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International Journal of Molecular... Mar 2023Light is a fundamental aspect of our lives, being involved in the regulation of numerous processes in our body. While blue light has always existed in nature, with the... (Review)
Review
Light is a fundamental aspect of our lives, being involved in the regulation of numerous processes in our body. While blue light has always existed in nature, with the ever-growing number of electronic devices that make use of short wavelength (blue) light, the human retina has seen increased exposure to it. Because it is at the high-energy end of the visible spectrum, many authors have investigated the theoretical harmful effects that it poses to the human retina and, more recently, the human body, given the discovery and characterization of the intrinsically photosensitive retinal ganglion cells. Many approaches have been explored, with the focus shifting throughout the years from examining classic ophthalmological parameters, such as visual acuity, and contrast sensitivity to more complex ones seen on electrophysiological assays and optical coherence tomographies. The current study aims to gather the most recent relevant data, reveal encountered pitfalls, and suggest future directions for studies regarding local and/or systemic effects of blue light retinal exposures.
Topics: Humans; Light; Vision, Ocular; Retina; Retinal Ganglion Cells; Visual Acuity
PubMed: 36983068
DOI: 10.3390/ijms24065998 -
Open Biology Apr 2023Individual retinal cell types exhibit semi-regular spatial patterns called retinal mosaics. Retinal ganglion cells (RGCs) and starburst amacrine cells (SACs) are known...
Individual retinal cell types exhibit semi-regular spatial patterns called retinal mosaics. Retinal ganglion cells (RGCs) and starburst amacrine cells (SACs) are known to exhibit such layouts. Mechanisms responsible for the formation of mosaics are not well understood but follow three main principles: (i) homotypic cells prevent nearby cells from adopting the same type, (ii) cell tangential migration and (iii) cell death. Alongside experiments in mouse, we use BioDynaMo, an agent-based simulation framework, to build a detailed and mechanistic model of mosaic formation. We investigate the implications of the three theories for RGC's mosaic formation. We report that the cell migration mechanism yields the most regular mosaics. In addition, we propose that low-density RGC type mosaics exhibit on average low regularities, and thus we question the relevance of regular spacing as a criterion for a group of RGCs to form a RGC type. We investigate SAC mosaics formation and interactions between the ganglion cell layer (GCL) and inner nuclear layer (INL) populations. We propose that homotypic interactions between the GCL and INL populations during mosaics creation are required to reproduce the observed SAC mosaics' characteristics. This suggests that the GCL and INL populations of SACs might not be independent during retinal development.
Topics: Mice; Animals; Retinal Ganglion Cells; Amacrine Cells; Retina; Software; Computer Simulation
PubMed: 37015288
DOI: 10.1098/rsob.220217 -
Trends in Neurosciences Jun 2022The center-surround receptive field of retinal ganglion cells represents a fundamental concept for how the retina processes and encodes visual information. Yet,... (Review)
Review
The center-surround receptive field of retinal ganglion cells represents a fundamental concept for how the retina processes and encodes visual information. Yet, traditional approaches of using the receptive field as a linear filter to integrate light intensity over space often do not capture the responses of a ganglion cell to complex visual stimuli. Thus, models with local nonlinearities in subunits of the receptive field or with local temporal dynamics are emerging to better reflect relevant aspects of retinal circuitry and capture stimulus encoding. Here, we review recent efforts to identify such receptive-field substructure and evaluate its role in visual stimulus encoding. The concomitant development of new computational tools may pave the way toward a model-based, functional approach to retinal circuit analysis.
