Changes of vitreous amino acid content and retinal degeneration in DBA/2J mice during aging

Abstract

Abstract: : Purpose:The DBA/2J mouse spontaneously develops ocular hypertension and time–dependent retinal ganglion cell (RGC) loss. However, the mechanism of retinal degeneration in this animal model remains to be determined. The present study examines alterations of vitreal amino acid content, as well as cellular expression of glutamate receptors and transporters in the retina of DBA/2J mice during aging. Methods:Retinas were obtained from DBA/2J mice of different ages: 3, 6 and 11 months. C57BL6 mice were used as age–matched controls. Vitreal amino acid content was measured with HPLC. Immunohistochemistry and Western Blotting were performed on retinal cross–sections using specific antibodies against NMDA and AMPA receptors and glutamate transporters (GLAST, GLT–1, EAAC–1). Results: As measured with HPLC, the concentrations of Ser, Glu, Gln, Gly, Ala, Lys and Arg were significantly increased in DBA/2J mice at the age of 11 months comparing to younger stages and age–matched controls. Immunohistochemical experiments and Western Blots show that cellular expression of GLAST decreased markedly in the retina of 11 months old DBA/2J mice as compared to younger animals and age–matched controls. Cellular expression of GLT1 and EAAC1 did not change during aging in both control and DBA/2J mice. Conclusions: These findings indicate that changes of retinal amino acid content and enhanced glutamate neurotransmission might be causally related to the pathogenesis of retinal neurodegeneration in DBA/2J. Moreover, DBA/2J mice might be considered as an animal model to study excitotoxic retinal damage.

Keywords: retina: proximal (bipolar, amacrine, and ganglion cells) • vitreous • excitatory amino acid receptors