Serotonin receptors are potential neuroprotective agents in degenerative diseases of the central nervous system. The protective effects of serotonin receptor (5-HT1A) agonists on the survival and function of retinal ganglion cells (RGCs) by regulating the release of the presynaptic neurotransmitter gamma-aminobutyric acid (GABA) were confirmed in our previous study of a chronic glaucoma rat model. However, the roles of excitatory amino acids and their interactions with the 5-HT1A receptor in glaucoma remain unknown. Here, we found that ocular hypertension increased glutamine synthetase (GS) and excitatory amino acid transporter 2 (EAAT2) expression in rat retinas. In addition, the high expression of GS and EAAT2 induced by glaucoma was downregulated by the 5-HT1A receptor agonist 8-OH-DPAT and the 5-HT1A receptor antagonist WAY-100635, respectively. Patch-clamp techniques were used to record glutamate receptor-mediated spontaneous and miniature glutamatergic excitatory post-synaptic currents (sEPSCs and mEPSCs) as well as L-glutamate-induced current in OFF-type and ON-type RGCs in rat retinal slices. Although there were no significant differences in the frequency and amplitude of sEPSC and mEPSC release between normal and glaucoma OFFand ON-type RGCs, exogenous 8-OH-DPAT administration specifically reduced the frequency, but not the amplitude, of sEPSC and mEPSC release in glaucoma OFF-type rather than ON-type RGCs; these effects were completely blocked by WAY-100635. In summary, 8-OH-DPAT decreases and increases GS and EAAT2 expression of glaucomatous retina, respectively, while decreasing sEPSC and mEPSC frequency. In contrast, WAY-100635 increases and decreases GS and EAAT2 expression of glaucomatous retina, respectively, while increasing sEPSC and mEPSC frequency. The reduction of glutamatergic presynaptic transmission by 8-OH-DPAT deactivates RGCs at the neural network level and reduces the excitotoxic damage in the pathological process of chronic glaucoma.
[1]Fudan Univ, Eye Inst, Eye & ENT Hosp, State Key Lab Med Neurobiol,Inst Brain Sci, Shanghai, Peoples R China;
[2]Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai Med Coll, Shanghai, Peoples R China;
[3]Shanghai Key Lab Visual Impairment & Restorat, Shanghai, Peoples R China;
[4]Fudan Univ, NHC Key Lab Myopia, Key Lab Myopia, Chinese Acad Med Sci, Shanghai, Peoples R China;
[5]Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol & Vis Sci, Shanghai, Peoples R China
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