Animals ; Embryo, Mammalian ; Humans ; Photoreceptor Cells, Vertebrate ; metabolism ; physiology ; Retinal Ganglion Cells ; metabolism ; physiology ; Retinal Pigments ; metabolism

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 vertebrate visual system, information is firstly processed in retina. With the development of the multi-electrode recording technique, concerted activity has been extensively observed in retinal ganglion cells of different species. However, the role of concerted activity in visual information processing is still unclear and under debating. This article reviews the recent studies focused on concerted activity among retinal ganglion cells, discussing the issues about its category, detection and physiological function.
Animals ; Cell Communication ; physiology ; Humans ; Photic Stimulation ; Retina ; physiology ; Retinal Ganglion Cells ; physiology ; Visual Pathways ; physiology ; Visual Perception ; physiology

In order to elucidate in vivo neuronal cell death in the retina, and involvement of NF-kappa B in this process, we studied the degeneration of retinal ganglion cells (RGCs) and the activation of NF-kappa B after transection of the optic nerve of adult rat at 5 mm from the eyeball. The morphology of dying ganglion cells in the retinal ganglion cell layer was observed by light and electron microscopy, the activation of NF-kappa B was investigated immunohistochemically. Seven and 14 days post-axotomy, dying cells contained pyknotic nuclei. The death of retinal ganglion cells involved apoptosis, activation of NF-kappa B (p50 and p65) was prominent in a time dependent manner. We observed axotomy-induced NF-kappa B activation, which may mediate apoptosis of retinal ganglion cells.
Animal ; Apoptosis/physiology ; Axotomy ; Immunohistochemistry ; Male ; Microscopy, Electron ; NF-kappa B/biosynthesis* ; Optic Nerve/surgery ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells/ultrastructure ; Retinal Ganglion Cells/pathology* ; Retinal Ganglion Cells/metabolism ; Substances: NF-kappa B

Apoptosis ; Humans ; Nerve Regeneration ; Neuroprotective Agents ; pharmacology ; Retinal Ganglion Cells ; drug effects ; physiology ; Stem Cell Transplantation

Correlated firings among neurons have been extensively investigated; however, previous studies on retinal ganglion cell (RGC) population activities were mainly based on analyzing the correlated activities between the entire spike trains. In the present study, the correlation properties were explored based on burst-like activities and solitary spikes separately. The results indicate that: (1) burst-like activities were more correlated with other neurons' activities; (2) burst-like spikes correlated with their neighboring neurons represented a smaller receptive field than that of correlated solitary spikes. These results suggest that correlated burst-like spikes should be more efficient in signal transmission, and could encode more detailed spatial information.
Action Potentials ; Animals ; Computer Simulation ; Darkness ; Electrophysiology ; In Vitro Techniques ; Light ; Patch-Clamp Techniques ; Postsynaptic Potential Summation ; Rana catesbeiana ; physiology ; surgery ; Retina ; physiology ; Retinal Ganglion Cells ; physiology ; Retinal Neurons ; physiology ; Signal Transduction

OBJECTIVE: To investigate the therapeutic effect of Epothilone D on traumatic optic neuropathy (TON) in rats. METHODS: Forty-two SD rats were randomized to receive intraperitoneal injection of 1.0 mg/kg Epothilone D or DMSO (control) every 3 days until day 28, and rat models of TON were established on the second day after the first administration. On days 3, 7, and 28, examination of flash visual evoked potentials (FVEP), immunofluorescence staining and Western blotting were performed to examine the visual pathway features, number of retinal ganglion cells (RGCs), GAP43 expression level in damaged axons, and changes of Tau and pTau-396/404 in the retina and optic nerve. RESULTS: In Epothilone D treatment group, RGC loss rate was significantly decreased by 19.12% (P=0.032) on day 3 and by 22.67% (P=0.042) on day 28 as compared with the rats in the control group, but FVEP examination failed to show physiological improvement in the visual pathway on day 28 in terms of the relative latency of N2 wave (P=0.236) and relative amplitude attenuation of P2-N2 wave (P=0.441). The total Tau content in the retina of the treatment group was significantly increased compared with that in the control group on day 3 (P < 0.001), showing a consistent change with ptau-396/404 level. In the optic nerve axons, the total Tau level in the treatment group was significantly lower than that in the control group on day 7 (P=0.002), but the changes of the total Tau and pTau-396/404 level did not show an obvious correlation. Epothilone D induced persistent expression of GAP43 in the damaged axons, detectable even on day 28 of the experiment. CONCLUSION Epothilone D treatment can protect against TON in rats by promoting the survival of injured RGCs, enhancing Tau content in the surviving RGCs, reducing Tau accumulation in injured axons, and stimulating sustained regeneration of axons.
Animals ; Disease Models, Animal ; Epothilones ; Evoked Potentials, Visual ; Nerve Regeneration/physiology* ; Optic Nerve Injuries/metabolism* ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells/physiology*

