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      The Susceptibility of Retinal Ganglion Cells to Optic Nerve Injury is Type Specific

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          Abstract

          Retinal ganglion cell (RGC) death occurs in many eye diseases, such as glaucoma and traumatic optic neuropathy (TON). Increasing evidence suggests that the susceptibility of RGCs varies to different diseases in an RGC type-dependent manner. We previously showed that the susceptibility of several genetically identified RGC types to N-methyl-D-aspartate (NMDA) excitotoxicity differs significantly. In this study, we characterize the susceptibility of the same RGC types to optic nerve crush (ONC). We show that the susceptibility of these RGC types to ONC varies significantly, in which BD-RGCs are the most resistant RGC type while W3-RGCs are the most sensitive cells to ONC. We also show that the survival rates of BD-RGCs and J-RGCs after ONC are significantly higher than their survival rates after NMDA excitotoxicity. These results are consistent with the conclusion that the susceptibility of RGCs to ONC varies in an RGC type-dependent manner. Further, the susceptibilities of the same types of RGCs to ONC and NMDA excitotoxicity are significantly different. These are valuable insights for understanding of the selective susceptibility of RGCs to various pathological insults and the development of a strategy to protect RGCs from death in disease conditions.

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          Most cited references78

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          The types of retinal ganglion cells: current status and implications for neuronal classification.

          In the retina, photoreceptors pass visual information to interneurons, which process it and pass it to retinal ganglion cells (RGCs). Axons of RGCs then travel through the optic nerve, telling the rest of the brain all it will ever know about the visual world. Research over the past several decades has made clear that most RGCs are not merely light detectors, but rather feature detectors, which send a diverse set of parallel, highly processed images of the world on to higher centers. Here, we review progress in classification of RGCs by physiological, morphological, and molecular criteria, making a particular effort to distinguish those cell types that are definitive from those for which information is partial. We focus on the mouse, in which molecular and genetic methods are most advanced. We argue that there are around 30 RGC types and that we can now account for well over half of all RGCs. We also use RGCs to examine the general problem of neuronal classification, arguing that insights and methods from the retina can guide the classification enterprise in other brain regions.
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            Subtype-specific regeneration of retinal ganglion cells following axotomy: effects of osteopontin and mTOR signaling.

            In mammals, few retinal ganglion cells (RGCs) survive following axotomy, and even fewer regenerate axons. This could reflect differential extrinsic influences or the existence of subpopulations that vary in their responses to injury. We tested these alternatives by comparing responses of molecularly distinct subsets of mouse RGCs to axotomy. Survival rates varied dramatically among subtypes, with alpha-RGCs (αRGCs) surviving preferentially. Among survivors, αRGCs accounted for nearly all regeneration following downregulation of PTEN, which activates the mTOR pathway. αRGCs have uniquely high mTOR signaling levels among RGCs and also selectively express osteopontin (OPN) and receptors for the insulin-like growth factor 1 (IGF-1). Administration of OPN plus IGF-1 promotes regeneration as effectively as downregulation of PTEN; however, regeneration is still confined to αRGCs. Our results reveal dramatic subtype-specific differences in the ability of RGCs to survive and regenerate following injury, and they identify promising agents for promoting axonal regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.
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              Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis.

              Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Due to its high prevalence, MS is the leading cause of non-traumatic neurological disability in young adults in the United States and Europe. The clinical disease course is variable and starts with reversible episodes of neurological disability in the third or fourth decade of life. This transforms into a disease of continuous and irreversible neurological decline by the sixth or seventh decade. Available therapies for MS patients have little benefit for patients who enter this irreversible phase of the disease. It is well established that irreversible loss of axons and neurons are the major cause of the irreversible and progressive neurological decline that most MS patients endure. This review discusses the etiology, mechanisms and progress made in determining the cause of axonal and neuronal loss in MS. Copyright © 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Cells
                Cells
                cells
                Cells
                MDPI
                2073-4409
                10 March 2020
                March 2020
                : 9
                : 3
                : 677
                Affiliations
                [1 ]VA Salt Lake City Health Care System, Salt Lake City, UT 84148, USA; yangning0903@ 123456hotmail.com (N.Y.); brent.k.young@ 123456utah.edu (B.K.Y.); ping.wang@ 123456utah.edu (P.W.)
                [2 ]Ophthalmology and Visual Sciences, University of Utah, Salt Lake City, UT 84132, USA
                [3 ]Interdepartmental Neuroscience Program, University of Utah, Salt Lake City, UT 84114, USA
                Author notes
                [* ]Correspondence: ning.tian@ 123456hsc.utah.edu ; Tel.: +01-801-213-2852
                Author information
                https://orcid.org/0000-0003-3036-0202
                https://orcid.org/0000-0003-0491-278X
                Article
                cells-09-00677
                10.3390/cells9030677
                7140711
                32164319
                80d90280-27b4-4b3d-9482-10e345bd1d3e
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 03 February 2020
                : 09 March 2020
                Categories
                Article

                retinal ganglion cell death,optic nerve crush,nmda excitotoxicity,rgc type-specific susceptibility

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