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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 -
Cellular and Molecular Life Sciences :... May 2021Retinal ganglion cells (RGCs) are the only projection neurons in the neural retina. They receive and integrate visual signals from upstream retinal neurons in the visual... (Review)
Review
Retinal ganglion cells (RGCs) are the only projection neurons in the neural retina. They receive and integrate visual signals from upstream retinal neurons in the visual circuitry and transmit them to the brain. The function of RGCs is performed by the approximately 40 RGC types projecting to various central brain targets. RGCs are the first cell type to form during retinogenesis. The specification and differentiation of the RGC lineage is a stepwise process; a hierarchical gene regulatory network controlling the RGC lineage has been identified and continues to be elaborated. Recent studies with single-cell transcriptomics have led to unprecedented new insights into their types and developmental trajectory. In this review, we summarize our current understanding of the functions and relationships of the many regulators of the specification and differentiation of the RGC lineage. We emphasize the roles of these key transcription factors and pathways in different developmental steps, including the transition from retinal progenitor cells (RPCs) to RGCs, RGC differentiation, generation of diverse RGC types, and central projection of the RGC axons. We discuss critical issues that remain to be addressed for a comprehensive understanding of these different aspects of RGC genesis and emerging technologies, including single-cell techniques, novel genetic tools and resources, and high-throughput genome editing and screening assays, which can be leveraged in future studies.
Topics: Animals; Cell Differentiation; Cell Lineage; Gene Expression Regulation; Humans; Retina; Retinal Ganglion Cells; Signal Transduction; Stem Cells; Transcription Factors
PubMed: 33782712
DOI: 10.1007/s00018-021-03814-w -
Current Opinion in Ophthalmology Mar 2015The present review describes new advances in our understanding of the role of glial cells in the pathogenesis of glaucoma. It is becoming clear that retinal glia should... (Review)
Review
PURPOSE OF REVIEW
The present review describes new advances in our understanding of the role of glial cells in the pathogenesis of glaucoma. It is becoming clear that retinal glia should not be studied in isolation in glaucoma because glia have dynamic and diverse interactions with a range of different cell types that could influence the disease process.
RECENT FINDINGS
Microglial activity is modulated by signals from retinal ganglion cells and macroglia that influence RGC survival in various models of injury. New studies suggest that circulating monocytic populations may play a role in mediating the immune response to glaucoma. Astrocytes have been found to develop discrete localized processes that interact with a specific subset of retinal ganglion cells, possibly responding to the expression of phagocytic signals by stressed retinal ganglion cells.
SUMMARY
Retinal glia constitute a highly versatile population that interacts with various cells to maintain homeostasis and limit disease. Defining the mechanisms that underlie glial communication could enable the development of more selective therapeutic targets, with great potential clinical applications.
Topics: Animals; Cell Communication; Glaucoma; Humans; Macrophages; Neuroglia; Retinal Ganglion Cells
PubMed: 25490529
DOI: 10.1097/ICU.0000000000000125 -
Seminars in Cell & Developmental Biology Jan 2019In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal... (Review)
Review
In order to navigate through the surrounding environment many mammals, including humans, primarily rely on vision. The eye, composed of the choroid, sclera, retinal pigmented epithelium, cornea, lens, iris and retina, is the structure that receives the light and converts it into electrical impulses. The retina contains six major types of neurons involving in receiving and modifying visual information and passing it onto higher visual processing centres in the brain. Visual information is relayed to the brain via the axons of retinal ganglion cells (RGCs), a projection known as the optic pathway. The proper formation of this pathway during development is essential for normal vision in the adult individual. Along this pathway there are several points where visual axons face 'choices' in their direction of growth. Understanding how these choices are made has advanced significantly our knowledge of axon guidance mechanisms. Thus, the development of the visual pathway has served as an extremely useful model to reveal general principles of axon pathfinding throughout the nervous system. However, due to its particularities, some cellular and molecular mechanisms are specific for the visual circuit. Here we review both general and specific mechanisms involved in the guidance of mammalian RGC axons when they are traveling from the retina to the brain to establish precise and stereotyped connections that will sustain vision.
Topics: Animals; Axon Guidance; Axons; Humans; Retinal Ganglion Cells
PubMed: 29174916
DOI: 10.1016/j.semcdb.2017.11.027 -
Tissue Engineering. Part B, Reviews Oct 2019Glaucoma is a major eye disease characterized by a progressive loss of retinal ganglion cells (RGCs). Biomechanical forces as a result of hydrostatic pressure and strain... (Review)
Review
Glaucoma is a major eye disease characterized by a progressive loss of retinal ganglion cells (RGCs). Biomechanical forces as a result of hydrostatic pressure and strain play a role in this disease. Decreasing intraocular pressure is the only available therapy so far, but is not always effective and does not prevent blindness in many cases. There is a need for drugs that protect RGCs from dying in glaucoma; to develop these, we need valid glaucoma and drug screening models. Since models are unsuitable for screening purposes, we focus on and models in this review. Many groups have studied pressure and strain model systems to mimic glaucoma, to investigate the molecular and cellular events leading to mechanically induced RGC death. Therefore, the focus of this review is on the different mechanical model systems used to mimic the biomechanical forces in glaucoma. Most models use either cell or tissue strain, or fluid- or gas-controlled hydrostatic pressure application and apply it to the relevant cell types such as trabecular meshwork cells, optic nerve head astrocytes, and RGCs, but also to entire eyes. New model systems are warranted to study concepts and test experimental compounds for the development of new drugs to protect vision in glaucoma patients. Impact Statement The outcome of currently developed models to investigate mechanically induced retinal ganglion cell death by applying different mechanical strains varies widely. This suggests that a robust glaucoma model has not been developed yet. However, a comprehensive overview of current developments is not available. In this review, we have therefore assessed what has been done before and summarized the available knowledge in the field, which can be used to develop improved models for glaucoma research.
