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Jeremy A. Murphy, Bryan A. Daniels, Balwantray C. Chauhan, William H. Baldridge; NMDA-induced Calcium Dynamics Are Altered In Retinas Of Adult Mice Deficient In The Neural Cell Adhesion Molecule (NCAM). Invest. Ophthalmol. Vis. Sci. 2012;53(14):6539.
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The onset of injury-induced retinal ganglion cell (RGC) loss occurs earlier in mice lacking (-/-) NCAM. Recent studies have shown that NMDA currents are greater in NCAM -/- hippocampal neurons. As elevated intracellular calcium concentration ([Ca2+]i) has been implicated in cell death associated with NMDA receptor-mediated excitotoxicity, we investigated whether NMDA-induced increases of [Ca2+]i are elevated in the retinas of NCAM -/- mice.
Retinal whole mounts were isolated from adult wild-type and NCAM -/- mice. RGCs were labeled with fura-2 Ca2+ indicator dye by either injecting dextran-conjugated dye into retinal wholemounts or by injecting dye salt into the vitreous of enucleated eyes followed by electroporation. The data reported represent fura-2 ratios ± SE.
In retinas labeled by the dextran injection technique, NMDA-induced increases of fura-2 ratios were significantly greater in NCAM -/- compared to WT retinas at 100 μM (by 106%; WT = 0.25 ± 0.03, NCAM -/- = 0.52 ± 0.03, P<0.001) or 500 μM NMDA (by 42%; WT 0.33 ± 0.03, NCAM -/- 0.47 ± 0.02, P<0.001). In retinas labeled by electroporation, [Ca2+]i was greater in cells of NCAM -/- retinas during exposure to 100 μM NMDA (by 26.8%; WT 0.26 ± 0.01, NCAM -/- 0.33 ± 0.01, P<0.001). There was no significant difference in fura-2 ratios between WT and NCAM -/- retinas in response to NMDA (10 and 100 μM) or kainic acid (KA, 25 μM).
These findings indicate that NMDA, but not KA, induced increases of [Ca2+]i are greater in RGCs lacking NCAM. This may suggest that the accelerated loss of RGCs in NCAM -/- animals is due, in part, to enhanced excitotoxicity.
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