Glutamate neurotoxicity is one of the causative factors leading to neural degeneration including retina. Inhibition of NMDA receptors has been shown neuroprotective effects. However, specifically inhibition of glycine subunit in NMDA receptors and its effects on retina neural protection has not been tested. In this study, using a glycine site-specific NMDA receptor antagonist, we investigated its neuroprotective effects on rat retinal ganglion cells (RGCs) from a transient ischemic injury and its possible underlying mechanisms. Following an ischemia/reperfusion injury the structural damages of rat retinas were assessed by an immunofluorescence method and the apoptosis of retinal neural cells was evaluated by using a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. The survived RGCs were labeled by retrograde manner and counted on whole-mounted retinas. In the presence of glycine site-specific NMDA receptor antagonist, the thickness of retina was sustained, especially in the inner nuclear layers compared with mock controls. While a significantly higher numbers of TUNEL-positive apoptotic cells and fewer of RGCs were observed in the retina without the glycine antagonist, indicating its strong protective roles. Some apoptotic factors such as Bax, Bcl-2, CAMK II, COX1, COX4, Caspase-3, and GRIN1 gene have been tested from retinal samples with or without the glycine antagonist. A significantly lower of expressions of Bax, CAMK II, COX1, COX4, Caspase-3, and GRIN1 have been shown in the retinas with the antagonist. Bcl-2/Bax ratio was significantly higher with the antagonist, suggested that the glycine site-specific NMDA receptor antagonist protecting RGC death might through inhibition of apoptotic signaling.
(c) 2010 Wiley-Liss, Inc.