Mechanism of N-methyl-D-aspartate-induced retinal ganglion cell death

Excitotoxicity is a major cause of retinal ganglion cell (RGC) death during ischemic diseases such as vessel occlusion and diabetic retinopathy. However, the underlying mechanisms are not well understood. In this study, we found a novel and causative role for inflammatory leukocyte recruitment in NMDA-induced excitotoxicity. NMDA increased the expression of interleukin-1beta and TNF-alpha, and endothelial adhesion molecules, including ICAM-1, and induced leukocyte accumulation in the retinal vessels. Either systemic blockade of ICAM-1 in wild-type mice or the absence of CD18 in gene deficient (CD18-/-) mice significantly suppressed NMDA-induced leukocyte accumulation and RGC death. Furthermore, here we demonstrated the novel neuroprotective effect of statins against excitotoxicity-induced RGC death. Both statins and other anti-inflammatory agents may thus have therapeutic benefits in excitotoxicity-associated neurons. In this article, we demonstrate our previous data on NMDA-induced retinal damage and summarize the field of research on retinal excitotoxicity.