PURPOSE: Earlier studies have revealed the association of advanced glycation end products (AGE) with the pathogenesis of various micro and macro vascular complications. The purpose of the present study is to localize AGEs, namely carboxy methyl lysine (CML-AGE) and methyl glyoxal-derived AGEs (MG-AGE), in retinal neovascular membranes and to quantify them in serum samples. METHODS: Surgically excised retinal neovascular membranes and serum samples obtained from patients with diabetic retinopathy, Eales' disease and nondiabetics were studied. Immunolocalization of AGEs namely CML-AGE and MG-derived AGEs was done using avidin biotin complex method and quantification was done by enzyme linked immunosorbent assay (ELISA). RESULTS: CML-AGE immunoreactivity was detected in all cases of Eales' disease and 61% cases of diabetic retinopathy and none in idiopathic epiretinal membrane (ERM). MG-AGE immunoreactivity was observed in approximately 15% of diabetic retinopathy and none in Eales' disease and and idiopathic ERM. Quantification of AGEs in serum samples revealed statistically significant increased levels of MG-AGE in diabetes, in relation to nondiabetics with idiopathic ERM and CML-AGE in Eales' disease, in relation to diabetics and nondiabetics with idiopathic ERM. CONCLUSION: Results from this study suggest that AGEs formed through glycation and glycoxidation may play an important role in the development of retinal neovascularization. The immunoreactivity of CML-AGEs in neovascular membrane and its increased levels in serum suggest that inspite of the normoglycemic status, glycoxidation and lipid peroxidation due to oxidative stress may trigger retinal neovascularization in Eales' disease, while MG-AGEs in diabetic membrane and serum suggest the role of glycation. Thus the mechanism of neovascularization in different pathological conditions could be different.
PURPOSE: Earlier studies have revealed the association of advanced glycation end products (AGE) with the pathogenesis of various micro and macro vascular complications. The purpose of the present study is to localize AGEs, namely carboxy methyl lysine (CML-AGE) and methyl glyoxal-derived AGEs (MG-AGE), in retinal neovascular membranes and to quantify them in serum samples. METHODS: Surgically excised retinal neovascular membranes and serum samples obtained from patients with diabetic retinopathy, Eales' disease and nondiabetics were studied. Immunolocalization of AGEs namely CML-AGE and MG-derived AGEs was done using avidin biotin complex method and quantification was done by enzyme linked immunosorbent assay (ELISA). RESULTS: CML-AGE immunoreactivity was detected in all cases of Eales' disease and 61% cases of diabetic retinopathy and none in idiopathic epiretinal membrane (ERM). MG-AGE immunoreactivity was observed in approximately 15% of diabetic retinopathy and none in Eales' disease and and idiopathic ERM. Quantification of AGEs in serum samples revealed statistically significant increased levels of MG-AGE in diabetes, in relation to nondiabetics with idiopathic ERM and CML-AGE in Eales' disease, in relation to diabetics and nondiabetics with idiopathic ERM. CONCLUSION: Results from this study suggest that AGEs formed through glycation and glycoxidation may play an important role in the development of retinal neovascularization. The immunoreactivity of CML-AGEs in neovascular membrane and its increased levels in serum suggest that inspite of the normoglycemic status, glycoxidation and lipid peroxidation due to oxidative stress may trigger retinal neovascularization in Eales' disease, while MG-AGEs in diabetic membrane and serum suggest the role of glycation. Thus the mechanism of neovascularization in different pathological conditions could be different.
Authors: J Zhang; H K Takahashi; K Liu; H Wake; R Liu; H Sadamori; H Matsuda; T Yagi; T Yoshino; S Mori; M Nishibori Journal: Br J Pharmacol Date: 2010-07 Impact factor: 8.739