The knowledge about electrophysiological properties of retinal ganglion cells (RGCs), as well as modulation of these properties, is important not only for understanding the unique physiological functions of RGCs under normal conditions, but also for exploring the cellular mechanisms of retinal neurodegeneration diseases, such as glaucoma. In this paper, we reviewed the progress in electrophysiological studies of RGCs by using patch-clamp techniques, concerning the voltage-gated ion channels, the ligand-gated ion channels and the effects of neuromodulators on these channels.
Animals ; Electrophysiological Phenomena ; Humans ; Ion Channels ; physiology ; Patch-Clamp Techniques ; Retinal Ganglion Cells ; physiology

In the vertebrate retina, Müller cells are principal glial cells which stretch across the whole thickness of the retina and contact with the somata and processes of all retinal neurons, thus forming an anatomical and functional link between glial cells and retinal neurons. Numerous studies have shown that Müller cells express various neurotransmitter receptors, transporters, ion channels and enzymes that are relative to cellular activities. In addition, the cells also release factors, such as D-serine and glutamate etc., to regulate the neuron excitability. Therefore, retinal Müller cells may play more curious roles in addition to supporting the retinal neurons. The information exchange and interaction between Müller cells and neurons may regulate and maintain retinal neuronal functions. In the glaucomatous retina, Müller cells are reactivated (gliosis). Reactivated Müller cells undergo a variety of changes in cellular physiology, biochemistry and morphological features. Meanwhile, the reactivated Müller cells may produce and release cytotoxic factors, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and prostaglandin E2 (PGE2), thus involving in the induction of retinal ganglion cell apoptosis and death. Here, we reviewed the physiological properties of retinal Müller cells, and the functional changes of Müller cells in the glaucomatous retina.
Ependymoglial Cells ; pathology ; physiology ; Glaucoma ; physiopathology ; Humans ; Neurons ; physiology ; Retina ; cytology

Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels. The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques. The results showed that under current-clamped condition perfusing WIN55212-2 (WIN, 5 μmol/L), a CB1R agonist, did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs. In the presence of cocktail synaptic blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5 μmol/L) hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA). Phase-plane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN. However, WIN significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive of reduced rising and descending velocities of action potentials. The effects of WIN were reversed by co-application of SR141716, a CB1R selective antagonist. Moreover, WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked. These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.
Action Potentials ; Animals ; Benzoxazines ; pharmacology ; Evoked Potentials ; In Vitro Techniques ; Membrane Potentials ; Morpholines ; pharmacology ; Naphthalenes ; pharmacology ; Patch-Clamp Techniques ; Piperidines ; pharmacology ; Pyrazoles ; pharmacology ; Rats ; Receptor, Cannabinoid, CB1 ; physiology ; Retinal Ganglion Cells ; physiology

Glaucoma, the second leading cause of blindness, is a neurodegenerative disease characterized by optic nerve degeneration related to apoptotic death of retinal ganglion cells (RGCs). In the pathogenesis of RGC death following the onset of glaucoma, functional changes of glutamate receptors are commonly regarded as important risk factors. During the past several years, we have explored the mechanisms underlying RGC apoptosis and retinal Müller cell reactivation (gliosis) in a rat chronic ocular hypertension (COH) model. We demonstrated that elevated intraocular pressure in COH rats may induce changes of various signaling pathways, which are involved in RGC apoptosis by modulating glutamate NMDA and AMPA receptors. Moreover, we also demonstrated that over-activation of group I metabotropic glutamate receptors (mGluR I) by excessive extracellular glutamate in COH rats could contribute to Müller cell gliosis by suppressing Kir4.1 channels. In this review, incorporating our results, we discuss glutamate receptor- mediated RGC apoptosis and Müller cell gliosis in experimental glaucoma.
Animals ; Disease Models, Animal ; Glaucoma ; Ocular Hypertension ; Receptors, Glutamate ; Retina ; Retinal Ganglion Cells

Endocannabinoid receptor system is extensively expressed in the vertebrate retina. There are two types of cannabinoid receptors, CB1 and CB2. Activation of these two receptors by endocannabinoids N-arachidonoylethanolamide (anandamine, AEA) and 2-arachidonyl glycerol (2-AG) regulates multiple neuronal and glial ion channels, thus getting involved in retinal visual information processing. In this review, incorporating our results, we discuss the modulation of cannabinoid CB1 and CB2 receptors on retinal neuronal and glial ion channels and retinal synaptic transmission.

Microglia are involved in the inflammatory response and retinal ganglion cell damage in glaucoma. Here, we investigated how microglia proliferate and migrate in a mouse model of chronic ocular hypertension (COH). In COH retinas, the microglial proliferation that occurred was inhibited by the P2X7 receptor (P2X7R) blocker BBG or P2X7R knockout, but not by the P2X4R blocker 5-BDBD. Treatment of primary cultured microglia with BzATP, a P2X7R agonist, mimicked the effects of cell proliferation and migration in COH retinas through the intracellular MEK/ERK signaling pathway. Transwell migration assays showed that the P2X4R agonist CTP induced microglial migration, which was completely blocked by 5-BDBD. In vivo and in vitro experiments demonstrated that ATP, released from activated Müller cells through connexin43 hemichannels, acted on P2X7R to induce microglial proliferation, and acted on P2X4R/P2X7R (mainly P2X4R) to induce microglial migration. Our results suggest that inhibiting the interaction of Müller cells and microglia may attenuate microglial proliferation and migration in glaucoma.
Adenosine Triphosphate/pharmacology* ; Animals ; Cell Proliferation ; Glaucoma/metabolism* ; Mice ; Microglia/metabolism* ; Receptors, Purinergic P2X4/metabolism* ; Receptors, Purinergic P2X7/metabolism* ; Retinal Ganglion Cells/metabolism*

Ras-related C3 botulinum toxin substrate 1 (Rac1), a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity, is a key regulator of cytoskeletal reorganization in dendrites and spines. Here, we investigated whether and how Rac1 modulates synaptic transmission in mouse retinal ganglion cells (RGCs) using selective conditional knockout of Rac1 (Rac1-cKO). Rac1-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents, while glycine/GABA receptor-mediated miniature inhibitory postsynaptic currents were not affected. Although the total GluA1 protein level was increased in Rac1-cKO mice, its expression in the membrane component was unchanged. Rac1-cKO did not affect spine-like branch density in single dendrites, but significantly reduced the dendritic complexity, which resulted in a decrease in the total number of dendritic spine-like branches. These results suggest that Rac1 selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.