title: Enhanced expression of NR2B subunits of NMDA receptors in the inherited glaucomatous DBA/2J mouse retina.
abstract: 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-NR2A(S1232)/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.
authors.affiliation: Institutes of Brain Science, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China ; Institute of Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China ; State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China.
authors.forename: Ling-Dan
authors.initials: LD
authors.lastname: Dong
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Fang
authors.initials: F
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Jihong
authors.initials: J
authors.lastname: Wu
authors.forename: Yanying
authors.initials: Y
authors.lastname: Miao
authors.forename: Zhongfeng
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005901:Glaucoma / Q000378:metabolism* / Q000473:pathology; D007429:Intraocular Pressure; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012160:Retina / Q000378:metabolism* / Q000473:pathology
chemical_list: C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate