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Neuron Oct 2019The mammalian visual system encodes information over a remarkable breadth of spatiotemporal scales and light intensities. This performance originates with its complement... (Review)
Review
The mammalian visual system encodes information over a remarkable breadth of spatiotemporal scales and light intensities. This performance originates with its complement of photoreceptors: the classic rods and cones, as well as the intrinsically photosensitive retinal ganglion cells (ipRGCs). IpRGCs capture light with a G-protein-coupled receptor called melanopsin, depolarize like photoreceptors of invertebrates such as Drosophila, discharge electrical spikes, and innervate dozens of brain areas to influence physiology, behavior, perception, and mood. Several visual responses rely on melanopsin to be sustained and maximal. Some require ipRGCs to occur at all. IpRGCs fulfill their roles using mechanisms that include an unusual conformation of the melanopsin protein, an extraordinarily slow phototransduction cascade, divisions of labor even among cells of a morphological type, and unorthodox configurations of circuitry. The study of ipRGCs has yielded insight into general topics that include photoreceptor evolution, cellular diversity, and the steps from biophysical mechanisms to behavior.
Topics: Action Potentials; Animals; Circadian Rhythm; Humans; Light; Light Signal Transduction; Mice; Reflex, Pupillary; Retinal Ganglion Cells; Rod Opsins; Vision, Ocular
PubMed: 31647894
DOI: 10.1016/j.neuron.2019.07.016 -
Nutrients Jan 2022Glaucoma is one of the leading causes of irreversible blindness. It is generally caused by increased intraocular pressure, which results in damage of the optic nerve and... (Review)
Review
Glaucoma is one of the leading causes of irreversible blindness. It is generally caused by increased intraocular pressure, which results in damage of the optic nerve and retinal ganglion cells, ultimately leading to visual field dysfunction. However, even with the use of intraocular pressure-lowering eye drops, the disease still progresses in some patients. In addition to mechanical and vascular dysfunctions of the eye, oxidative stress, neuroinflammation and excitotoxicity have also been implicated in the pathogenesis of glaucoma. Hence, the use of natural products with antioxidant and anti-inflammatory properties may represent an alternative approach for glaucoma treatment. The present review highlights recent preclinical and clinical studies on various natural products shown to possess neuroprotective properties for retinal ganglion cells, which thereby may be effective in the treatment of glaucoma. Intraocular pressure can be reduced by baicalein, forskolin, marijuana, ginsenoside, resveratrol and hesperidin. Alternatively, , , , , saffron, curcumin, caffeine, anthocyanin, coenzyme Q10 and vitamins B3 and D have shown neuroprotective effects on retinal ganglion cells via various mechanisms, especially antioxidant, anti-inflammatory and anti-apoptosis mechanisms. Extensive studies are still required in the future to ensure natural products' efficacy and safety to serve as an alternative therapy for glaucoma.
Topics: Biological Products; Glaucoma; Humans; Intraocular Pressure; Neuroprotection; Retinal Ganglion Cells
PubMed: 35276895
DOI: 10.3390/nu14030534 -
Cell Sep 2018Light exerts a range of powerful biological effects beyond image vision, including mood and learning regulation. While the source of photic information affecting mood...
Light exerts a range of powerful biological effects beyond image vision, including mood and learning regulation. While the source of photic information affecting mood and cognitive functions is well established, viz. intrinsically photosensitive retinal ganglion cells (ipRGCs), the central mediators are unknown. Here, we reveal that the direct effects of light on learning and mood utilize distinct ipRGC output streams. ipRGCs that project to the suprachiasmatic nucleus (SCN) mediate the effects of light on learning, independently of the SCN's pacemaker function. Mood regulation by light, on the other hand, requires an SCN-independent pathway linking ipRGCs to a previously unrecognized thalamic region, termed perihabenular nucleus (PHb). The PHb is integrated in a distinctive circuitry with mood-regulating centers and is both necessary and sufficient for driving the effects of light on affective behavior. Together, these results provide new insights into the neural basis required for light to influence mood and learning.