Topics: Animals; Disease Models, Animal; Drug Evaluation, Preclinical; Glaucoma; Humans; Intraocular Pressure; Neuroprotective Agents; Retinal Ganglion Cells
PubMed: 31088331
DOI: 10.1089/ten.TEB.2019.0044 -
International Journal of Molecular... Jun 2019Melanopsin-containing retinal ganglion cells (mRGCs) represent a third class of retinal photoreceptors involved in regulating the pupillary light reflex and circadian... (Review)
Review
Melanopsin-containing retinal ganglion cells (mRGCs) represent a third class of retinal photoreceptors involved in regulating the pupillary light reflex and circadian photoentrainment, among other things. The functional integrity of the circadian system and melanopsin cells is an essential component of well-being and health, being both impaired in aging and disease. Here we review evidence of melanopsin-expressing cell alterations in aging and neurodegenerative diseases and their correlation with the development of circadian rhythm disorders. In healthy humans, the average density of melanopsin-positive cells falls after age 70, accompanied by age-dependent atrophy of dendritic arborization. In addition to aging, inner and outer retinal diseases also involve progressive deterioration and loss of mRGCs that positively correlates with progressive alterations in circadian rhythms. Among others, mRGC number and plexus complexity are impaired in Parkinson's disease patients; changes that may explain sleep and circadian rhythm disorders in this pathology. The key role of mRGCs in circadian photoentrainment and their loss in age and disease endorse the importance of eye care, even if vision is lost, to preserve melanopsin ganglion cells and their essential functions in the maintenance of an adequate quality of life.
Topics: Aging; Animals; Circadian Rhythm; Humans; Neurodegenerative Diseases; Retinal Ganglion Cells; Rod Opsins
PubMed: 31261700
DOI: 10.3390/ijms20133164 -
International Journal of Molecular... Mar 2020Diabetes produces several changes in the body triggered by high glycemia. Some of these changes include altered metabolism, structural changes in blood vessels and... (Review)
Review
Diabetes produces several changes in the body triggered by high glycemia. Some of these changes include altered metabolism, structural changes in blood vessels and chronic inflammation. The eye and particularly the retinal ganglion cells (RGCs) are not spared, and the changes eventually lead to cell loss and visual function impairment. Understanding the mechanisms resulting in RGC damage and loss from diabetic retinopathy is essential to find an effective treatment. This review focuses mainly on the signaling pathways and molecules involved in RGC loss and the potential therapeutic approaches for the prevention of this cell death. Throughout the manuscript it became evident that multiple factors of different kind are responsible for RGC damage. This shows that new therapeutic agents targeting several factors at the same time are needed. Alpha-1 antitrypsin as an anti-inflammatory agent may become a suitable option for the treatment of RGC loss because of its beneficial interaction with several signaling pathways involved in RGC injury and inflammation. In conclusion, alpha-1 antitrypsin may become a potential therapeutic agent for the treatment of RGC loss and processes behind diabetic retinopathy.
Topics: Animals; Cell Death; Diabetes Mellitus; Diabetic Retinopathy; Humans; Inflammation; Molecular Targeted Therapy; Retinal Ganglion Cells; Signal Transduction
PubMed: 32231131
DOI: 10.3390/ijms21072351 -
Eye (London, England) Feb 2017Accumulating evidence from experimental and clinical studies suggest that retinal ganglion cells at least in the earlier stages of glaucoma have the capacity to recover... (Review)
Review
Accumulating evidence from experimental and clinical studies suggest that retinal ganglion cells at least in the earlier stages of glaucoma have the capacity to recover function following periods of functional loss. The capacity for recovery may be negatively impacted by advancing age but can be boosted by interventions such as diet restriction and exercise.
Topics: Aging; Animals; Diet; Disease Models, Animal; Exercise; Glaucoma; Humans; Recovery of Function; Retinal Ganglion Cells
PubMed: 28060359
DOI: 10.1038/eye.2016.281 -
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 -
Methods in Molecular Biology (Clifton,... 2023The identification of distinct retinal ganglion cell (RGC) populations in flat-mounted retinas is key to investigating pathological or pharmacological effects in these... (Review)
Review
The identification of distinct retinal ganglion cell (RGC) populations in flat-mounted retinas is key to investigating pathological or pharmacological effects in these cells. In this chapter, we review the main techniques for detecting the total population of RGCs and various of their subtypes in whole-mounted retinas of pigmented and albino rats and mice, four of the animal strains most studied by the scientific community in the retina field. These methods are based on the studies published by the Vidal-Sanz's laboratory.
Topics: Rats; Mice; Animals; Retinal Ganglion Cells; Retina
PubMed: 37558971
DOI: 10.1007/978-1-0716-3409-7_18