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Molecular Aspects of Medicine Dec 2023Glaucoma is a complex multifactorial eye disease manifesting in retinal ganglion cell (RGC) death and optic nerve degeneration, ultimately causing irreversible vision... (Review)
Review
Glaucoma is a complex multifactorial eye disease manifesting in retinal ganglion cell (RGC) death and optic nerve degeneration, ultimately causing irreversible vision loss. Research in recent years has significantly enhanced our understanding of RGC degenerative mechanisms in glaucoma. It is evident that high intraocular pressure (IOP) is not the only contributing factor to glaucoma pathogenesis. The equilibrium of pro-survival and pro-death signalling pathways in the retina strongly influences the function and survival of RGCs and optic nerve axons in glaucoma. Molecular evidence from human retinal tissue analysis and a range of experimental models of glaucoma have significantly contributed to unravelling these mechanisms. Accumulating evidence reveals a wide range of molecular signalling pathways that can operate -either alone or via intricate networks - to induce neurodegeneration. The roles of several molecules, including neurotrophins, interplay of intracellular kinases and phosphates, caveolae and adapter proteins, serine proteases and their inhibitors, nuclear receptors, amyloid beta and tau, and how their dysfunction affects retinal neurons are discussed in this review. We further underscore how anatomical alterations in various animal models exhibiting RGC degeneration and susceptibility to glaucoma-related neuronal damage have helped to characterise molecular mechanisms in glaucoma. In addition, we also present different regulated cell death pathways that play a critical role in RGC degeneration in glaucoma.
Topics: Animals; Humans; Amyloid beta-Peptides; Glaucoma; Retina; Retinal Ganglion Cells; Cell Death; Disease Models, Animal
PubMed: 37856930
DOI: 10.1016/j.mam.2023.101216 -
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 -
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 -
Romanian Journal of Ophthalmology 2023Retinal neuronal and vascular changes have been observed in multiple sclerosis (MS) patients. The aim of this review was to highlight the most current optical coherence... (Review)
Review
Retinal neuronal and vascular changes have been observed in multiple sclerosis (MS) patients. The aim of this review was to highlight the most current optical coherence tomography (OCT) and optical coherence tomography angiography (OCT-A) data in MS and to provide information about the possibility of using OCT / OCT-A parameters as biomarkers for screening, diagnosis and monitoring of MS. To carry out this review, a meticulous literature search was undergone on PubMed between 2014 and the present day, using the following terms: "multiple", "sclerosis", "optical", "coherence", "tomography" and "angiography". Additional studies were found via references, being chosen according to relevance. Retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) were significantly lower in MS patients compared to controls, and correlated with clinical and paraclinical variables, such as visual function, disability, and magnetic resonance imaging (MRI). Retinal capillary plexuses could be higher, lower or the same, and the best OCT-A microvasculature parameter for the detection of MS was the superficial capillary plexus (SCP). The reduced retinal vessel density (VD) was correlated with the disability in MS. OCT and OCT-A parameters could improve the development of retinal biomarkers for screening, early diagnosis and monitoring the disease progression of MS, and they could improve the development of potential future therapies that could slow or stop the course of this incurable disease. DCP = deep capillary plexus; EDSS = Expanded Disability Status Scale; GCC = ganglion cell complex; GCL = ganglion cell layer; MRI = magnetic resonance imaging; MS = Multiple sclerosis; OCT = optical coherence tomography; OCT-A = optical coherence tomography angiography; ON = optic neuritis; RNFL = retinal nerve fiber layer; SCP = superficial capillary plexus; VD = vessel density.
