To identify and determine the function of the proteins associated with the death of retinal ganglion cells (RGCs) in DBA/2J mice, an animal model of glaucoma, retinas of DBA/2J mice, were analyzed by proteomics at 5-, 7-, and 11-months-of-age. The proteins showing significant alterations were selected for identification by MS and 18 proteins were differentially expressed and the identified proteins included cell membrane receptors and proteins associated with intracellular signaling pathways. Among of identified proteins, the expression of Integrin beta7 at 7-months-of-age was decreased by about 89% of that at 5-months-of-age. Integrin beta7 was expressed in the RGCs. The effect of glutamate toxicity on the expression pattern of Integrin beta7 in a RGC line was also investigated and the glutamate-induced death of RGC was inhibited by the RNA knockdown of Integrin beta7. Our data showed also that the expression of 18 proteins in the DBA/2J was significantly altered in DBA2 mice and down-regulation of Integrin beta7 may have a protective effect on glutamate-induced death of RGCs.