DBA/2J mouse has been used as a model for spontaneous secondary glaucoma. Here, we investigated changes in expression of NMDA receptor (NMDAR) subunits and Cdk5/p35/NMDAR signaling in retinas of DBA/2J mice using Western blot technique. The protein levels of NR1 and NR2A subunits in retinas of DBA/2J mice at all ages (6–12 months) were not different from those in age-matched C57BL/6 mice. In contrast, the protein levels of NR2B subunits, in addition to age-dependent change, significantly increased with elevated intraocular pressure (IOP) in DBA/2J mice at 6 and 9 months as compared with age-matched controls. Moreover, expression of Cdk5, p35 and ratio of p-NR2AS1232/NR2A progressively increased with time in both strains, suggestive of activated Cdk5/p35 signaling pathway. However, the changes in these proteins were in the same levels in both strain mice, except a significant increase of p35 proteins at 6 months in DBA/2J mice. Meanwhile, the protein levels of Brn-3a, a retinal ganglion cell (RGC) maker, remarkably decreased at 9–12 months in DBA/2J mice, which was in parallel with the changes of NR2B expression. Our results suggest that elevated IOP-induced increase in expression of NR2B subunits of NMDARs may be involved in RGC degeneration of DBA/2J mice. 1. Introduction Glaucoma, the second leading cause of blindness worldwide, is a neurodegenerative disease characterized by apoptotic death of retinal ganglion cells (RGCs) and progressive visual field loss [1, 2], which is often associated with high intraocular pressure (IOP). Whilst the mechanisms of RGC death in glaucoma still remain a mystery, glutamate excitotoxicity triggered by overactivation of the N-methyl-D-aspartate receptors (NMDARs) may be a potential risk factor for retinal malfunction in glaucoma [3–5]. Indeed, delivery of NMDA channel blockers has been shown to effectively reduce RGC apoptosis in experimental rat glaucoma models [3, 6–8]. Our recent work also showed that cyclin-dependent kinase 5 (Cdk5)/p35-induced elevation of phosphorylated NR2A subunit of NMDARs at S1232 site (p-NR2AS1232) may contribute to RGC apoptotic death in experimental glaucomatous rats [9]. DBA/2J mouse is a spontaneous model of glaucomatous neurodegeneration, which develops a progressive form of pigmentary angle-closure glaucoma [10–13]. In these mice, IOPs become elevated by 6 months of age, and continued intraocular hypertension results in progressive RGC degeneration [12–17]. This is similar to what is observed in primary open angle glaucoma, which makes the DBA/2J mice represent a useful model to study
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