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Science (New York, N.Y.) Feb 2002Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the...
Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.
Topics: Animals; Axons; Biological Clocks; Circadian Rhythm; Dendrites; Isoquinolines; Kinetics; Light; Light Signal Transduction; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells; Rod Opsins; Suprachiasmatic Nucleus
PubMed: 11834835
DOI: 10.1126/science.1067262 -
Cells Jun 2021As part of the central nervous system, mammalian retinal ganglion cells (RGCs) lack significant regenerative capacity. Glaucoma causes progressive and irreversible... (Review)
Review
As part of the central nervous system, mammalian retinal ganglion cells (RGCs) lack significant regenerative capacity. Glaucoma causes progressive and irreversible vision loss by damaging RGCs and their axons, which compose the optic nerve. To functionally restore vision, lost RGCs must be replaced. Despite tremendous advancements in experimental models of optic neuropathy that have elucidated pathways to induce RGC neuroprotection and axon regeneration, obstacles to achieving functional visual recovery through RGC transplantation remain. Key challenges include poor graft survival, low donor neuron localization to the host retina, and inadequate dendritogenesis and synaptogenesis with afferent amacrine and bipolar cells. In this review, we summarize the current state of experimental RGC transplantation, and we propose a set of standard approaches to quantifying and reporting experimental outcomes in order to guide a collective effort to advance the field toward functional RGC replacement and optic nerve regeneration.
Topics: Animals; Humans; Nerve Regeneration; Neuroprotection; Regenerative Medicine; Retinal Ganglion Cells; Stem Cell Transplantation
PubMed: 34200991
DOI: 10.3390/cells10061426 -
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 -
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 -
European Journal of Pharmacology Sep 2016In clinical glaucoma, as well as in experimental models, the loss of retinal ganglion cells occurs by apoptosis. This final event is preceded by inflammatory responses... (Review)
Review
In clinical glaucoma, as well as in experimental models, the loss of retinal ganglion cells occurs by apoptosis. This final event is preceded by inflammatory responses involving the activation of innate and adaptive immunity, with retinal and optic nerve resident glial cells acting as major players. Here we review the current literature on the role of neuroinflammation in neurodegeneration, focusing on the inflammatory molecular mechanisms involved in the pathogenesis and progression of the optic neuropathy.
Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Glaucoma; Humans; Inflammation; Retinal Ganglion Cells
PubMed: 27044433
DOI: 10.1016/j.ejphar.2016.03.064 -
International Journal of Molecular... Mar 2020The retinal ganglion cells (RGCs) are the output cells of the retina into the brain. In mammals, these cells are not able to regenerate their axons after optic nerve... (Review)
Review
The retinal ganglion cells (RGCs) are the output cells of the retina into the brain. In mammals, these cells are not able to regenerate their axons after optic nerve injury, leaving the patients with optic neuropathies with permanent visual loss. An effective RGCs-directed therapy could provide a beneficial effect to prevent the progression of the disease. Axonal injury leads to the functional loss of RGCs and subsequently induces neuronal death, and axonal regeneration would be essential to restore the neuronal connectivity, and to reestablish the function of the visual system. The manipulation of several intrinsic and extrinsic factors has been proposed in order to stimulate axonal regeneration and functional repairing of axonal connections in the visual pathway. However, there is a missing point in the process since, until now, there is no therapeutic strategy directed to promote axonal regeneration of RGCs as a therapeutic approach for optic neuropathies.
Topics: Animals; Cell Differentiation; Cell- and Tissue-Based Therapy; Clinical Trials as Topic; Disease Progression; Humans; Neuroprotective Agents; Retinal Ganglion Cells
PubMed: 32218163
DOI: 10.3390/ijms21072262 -
Journal of Integrative Neuroscience Mar 2013The review deals with the morphology, physiology, topography, and central projections of direction-selective cells of the accessory optic system in vertebrates. (Review)
Review
The review deals with the morphology, physiology, topography, and central projections of direction-selective cells of the accessory optic system in vertebrates.