Topics: Affect; Animals; Brain; Circadian Rhythm; Learning; Light; Mice; Mice, Inbred C57BL; Phototherapy; Retina; Retinal Ganglion Cells; Signal Transduction; Suprachiasmatic Nucleus; Vision, Ocular; Visual Pathways; Visual Perception
PubMed: 30173913
DOI: 10.1016/j.cell.2018.08.004 -
International Journal of Molecular... Apr 2018Glaucoma is one of the leading causes of irreversible visual loss, which has been estimated to affect 3.5% of those over 40 years old and projected to affect a total of... (Review)
Review
Glaucoma is one of the leading causes of irreversible visual loss, which has been estimated to affect 3.5% of those over 40 years old and projected to affect a total of 112 million people by 2040. Such a dramatic increase in affected patients demonstrates the need for continual improvement in the way we diagnose and treat this condition. Annexin A5 is a 36 kDa protein that is ubiquitously expressed in humans and is studied as an indicator of apoptosis in several fields. This molecule has a high calcium-dependent affinity for phosphatidylserine, a cell membrane phospholipid externalized to the outer cell membrane in early apoptosis. The DARC (Detection of Apoptosing Retinal Cells) project uses fluorescently-labelled annexin A5 to assess glaucomatous degeneration, the inherent process of which is the apoptosis of retinal ganglion cells. Furthermore, this project has conducted investigation of the retinal apoptosis in the neurodegenerative conditions of the eye and brain. In this present study, we summarized the use of annexin A5 as a marker of apoptosis in the eye. We also relayed the progress of the DARC project, developing real-time imaging of retinal ganglion cell apoptosis in vivo from the experimental models of disease and identifying mechanisms underlying neurodegeneration and its treatments, which has been applied to the first human clinical trials. DARC has potential as a biomarker in neurodegeneration, especially in the research of novel treatments, and could be a useful tool for the diagnosis and monitoring of glaucoma.
Topics: Animals; Annexin A5; Annexins; Apoptosis; Biomarkers; Glaucoma; Humans; Retina; Retinal Ganglion Cells
PubMed: 29673196
DOI: 10.3390/ijms19041218 -
Survey of Ophthalmology 2021Glaucoma is an optic neuropathy characterized by well-defined optic disc morphological changes (i.e., cup enlargement, neuroretinal border thinning, and notching,... (Review)
Review
Glaucoma is an optic neuropathy characterized by well-defined optic disc morphological changes (i.e., cup enlargement, neuroretinal border thinning, and notching, papillary vessel modifications) consequent to retinal ganglion cell loss, axonal degeneration, and lamina cribrosa remodeling. These modifications tend to be progressive and are the main cause of functional damage in glaucoma. Despite the latest findings about the pathophysiology of the disease, the exact trigger mechanisms and the mechanism of degeneration of retinal ganglion cells and their axons have not been completely elucidated. Neuroinflammation may play a role in both the development and the progression of the disease as a result of its effects on retinal environment and retinal ganglion cells. We summarize the latest findings about neuroinflammation in glaucoma and examine the connection between risk factors, neuroinflammation, and retinal ganglion cell degeneration.
Topics: Glaucoma; Humans; Neuroinflammatory Diseases; Optic Disk; Optic Nerve Diseases; Retinal Ganglion Cells
PubMed: 33582161
DOI: 10.1016/j.survophthal.2021.02.003 -
Cells Nov 2020The main goal of this thematic issue was to bring both original research papers and reviews together to provide an insight into the rather broad topic of molecular...
The main goal of this thematic issue was to bring both original research papers and reviews together to provide an insight into the rather broad topic of molecular biology of retinal ganglion cells (RGCs) [...].
