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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 -
Progress in Retinal and Eye Research Jul 2023Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by a slow, progressive, and multifactorial degeneration of retinal ganglion cells... (Review)
Review
Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by a slow, progressive, and multifactorial degeneration of retinal ganglion cells (RGCs) and their axons, resulting in vision loss. Despite its high prevalence in individuals 60 years of age and older, the causing factors contributing to glaucoma progression are currently not well characterized. Intraocular pressure (IOP) is the only proven treatable risk factor. However, lowering IOP is insufficient for preventing disease progression. One of the significant interests in glaucoma pathogenesis is understanding the structural and functional impairment of mitochondria in RGCs and their axons and synapses. Glaucomatous risk factors such as IOP elevation, aging, genetic variation, neuroinflammation, neurotrophic factor deprivation, and vascular dysregulation, are potential inducers for mitochondrial dysfunction in glaucoma. Because oxidative phosphorylation stress-mediated mitochondrial dysfunction is associated with structural and functional impairment of mitochondria in glaucomatous RGCs, understanding the underlying mechanisms and relationship between structural and functional alterations in mitochondria would be beneficial to developing mitochondria-related neuroprotection in RGCs and their axons and synapses against glaucomatous neurodegeneration. Here, we review the current studies focusing on mitochondrial dynamics-based structural and functional alterations in the mitochondria of glaucomatous RGCs and therapeutic strategies to protect RGCs against glaucomatous neurodegeneration.
Topics: Humans; Retinal Ganglion Cells; Mitochondrial Dynamics; Glaucoma; Intraocular Pressure; Optic Nerve Diseases
PubMed: 36400670
DOI: 10.1016/j.preteyeres.2022.101136 -
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 -
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 -
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 -
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 -
The Yale Journal of Biology and Medicine Mar 2018The mammalian retina contains a small number of retinal ganglion cells that express melanopsin, a retinal based visual pigment, and generate a depolarizing response to... (Review)
Review
The mammalian retina contains a small number of retinal ganglion cells that express melanopsin, a retinal based visual pigment, and generate a depolarizing response to light in the absence of rod and cone driven synaptic input; hence they are referred to as intrinsically photosensitive retinal ganglion cells (ipRGCs). They have been shown to be comprised of a number of sub-types and to provide luminance information that participates primarily in a variety of non-imaging forming visual functions. Here I review what is currently known about the cascade of events that couple the photoisomerization of melanopsin to the opening of a non-selective cation channel. While these events conform in a general sense to the prevailing model for invertebrate phototransduction, in which visual pigment signals through a G protein of the G class and a phospholipase C cascade to open a TRPC type ion channel, none of the molecular elements in the melanopsin transduction process have been unequivocally identified. This has given rise to the possibility that the underlying mechanism responsible for intrinsic photosensitivity is not same in all ipRGC sub-types and to the recognition that signal transduction in ipRGCs is more complex than originally thought.
Topics: Animals; Humans; Light; Light Signal Transduction; Retinal Ganglion Cells
PubMed: 29599657
DOI: No ID Found -
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 -
Current Neuropharmacology 2018Retinal ganglion cells (RGCs) are the nervous retinal elements which connect the visual receptors to the brain forming the nervous visual system. Functional and/or... (Review)
Review
BACKGROUND
Retinal ganglion cells (RGCs) are the nervous retinal elements which connect the visual receptors to the brain forming the nervous visual system. Functional and/or morphological involvement of RGCs occurs in several ocular and neurological disorders and therefore these cells are targeted in neuroprotective strategies. Cytidine 5-diphosphocholine or Citicoline is an endogenous compound that acts in the biosynthesis of phospholipids of cell membranes and increases neurotransmitters' levels in the Central Nervous System. Experimental studies suggested the neuromodulator effect and the protective role of Citicoline on RGCs. This review aims to present evidence of the effects of Citicoline in experimental models of RGCs degeneration and in human neurodegenerative disorders involving RGCs.
METHODS
All published papers containing experimental or clinical studies about the effects of Citicoline on RGCs morphology and function were reviewed.
RESULTS
In rodent retinal cultures and animal models, Citicoline induces antiapoptotic effects, increases the dopamine retinal level, and counteracts retinal nerve fibers layer thinning. Human studies in neurodegenerative visual pathologies such as glaucoma or non-arteritic ischemic neuropathy showed a reduction of the RGCs impairment after Citicoline administration. By reducing the RGCs' dysfunction, a better neural conduction along the post-retinal visual pathways with an improvement of the visual field defects was observed.
CONCLUSION
Citicoline, with a solid history of experimental and clinical studies, could be considered a very promising molecule for neuroprotective strategies in those pathologies (i.e. Glaucoma) in which morpho-functional changes of RGCc occurs.
Topics: Animals; Cytidine Diphosphate Choline; Humans; Neurodegenerative Diseases; Neuroprotective Agents; Retinal Ganglion Cells
PubMed: 28676014
DOI: 10.2174/1570159X15666170703111729