Aminoguanidine does not inhibit the initial phase of experimental diabetic retinopathy in rats

Abstract

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)

Apoptotic death of photoreceptors in the streptozotocin-induced diabetic rat retina

“…Progression of diabetic retinopathy is considerably prevented by aminoguanidine [42]. It is also clarified that the initial phase of diabetic retinopathy is through non aminoguanidine-inhibited mechanism [42].…”

“…Progression of diabetic retinopathy is considerably prevented by aminoguanidine [42]. It is also clarified that the initial phase of diabetic retinopathy is through non aminoguanidine-inhibited mechanism [42]. In con-trast, aminoguanidine has been suggested to act on restoring the number of nNOS-containing neurons in the short-term and long-term diabetic retinas, as mediated by the inhibition of AGE formation [43].…”

Pharmacological Inhibition of Diabetic Retinopathy

“…Another drug, aminoguanidine, was shown to inhibit many sequelae of advanced glycation end product (AGE) formation (11)(12)(13) and was observed to have beneficial effects on a number of diabetes-induced alterations of tissue function and structure (14 -20). Moreover, aminoguanidine was found by Hammes et al (21,22) and later also by Kern and Kowluru (23) to inhibit the development of some retinal lesions in diabetic rats. In our experience, diabetic rats develop the early stages of diabetic retinopathy, but do not reproducibly develop microaneurysms and advanced lesions of the retinopathy (7).…”

The relationship of glycaemic level to advanced glycation end-product (AGE) accumulation and retinal pathology in the spontaneous diabetic hamster

“…Since endothelial cells do not leave behind such traces when they disappear, their fate during the initial course of retinal damage is uncertain, despite indication for both focal loss, leading to acellular capillaries, and focal proliferations leading to hypercellular vessels and microaneurysms [4,5]. Pericyte loss and acellular, occluded capillaries have been found in diabetic animals, in which the natural course of diabetic retinopathy has been studied [6,7]. Diabetologia (1998) Summary To assess the relationship between glucose and advanced glycation end products (AGE) and the relationship between AGE and retinal changes in vivo, we studied the time course of retinopathy over 12 months in trypsin digest preparations and measured glycaemia and retinal AGE in spontaneous diabetic hamsters of mild (MD) and severe (SD) phenotypes.…”