Advanced Glycation End Products and Retinal Capillary Cell Death
Abstract Number: 889-P
Authors: RENU A. KOWLURU
Institutions: Detroit, MI
Results: Advanced glycation end-products (AGE) are considered as one of the important players in the development of retinopathy in diabetes. In the pathogenesis of retinopathy in diabetes, capillary cells undergo accelerated apoptosis. We have investigated the role of AGE in the accelerated retinal capillary cell death. Bovine retinal endothelial cells and pericytes were incubated in the presence of 0-5µM AGE-bovine serum albumin (AGE-BSA) for five days. The cell death was determined by performing ELISA for cytoplasmic histone-associated-DNA-fragments and by measuring the activity of the enzyme involved in the execution of apoptosis, caspase-3. Incubation of endothelial cells or pericytes with AGE-BSA increased oxidative stress by 70%, apoptosis by 40%, and activated caspase-3 by 35% compared to the cells incubated without AGE-BSA. The AGE-induced apoptosis and caspase-3 activation were similar to those obtained from the cells incubated in high glucose (20mM) conditions for five days. Since in diabetes retinal oxidative stress is increased and nuclear transcriptional factor is activated, we also investigated the effect of inhibition of oxidative stress on AGE-induced apoptosis and NF-kB activation. Co-addition of AGE-BSA and antioxidants (N-acetyl cysteine or lipoic acid) prevented oxidative stress, NF-kB activation and capillary cell apoptosis. These data strongly suggest that increased AGE in diabetes play an important role in retinal capillary apoptosis and oxidative stress is involved in this process. Inhibition of AGE in the retinal capillary cells could prevent their apoptosis, and ultimately, the development of retinopathy in diabetes.