Topics: Humans; Light; Photic Stimulation; Retina; Retinal Ganglion Cells
PubMed: 35422357
DOI: 10.1016/j.tins.2022.03.005 -
Journal of Pediatric Ophthalmology and... Jul 2018
Review
Topics: Animals; Apoptosis; Autophagy; Eye Proteins; Humans; Retinal Degeneration; Retinal Ganglion Cells
PubMed: 30024017
DOI: 10.3928/01913913-20180530-01 -
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 -
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 -
Cells Jun 2021As in glaucoma and other optic neuropathies cellular dysfunction often precedes cell death, the assessment of retinal ganglion cell (RGC) function represents a key... (Review)
Review
As in glaucoma and other optic neuropathies cellular dysfunction often precedes cell death, the assessment of retinal ganglion cell (RGC) function represents a key outcome measure for neuroprotective strategies aimed at targeting distressed but still viable cells. RGC dysfunction can be assessed with the pattern electroretinogram (PERG), a sensitive measure of electrical activity of RGCs that is recorded non-invasively in human subjects and mouse models. Here, we offer a conceptual framework based on an intuitive state-transition model used for disease management in patients to identify progressive, potentially reversible stages of RGC dysfunction leading to cell death in mouse models of glaucoma and other optic neuropathies. We provide mathematical equations to describe state-transitions with a set of modifiable parameters that alter the time course and severity of state-transitions, which can be used for hypothesis testing and fitting experimental PERG data. PERG dynamics as a function of physiological stimuli are also used to differentiate phenotypic and altered RGC response dynamics, to assess susceptibility to stressors and to assess reversible dysfunction upon pharmacological treatment.
Topics: Animals; Disease Models, Animal; Electroretinography; Humans; Mice; Models, Neurological; Optic Nerve Diseases; Retinal Ganglion Cells
PubMed: 34198840
DOI: 10.3390/cells10061398 -
The Molecular Mechanisms Involved in Axonal Degeneration and Retrograde Retinal Ganglion Cell Death.DNA and Cell Biology Nov 2023Axonal degeneration is a pathologic change common to multiple retinopathies and optic neuropathies. Various pathologic factors, such as mechanical injury, inflammation,... (Review)
Review
Axonal degeneration is a pathologic change common to multiple retinopathies and optic neuropathies. Various pathologic factors, such as mechanical injury, inflammation, and ischemia, can damage retinal ganglion cell (RGC) somas and axons, eventually triggering axonal degeneration and RGC death. The molecular mechanisms of somal and axonal degeneration are distinct but also overlap, and axonal degeneration can result in retrograde somal degeneration. While the mitogen-activated protein kinase pathway acts as a central node in RGC axon degeneration, several newly discovered molecules, such as sterile alpha and Toll/interleukin-1 receptor motif-containing protein 1 and nicotinamide mononucleotide adenylyltransferase 2, also play a critical role in this pathological process following different types of injury. Therefore, we summarize the types of injury that cause RGC axon degeneration and retrograde RGC death and important underlying molecular mechanisms, providing a reference for the identification of targets for protecting axons and RGCs.
Topics: Retinal Ganglion Cells; Axons
PubMed: 37819746
DOI: 10.1089/dna.2023.0180 -
International Journal of Molecular... Jul 2021Retinal ganglion cells (RGCs) are a population of neurons of the central nervous system (CNS) extending with their soma to the inner retina and with their axons to the... (Review)
Review
Retinal ganglion cells (RGCs) are a population of neurons of the central nervous system (CNS) extending with their soma to the inner retina and with their axons to the optic nerve. Glaucoma represents a group of neurodegenerative diseases where the slow progressive death of RGCs results in a permanent loss of vision. To date, although Intra Ocular Pressure (IOP) is considered the main therapeutic target, the precise mechanisms by which RGCs die in glaucoma have not yet been clarified. In fact, Primary Open Angle Glaucoma (POAG), which is the most common glaucoma form, also occurs without elevated IOP. This present review provides a summary of some pathological conditions, i.e., axonal transport blockade, glutamate excitotoxicity and changes in pro-inflammatory cytokines along the RGC projection, all involved in the glaucoma cascade. Moreover, neuro-protective therapeutic approaches, which aim to improve RGC degeneration, have also been taken into consideration.
Topics: Animals; Axonal Transport; Axons; Disease Models, Animal; Glaucoma; Humans; Neuroprotection; Optic Nerve; Retinal Ganglion Cells
PubMed: 34360760
DOI: 10.3390/ijms22157994 -
The New England Journal of Medicine May 2021
Topics: Aging; Animals; Cellular Reprogramming; Disease Models, Animal; Epigenesis, Genetic; Glaucoma; Mice; Nerve Regeneration; Octamer Transcription Factor-3; Optic Nerve Injuries; Retinal Ganglion Cells
PubMed: 33951368
DOI: 10.1056/NEJMcibr2034927