Protective Effects of Glucosamine on Oxidative-Stress and Ischemia/Reperfusion-Induced Retinal Injury

PURPOSE. To investigate the protective effects of glucosamine (GlcN) using oxidative stress and rat models of ischemia-reperfusion (I/R) injury and to determine the antiapoptotic and anti-inflammatory mechanisms of GlcN treatment. METHODS. We determined the effects of GlcN and the levels of O-linked N-acetylglucosamine (O-GlcNAc) in in vitro retinal ganglion cells (RGCs) treated with or without H2O2. The survival and apoptosis rates of RGCs were compared after the addition of GlcN, glucose, or O-(2-acetamido-2-deoxy-Dglucopyranosylidene) amino-N-phenylcarbamate (PUGNAc). Retinal I/R injury was induced in Sprague-Dawley rats by elevating the IOP to 110 mm Hg for 60 minutes. An intraperitoneal injection of GlcN (1000 mg/kg) or normal saline was administered in the different groups, including a control group, a GlcN group, an I/R group, a GlcN+I/R group (1000 mg/kg GlcN 24 hours before I/R injury), and an I/R+GlcN group (7-day period of 1000 mg/kg GlcN 24 hours after I/R injury). The rats were killed 7 days after the I/R injury, and the retinas were collected from each rat for thickness measurements. Quantitative analysis of RGC survival was further determined using labeling with FluoroGold. RESULTS. The GlcN increased levels of O-GlcNAc in a dose-dependent manner in the RGCs treated with or without H2O2. The GlcN resulted in increased cell survival and reduced apoptosis in the RGCs under oxidative stress conditions. In the rat model of I/R injury, GlcN significantly protected against I/R-induced retinal thinning and suppressed the I/R-induced reductions in a-and b-wave amplitudes of the ERG. In terms of RGC survival, significant incremental density of RGCs was found in the I/R+GlcN group compared with the I/R group. Notably, the use of GlcN in the rat retina decreased apoptosis and the formation of reactive oxygen species (ROS) after I/R injury. We also found that mitogen-activated protein kinase signal pathways played a critical role in the GlcN-mediated attenuation of ROS-induced damage in vitro and I/R injury in vivo. CONCLUSIONS. Glucosamine treatment provides multiple levels of retinal protection, including antiapoptotic, anti-inflammatory, and antioxidative benefits. More research on the role of GlcN as a potential agent for the prevention and treatment of glaucoma is warranted.