μ-Opioid Receptor Activation Directly Modulates Intrinsically Photosensitive Retinal Ganglion Cells

Neurons in both vertebrate and invertebrate eyes are organized in regular arrays. Although much is known about the mechanisms involved in the formation of the regular arrays of neurons found in invertebrate eyes, much less is known about the mechanisms of formation of neuronal mosaics in the vertebrate eye. The purpose of these studies was to determine the cellular mechanisms that pattern the first neurons in vertebrate retina, the retinal ganglion cells. We have found that the ganglion cells in the chick retina develop as a patterned array that spreads from the central to peripheral retina as a wave front of differentiation. The onset of ganglion cell differentiation keeps pace with overall retinal growth; however, there is no clear cell cycle synchronization at the front of differentiation of the first ganglion cells. The differentiation of ganglion cells is not dependent on signals from previously formed ganglion cells, since isolation of the peripheral retina by as much as 400 μm from the front of ganglion cell differentiation does not prevent new ganglion cells from developing. Consistent with previous studies, blocking FGF receptor activation with a specific inhibitor to the FGFRs retards the movement of the front of ganglion cell differentiation, while application of exogenous FGF1 causes the precocious development of ganglion cells in peripheral retina. Our observations, taken together with those of previous studies, support a role for FGFs and FGF receptor activation in the initial development of retinal ganglion cells from the undifferentiated neuroepithelium peripheral to the expanding wave front of differentiation.

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Role of the ETB receptor in retinal ganglion cell death in glaucomaThis article is one of a selection of papers published in the special issue (part 1 of 2) on Forefronts in Endothelin.

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y08-040 ◽

2008 ◽

Vol 86 (6) ◽

pp. 380-393 ◽

Cited By ~ 39

Author(s):

Raghu R. Krishnamoorthy ◽

Vidhya R. Rao ◽

Rachel Dauphin ◽

Ganesh Prasanna ◽

Christina Johnson ◽

...

Keyword(s):

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Receptor Activation ◽

Receptor Expression ◽

Glaucomatous Optic Neuropathy ◽

Retinal Ganglion ◽

Flow Cytometric ◽

Retinal Ganglion Cell Death ◽

Etb Receptor ◽

Ganglion Cell Death

Recent observations suggest that the vasoactive peptide endothelin-1 (ET-1) may be an important contributor to the etiology of glaucoma. ET-1 administration has been shown to produce optic nerve axonal loss and apoptosis of retinal ganglion cells. Ocular ET-1 levels are elevated in aqueous humor in response to elevated intraocular pressure both in glaucoma patients and in animal models of glaucoma; however, the precise mechanisms by which ET-1 mediates glaucomatous optic neuropathy are not clear. Presently we report that ET-1-mediated apoptosis was markedly attenuated in ETB receptor-deficient rats, suggesting a key role for ETB receptors in apoptosis of retinal ganglion cells by ET-1 treatment. Using virally transformed rat retinal ganglion cells (RGC-5 cells), we found that ET-1 (100 nmol/L) treatment produced apoptotic changes in these cells that was determined by flow cytometric analyses, release of mitochondrial cytochrome c to the cytosol, and increased phosphorylation of c-Jun N-terminal kinase. Pretreatment with the ETB-receptor antagonist BQ788 (1 μmol/L) was able to significantly attenuate ET-1-mediated apoptosis in RGC-5 cells. ET-1-mediated apoptotic changes in RGC-5 cells were associated with ETB-receptor activation and were accompanied by a significant upregulation of ETB-receptor expression. These studies suggest that ocular ET-1 acts through ETB receptors to mediate apoptosis of retinal ganglion cells, a key event in glaucoma and related optic neuropathies.

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Inhibition of Adult Rat Retinal Ganglion Cells by D1-Type Dopamine Receptor Activation

Journal of Neuroscience ◽

10.1523/jneurosci.3827-09.2009 ◽

2009 ◽

Vol 29 (47) ◽

pp. 15001-15016 ◽

Cited By ~ 21

Author(s):

Y. Hayashida ◽

C. V. Rodriguez ◽

G. Ogata ◽

G. J. Partida ◽

H. Oi ◽

...

Keyword(s):

Dopamine Receptor ◽

Retinal Ganglion Cells ◽

Ganglion Cells ◽

Receptor Activation ◽

Retinal Ganglion ◽

Adult Rat

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Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells

Visual Neuroscience ◽

10.1017/s0952523811000198 ◽

2011 ◽

Vol 28 (5) ◽

pp. 393-402 ◽

Cited By ~ 22

Author(s):

T. P. MIDDLETON ◽

D. A. PROTTI

Keyword(s):

Synaptic Transmission ◽

Retinal Ganglion Cells ◽

Cannabinoid Receptor ◽

Ganglion Cells ◽

Cell Voltage ◽

Receptor Activation ◽

Synaptic Activity ◽

Retinal Cell ◽

Retinal Ganglion ◽

Retinal Processing

AbstractThe endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14–P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.

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