Topics: Animals; Humans; Motion Perception; Retinal Ganglion Cells; Visual Pathways
PubMed: 23621462
DOI: 10.1142/S0219635213300011 -
Optometry and Vision Science : Official... Aug 2014Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are a class of photoreceptors with established roles in non-image-forming processes.... (Review)
Review
Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are a class of photoreceptors with established roles in non-image-forming processes. Their contributions to image-forming vision may include the estimation of brightness. Animal models have been central for understanding the physiological mechanisms of ipRGC function and there is evidence of conservation of function across species. Intrinsically photosensitive retinal ganglion cells can be divided into five ganglion cell subtypes that show morphological and functional diversity. Research in humans has established that ipRGCs signal environmental irradiance to entrain the central body clock to the solar day for regulating circadian processes and sleep. In addition, ipRGCs mediate the pupil light reflex (PLR), making the PLR a readily accessible behavioral marker of ipRGC activity. Less is known about ipRGC function in retinal and optic nerve disease, with emerging research providing insight into their function in diabetes, retinitis pigmentosa, glaucoma, and hereditary optic neuropathy. We briefly review the anatomical distributions, projections, and basic physiological mechanisms of ipRGCs and their proposed and known functions in animals and humans with and without eye disease. We introduce a paradigm for differentiating inner and outer retinal inputs to the pupillary control pathway in retinal disease and apply this paradigm to patients with age-related macular degeneration (AMD). In these cases of patients with AMD, we provide the initial evidence that ipRGC function is altered and that the dysfunction is more pronounced in advanced disease. Our perspective is that with refined pupillometry paradigms, the PLR can be extended to AMD assessment as a tool for the measurement of inner and outer retinal dysfunction.
Topics: Animals; Humans; Light; Macular Degeneration; Reflex, Pupillary; Retinal Ganglion Cells; Rod Opsins
PubMed: 24879087
DOI: 10.1097/OPX.0000000000000284 -
Survey of Ophthalmology Apr 2003Neuroprotection is a therapeutic strategy directed at keeping retinal ganglion cells (RGCs) alive and functional. This article discusses three commonly asked questions... (Review)
Review
Neuroprotection is a therapeutic strategy directed at keeping retinal ganglion cells (RGCs) alive and functional. This article discusses three commonly asked questions about neuroprotection and attempts to answer them in the context of our current understanding of the pathophysiology of RGC loss in glaucomatous optic neuropathy.
Topics: Cytoprotection; Glaucoma; Humans; Neuroprotective Agents; Optic Nerve Diseases; Retinal Ganglion Cells
PubMed: 12852431
DOI: 10.1016/s0039-6257(03)00007-9 -
Cells Oct 2019The diffusion rate for proper nutrition of the inner retina depends mainly on four factors which are discussed in this review: 1. The diffusion distance between blood... (Review)
Review
The diffusion rate for proper nutrition of the inner retina depends mainly on four factors which are discussed in this review: 1. The diffusion distance between blood and retinal ganglion cells shows morphological variants in different mammalian species, namely a choroidal nutrition type, a retinal nutrition type, and a mixture of both types. 2. Low oxygen concentration levels in the inner retina force the diffusion of oxygen especially in the choroidal nutrition type. Other nutrients might be supplied by surrounding cells, mainly Müller cells. 3. Diffusion in the eye is influenced by the intraocular pressure, which is vital for the retinal ganglion cells but might also influence their proper function. Again, the nutrition types established might explain the differences in normal intraocular pressure levels among different species. 4. Temperature is a critical feature in the eye which has to be buffered to avoid neuronal damage. The most effective buffer system is the increased blood turnover in the choroid which has to be established in all species.
Topics: Animals; Choroid; Mammals; Models, Animal; Nutrients; Oxygen; Retina; Retinal Ganglion Cells; Species Specificity
PubMed: 31615137
DOI: 10.3390/cells8101254