Topics: Humans; Multiple Sclerosis; Tomography, Optical Coherence; Retinal Ganglion Cells; Nerve Fibers; Biomarkers
PubMed: 37522023
DOI: 10.22336/rjo.2023.20 -
Eye (London, England) Sep 2021Clinical electrophysiological assessment of optic nerve and retinal ganglion cell function can be performed using the Pattern Electroretinogram (PERG), Visual Evoked... (Review)
Review
Clinical electrophysiological assessment of optic nerve and retinal ganglion cell function can be performed using the Pattern Electroretinogram (PERG), Visual Evoked Potential (VEP) and the Photopic Negative Response (PhNR) amongst other more specialised techniques. In this review, we describe these electrophysiological techniques and their application in diseases affecting the optic nerve and retinal ganglion cells with the exception of glaucoma. The disease groups discussed include hereditary, compressive, toxic/nutritional, traumatic, vascular, inflammatory and intracranial causes for optic nerve or retinal ganglion cell dysfunction. The benefits of objective, electrophysiological measurement of the retinal ganglion cells and optic nerve are discussed, as are their applications in clinical diagnosis of disease, determining prognosis, monitoring progression and response to novel therapies.
Topics: Electroretinography; Evoked Potentials, Visual; Glaucoma; Humans; Optic Nerve; Retinal Ganglion Cells
PubMed: 34117382
DOI: 10.1038/s41433-021-01614-x -
International Journal of Molecular... Feb 2024Glaucoma is a progressive neurodegenerative disease characterized by damage to the optic nerve that results in irreversible vision loss. While the exact pathology of... (Review)
Review
Glaucoma is a progressive neurodegenerative disease characterized by damage to the optic nerve that results in irreversible vision loss. While the exact pathology of glaucoma is not well understood, emerging evidence suggests that dysregulation of the complement system, a key component of innate immunity, plays a crucial role. In glaucoma, dysregulation of the complement cascade and impaired regulation of complement factors contribute to chronic inflammation and neurodegeneration. Complement components such as C1Q, C3, and the membrane attack complex have been implicated in glaucomatous neuroinflammation and retinal ganglion cell death. This review will provide a summary of human and experimental studies that document the dysregulation of the complement system observed in glaucoma patients and animal models of glaucoma driving chronic inflammation and neurodegeneration. Understanding how complement-mediated damage contributes to glaucoma will provide opportunities for new therapies.
Topics: Animals; Humans; Neurodegenerative Diseases; Glaucoma; Retinal Ganglion Cells; Complement System Proteins; Inflammation; Disease Models, Animal
PubMed: 38396986
DOI: 10.3390/ijms25042307 -
International Journal of Molecular... Apr 2021Glaucoma, the second leading cause of blindness worldwide, is an incurable neurodegenerative disorder due to the dysfunction of retinal ganglion cells (RGCs). RGCs... (Review)
Review
Glaucoma, the second leading cause of blindness worldwide, is an incurable neurodegenerative disorder due to the dysfunction of retinal ganglion cells (RGCs). RGCs function as the only output neurons conveying the detected light information from the retina to the brain, which is a bottleneck of vision formation. RGCs in mammals cannot regenerate if injured, and RGC subtypes differ dramatically in their ability to survive and regenerate after injury. Recently, novel RGC subtypes and markers have been uncovered in succession. Meanwhile, apart from great advances in RGC axon regeneration, some degree of experimental RGC regeneration has been achieved by the in vitro differentiation of embryonic stem cells and induced pluripotent stem cells or in vivo somatic cell reprogramming, which provides insights into the future therapy of myriad neurodegenerative disorders. Further approaches to the combination of different factors will be necessary to develop efficacious future therapeutic strategies to promote ultimate axon and RGC regeneration and functional vision recovery following injury.
Topics: Animals; Axons; Cell Differentiation; Embryonic Stem Cells; Humans; Induced Pluripotent Stem Cells; Nerve Regeneration; Optic Nerve; Retinal Ganglion Cells
PubMed: 33924833
DOI: 10.3390/ijms22094616 -
Cellular and Molecular Life Sciences :... Feb 2021The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) are a relatively recently discovered class of atypical ganglion cell... (Review)
Review
The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) are a relatively recently discovered class of atypical ganglion cell photoreceptor. These ipRGCs are a morphologically and physiologically heterogeneous population that project widely throughout the brain and mediate a wide array of visual functions ranging from photoentrainment of our circadian rhythms, to driving the pupillary light reflex to improve visual function, to modulating our mood, alertness, learning, sleep/wakefulness, regulation of body temperature, and even our visual perception. The presence of melanopsin as a unique molecular signature of ipRGCs has allowed for the development of a vast array of molecular and genetic tools to study ipRGC circuits. Given the emerging complexity of this system, this review will provide an overview of the genetic tools and methods used to study ipRGCs, how these tools have been used to dissect their role in a variety of visual circuits and behaviors in mice, and identify important directions for future study.
