Permissive role for mGlu1 metabotropic glutamate receptors in excitotoxic retinal degeneration.

摘要: Neuroprotection is an unmet need in eye disorders characterized by retinal ganglion cell (RGC) death, such as prematurity-induced degeneration, glaucoma, and age-related macular degeneration. In all these excitotoxicity a prominent component of neuronal damage, but clinical data discourage the development NMDA receptor antagonists neuroprotectants. Here, we show that activation mGlu1 metabotropic glutamate receptors largely contributes to excitotoxic degeneration RGCs. Mice at postnatal day 9 were challenged with toxic dose monosodium (MSG, 3g/kg), which caused death >70% Brn-3a+ Systemic administration negative allosteric modulator (NAM), JNJ16259685 (2.5mg/kg, s.c.), was protective against MSG-induced RGC death. This treatment did not cause changes motor behavior pups. We also injected MSG crv4 mice, lack because recessive mutation gene encoding receptor. whereas it retained its activity their wild-type littermates. These findings demonstrate play key role RGCs, encourage study NAMs models neurodegeneration.