Topics: Humans; Molecular Biology; Optic Nerve Diseases; Research; Retinal Ganglion Cells
PubMed: 33203148
DOI: 10.3390/cells9112483 -
Frontiers in Neural Circuits 2016Spontaneous activity patterns propagate through many parts of the developing nervous system and shape the wiring of emerging circuits. Prior to vision, waves of activity... (Review)
Review
Spontaneous activity patterns propagate through many parts of the developing nervous system and shape the wiring of emerging circuits. Prior to vision, waves of activity originating in the retina propagate through the lateral geniculate nucleus (LGN) of the thalamus to primary visual cortex (V1). Retinal waves have been shown to instruct the wiring of ganglion cell axons in LGN and of thalamocortical axons in V1 via correlation-based plasticity rules. Across species, retinal waves mature in three stereotypic stages (I-III), in which distinct circuit mechanisms give rise to unique activity patterns that serve specific functions in visual system refinement. Here, I review insights into the patterns, mechanisms, and functions of stage III retinal waves, which rely on glutamatergic signaling. As glutamatergic waves spread across the retina, neighboring ganglion cells with opposite light responses (ON vs. OFF) are activated sequentially. Recent studies identified lateral excitatory networks in the inner retina that generate and propagate glutamatergic waves, and vertical inhibitory networks that desynchronize the activity of ON and OFF cells in the wavefront. Stage III wave activity patterns may help segregate axons of ON and OFF ganglion cells in the LGN, and could contribute to the emergence of orientation selectivity in V1.
Topics: Animals; Geniculate Bodies; Glutamates; Nerve Net; Retinal Ganglion Cells; Signal Transduction; Visual Pathways
PubMed: 27242446
DOI: 10.3389/fncir.2016.00038 -
ELife Nov 2023Neurons that transmit information from the retina to other parts of the brain are more affected by anesthesia than previously thought.
Neurons that transmit information from the retina to other parts of the brain are more affected by anesthesia than previously thought.
Topics: Retinal Ganglion Cells; Retina; Sensory Receptor Cells; Sleep
PubMed: 37947192
DOI: 10.7554/eLife.93339 -
International Journal of Molecular... Jan 2020Across all species, retinal ganglion cells (RGCs) are the first retinal neurons generated during development, followed by the other retinal cell types. How are retinal... (Review)
Review
Across all species, retinal ganglion cells (RGCs) are the first retinal neurons generated during development, followed by the other retinal cell types. How are retinal progenitor cells (RPCs) able to produce these cell types in a specific and timely order? Here, we will review the different models of retinal neurogenesis proposed over the last decades as well as the extrinsic and intrinsic factors controlling it. We will then focus on the molecular mechanisms, especially the cascade of transcription factors that regulate, more specifically, RGC fate. We will also comment on the recent discovery that the ciliary marginal zone is a new stem cell niche in mice contributing to retinal neurogenesis, especially to the generation of ipsilateral RGCs. Furthermore, RGCs are composed of many different subtypes that are anatomically, physiologically, functionally, and molecularly defined. We will summarize the different classifications of RGC subtypes and will recapitulate the specification of some of them and describe how a genetic disease such as albinism affects neurogenesis, resulting in profound visual deficits.
Topics: Albinism; Animals; Fibroblast Growth Factors; Hedgehog Proteins; Humans; Neurogenesis; Retina; Retinal Ganglion Cells; Transcription Factors
PubMed: 31936811
DOI: 10.3390/ijms21020451 -
Annual Review of Vision Science Sep 2022Retinal circuits transform the pixel representation of photoreceptors into the feature representations of ganglion cells, whose axons transmit these representations to... (Review)
Review
Retinal circuits transform the pixel representation of photoreceptors into the feature representations of ganglion cells, whose axons transmit these representations to the brain. Functional, morphological, and transcriptomic surveys have identified more than 40 retinal ganglion cell (RGC) types in mice. RGCs extract features of varying complexity; some simply signal local differences in brightness (i.e., luminance contrast), whereas others detect specific motion trajectories. To understand the retina, we need to know how retinal circuits give rise to the diverse RGC feature representations. A catalog of the RGC feature set, in turn, is fundamental to understanding visual processing in the brain. Anterograde tracing indicates that RGCs innervate more than 50 areas in the mouse brain. Current maps connecting RGC types to brain areas are rudimentary, as is our understanding of how retinal signals are transformed downstream to guide behavior. In this article, I review the feature selectivities of mouse RGCs, how they arise, and how they are utilized downstream. Not only is knowledge of the behavioral purpose of RGC signals critical for understanding the retinal contributions to vision; it can also guide us to the most relevant areas of visual feature space.
Topics: Animals; Axons; Brain; Mice; Retina; Retinal Ganglion Cells; Vision, Ocular
PubMed: 35385673
DOI: 10.1146/annurev-vision-100419-112009