advertisement
Abstract #86290 Published in IGR 21-2
Group II metabotropic glutamate receptor agonist promotes retinal ganglion cell survival by reducing neuronal excitotoxicity in a rat chronic ocular hypertension model
Li Q; Jin R; Zhang S; Sun X; Wu JNeuropharmacology 2020; 170: 108016
Glaucoma, the second leading cause of irreversible blindness worldwide, is characterized by the selective death of retinal ganglion cells (RGCs). The group II metabotropic glutamate receptor (mGluR II) activation has been linked to RGC survival, however, the mechanism by which it promotes neuronal survival remains poorly defined. In the present work, we show that extracellular application of LY341495, an mGluR II antagonist could increase the RGC firing frequency, suggesting that activation of mGluR II by endogenously released glutamate could modulate RGC excitability. LY354740, an mGluR II agonist, significantly decreased RGC excitability and the reduced presynaptic excitatory inputs and post-synaptic Ca2+-permeable currents mediated the LY354740-induced effects. By using a well-characterized in vivo male Sprague-Dawley rat glaucoma model, we further demonstrate that in the early stage of experimental glaucoma, the expression of mGluR II dimer-formed protein was significantly reduced, and pre-activation of mGluR II by intravitreal injection of LY354740 before establishment of the glaucoma model could effectively reduce excitatory inputs, thereby reversing hyperexcitability induced by elevated intraocular pressure. Furthermore, LY354740 could increase the expression level of brain-derived neurotrophic factor in the glaucomatous retinas, further protecting RGCs. Our study indicates that the abnormal expression of mGluR II may accelerate RGC apoptosis in glaucoma, and demonstrates that mGluR II agonist LY354740 can be used as a novel method to counter RGC apoptosis in glaucoma.
Eye Institute, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, 200031, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, 200031, China; NHC Key Laboratory of Myopia (Fudan University), Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, 200031, China; Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China.
Full articleClassification:
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.8 Pharmacology (Part of: 3 Laboratory methods)
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