Topics: Animals; Animals, Genetically Modified; Phosphoric Diester Hydrolases; Retina; Retinal Ganglion Cells; Rod Opsins; TRPC Cation Channels; Transcription Factor Brn-3B; Type C Phospholipases; Visual Pathways
PubMed: 32965515
DOI: 10.1007/s00018-020-03641-5 -
International Journal of Molecular... Apr 2022The retina is part of the central nervous system, its analysis may provide an idea of the health and functionality, not only of the retina, but also of the entire... (Review)
Review
The retina is part of the central nervous system, its analysis may provide an idea of the health and functionality, not only of the retina, but also of the entire central nervous system, as has been shown in Alzheimer's or Parkinson's diseases. Within the retina, the ganglion cells (RGC) are the neurons in charge of processing and sending light information to higher brain centers. Diverse insults and pathological states cause degeneration of RGC, leading to irreversible blindness or impaired vision. RGCs are the measurable endpoints in current research into experimental therapies and diagnosis in multiple ocular pathologies, like glaucoma. RGC subtype classifications are based on morphological, functional, genetical, and immunohistochemical aspects. Although great efforts are being made, there is still no classification accepted by consensus. Moreover, it has been observed that each RGC subtype has a different susceptibility to injury. Characterizing these subtypes together with cell death pathway identification will help to understand the degenerative process in the different injury and pathological models, and therefore prevent it. Here we review the known RGC subtypes, as well as the diagnostic techniques, probes, and biomarkers for programmed and unprogrammed cell death in RGC.
Topics: Animals; Biomarkers; Disease Models, Animal; Glaucoma; Humans; Retina; Retinal Degeneration; Retinal Ganglion Cells; Vision, Ocular
PubMed: 35457104
DOI: 10.3390/ijms23084287 -
The Journal of Comparative Neurology Apr 2022Recent advances in single-cell RNA sequencing have enabled the molecular distinction of ganglion cell populations in mammalian retinas. Here we used antibodies against...
Recent advances in single-cell RNA sequencing have enabled the molecular distinction of ganglion cell populations in mammalian retinas. Here we used antibodies against the transcription factor special AT-rich binding protein 1 (Satb1, a protein which is expressed by on-off direction-selective ganglion cells in mouse retina) to study Satb1 expression in the retina of marmosets (Callithrix jacchus), macaques (Macaca fascicularis), and humans. In all species, Satb1 was exclusively expressed in retinal ganglion cells. The Satb1 cells made up ∼2% of the ganglion cell population in the central retina of all species, rising to a maximum ∼7% in peripheral marmoset retina. Intracellular injections in marmoset and macaque retinas revealed that most Satb1 expressing ganglion cells are widefield ganglion cells. In marmoset, Satb1 cells have a densely branching dendritic tree and include broad and narrow thorny, recursive bistratified, and parasol cells, all of which show some costratification with the outer or inner cholinergic amacrine cells. The recursive bistratified cells showed the strongest costratification but did not show extensive cofasciculation as reported for on-off direction-selective ganglion cells in rabbit and rodent retinas. In macaque, Satb1 was not expressed in recursive bistratified cells, but in large sparsely branching cells. Our findings further support the idea that the expression of transcription factors in retinal ganglion cells is not conserved across Old World (human and macaque) and New World (marmoset) primates and provides a further step to link a molecular marker with specific cell types.
Topics: Animals; Callithrix; Humans; Macaca fascicularis; Matrix Attachment Region Binding Proteins; Retinal Ganglion Cells; Species Specificity
PubMed: 34622958
DOI: 10.1002/cne.25258