Objective To assess the in vivo dynamic blood flow features of posterior optic nerve head (ONH) in rat model of nonarteritic anterior ischemic optic neuropathy (rNAION). Methods rNAION was established with Rose Bengal and argon green laser in Sprague-Dawley rats. Fundus photography and fundus fluorescein angiography (FFA) were performed to assess the dynamic changes of optic disc in morphology in 90 days and in blood perfusion in 3 hours after the induction of disease. Histological examinations were performed to evaluate the success of modeling. The dynamic blood flow kinetics of posterior ONH in rNAION were measured by Laser Doppler Flowmetry (LDF) on the day 3, 7, 14, 21, and 40 after the disease induction. One-way ANOVA, Student's t-test and Bonferroni adjustment were used for multiple comparisons of kinetic measurements of blood flow. Results Optic disc edema and subsequent resolution associated with the development of optic disc pallor were observed in rNAION. FFA showed that the optic disc was hypofluorescence in the early phase and hyperfluorescence in the late phase. Histological studies suggested edema and loosened tissues of ONH, loss of retinal ganglion cells (RGCs), optic nerve substance and gliosis. Compared to the naive rats, the blood flow kinetics of posterior ONH in rNAION significant reduced at each time point after modeling (F=175.06, P<0.0001). The reductions were specifically remarkable in 14 days after the disease induction (All P<0.01). Conclusions Continuous blood perfusion reduction was found in rNAION, with significant alteration in 14 days after disease induction. Our results provided important information for understanding the hemodynamic changes in rNAION.
Animals ; Disease Models, Animal ; Fluorescein Angiography ; Hemodynamics ; physiology ; Humans ; Male ; Optic Disk ; pathology ; physiopathology ; Optic Neuropathy, Ischemic ; pathology ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Retinal Ganglion Cells ; physiology

BACKGROUNDGlaucoma is a progressive optic neuropathy characterized by degeneration of neurons due to loss of retinal ganglion cells (RGCs). High intraocular pressure (HIOP), the main risk factor, causes the optic nerve damage. However, the precise mechanism of HIOP-induced RGC death is not yet completely understood. This study was conducted to determine apoptosis of RGC-5 cells induced by elevated hydrostatic pressures, explore whether laminin is associated with apoptosis under pressure, whether laminin can protect RGCs from apoptosis and affirm the mechanism that regulates the process of RGCs survival.

METHODSRGC-5 cells were exposed to 0, 20, 40, and 60 mmHg in a pressurized incubator for 6, 12, and 24 h, respectively. The effect of elevated hydrostatic pressure on RGC-5 cells was measured by Annexin V-fluorescein isothiocyanate/propidium iodide staining, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and Western blotting of cleaved caspase-3 protein. Location and expression of laminin were detected by immunofluorescence. The expression of β1-integrin, phosphorylation of focal adhesion kinase (FAK) and protein kinase B (PKB, or AKT) were investigated with real-time polymerase chain reaction and Western blotting analysis.

RESULTSElevated hydrostatic pressure induced apoptosis in cultured RGC-5 cells. Pressure with 40 mmHg for 24 h induced a maximum apoptosis. Laminin was declined in RGC-5 cells after exposing to 40 mmHg for 24 h. After pretreating with laminin, RGC-5 cells survived from elevated pressure. Furthermore, β1-integrin and phosphorylation of FAK and AKT were increased compared to 40 mmHg group.

CONCLUSIONSThe data show apoptosis tendency of RGC-5 cells with elevated hydrostatic pressure. Laminin can protect RGC-5 cells against high pressure via β1-integrin/FAK/AKT signaling pathway. These results suggest that the decreased laminin of RGC-5 cells might be responsible for apoptosis induced by elevated hydrostatic pressure, and laminin or activating β1-integrin/FAK/AKT pathway might be potential treatments to prevent RGC loss in glaucomatous optic neuropathy.

Apoptosis ; Cells, Cultured ; Focal Adhesion Protein-Tyrosine Kinases ; physiology ; Humans ; Hydrostatic Pressure ; Integrin beta1 ; physiology ; Intraocular Pressure ; Laminin ; physiology ; Proto-Oncogene Proteins c-akt ; physiology ; Retinal Ganglion Cells ; physiology ; Up-Regulation

OBJECTIVETo review the updated research on neuroprotection in glaucoma, and summarize the potential agents investigated so far.

DATA SOURCESThe data in this review were collected from PubMed and Google Scholar databases published in English up to September 2012, with keywords including glaucoma, neuroprotection, and retinal ganglion cells, both alone and in combination. Publications from the past ten years were selected, but important older articles were not excluded.

STUDY SELECTIONArticles about neuroprotection in glaucoma were selected and reviewed, and those that are cited in articles identified by this search strategy and judged relevant to this review were also included.

RESULTSAlthough lowering the intraocular pressure is the only therapy approved as being effective in the treatment of glaucoma, increasing numbers of studies have discovered various mechanisms of retinal ganglion cells death in the glaucoma and relevant neuroprotective strategies. These strategies target neurotrophic factor deprivation, excitotoxic damage, oxidative stress, mitochondrial dysfunction, inflammation, activation of intrinsic and extrinsic apoptotic signals, ischemia, and protein misfolding. Exploring the mechanism of axonal transport failure, synaptic dysfunction, the glial system in glaucoma, and stem cell used in glaucoma constitute promising research areas of the future.

CONCLUSIONSNeuroprotective strategies continue to be refined, and future deep investment in researching the pathogenesis of glaucoma may provide novel and practical neuroprotection tactics. Establishing a system to assess the effects of neuroprotection treatments may further facilitate this research.

Apoptosis ; Axonal Transport ; Brain-Derived Neurotrophic Factor ; physiology ; Ciliary Neurotrophic Factor ; physiology ; Glaucoma ; etiology ; therapy ; Humans ; Mitochondria ; physiology ; Neuroprotective Agents ; therapeutic use ; Oxidative Stress ; Protein Folding ; Receptors, N-Methyl-D-Aspartate ; physiology ; Retinal Ganglion Cells ; physiology