines / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000378:metabolism / Q000473:pathology; D013997:Time Factors
D017127:Glycation End Products, Advanced; D006146:Guanidines; C004479:pimagedine