10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      The Retina of Osteopontin deficient Mice in Aging

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Osteopontin (OPN) is a secreted glycosylated phosphoprotein that influences cell survival, inflammation, migration, and homeostasis after injury. As the role of OPN in the retina remains unclear, this study issue was addressed by aiming to study how the absence of OPN in knock-out mice affects the retina and the influence of age on these effects. The study focused on retinal ganglion cells (RGCs) and glial cells (astrocytes, Müller cells, and resident microglia) in 3- and 20-month-old mice. The number of RGCs in the retina was quantified and the area occupied by astrocytes was measured. In addition, the morphology of Müller cells and microglia was examined in retinal sections. The deficiency in OPN reduces RGC density by 25.09% at 3 months of age and by 60.37% at 20 months of age. The astrocyte area was also reduced by 51.01% in 3-month-old mice and by 57.84% at 20 months of age, although Müller glia and microglia did not seem to be affected by the lack of OPN. This study demonstrates the influence of OPN on astrocytes and RGCs, whereby the absence of OPN in the retina diminishes the area occupied by astrocytes and produces a secondary reduction in the number of RGCs. Accordingly, OPN could be a target to develop therapies to combat neurodegenerative diseases and astrocytes may represent a key mediator of such effects.

          Related collections

          Most cited references56

          • Record: found
          • Abstract: found
          • Article: not found

          Retinal ischemia: mechanisms of damage and potential therapeutic strategies.

          Retinal ischemia is a common cause of visual impairment and blindness. At the cellular level, ischemic retinal injury consists of a self-reinforcing destructive cascade involving neuronal depolarisation, calcium influx and oxidative stress initiated by energy failure and increased glutamatergic stimulation. There is a cell-specific sensitivity to ischemic injury which may reflect variability in the balance of excitatory and inhibitory neurotransmitter receptors on a given cell. A number of animal models and analytical techniques have been used to study retinal ischemia, and an increasing number of treatments have been shown to interrupt the "ischemic cascade" and attenuate the detrimental effects of retinal ischemia. Thus far, however, success in the laboratory has not been translated to the clinic. Difficulties with the route of administration, dosage, and adverse effects may render certain experimental treatments clinically unusable. Furthermore, neuroprotection-based treatment strategies for stroke have so far been disappointing. However, compared to the brain, the retina exhibits a remarkable natural resistance to ischemic injury, which may reflect its peculiar metabolism and unique environment. Given the increasing understanding of the events involved in ischemic neuronal injury it is hoped that clinically effective treatments for retinal ischemia will soon be available.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Osteopontin: role in immune regulation and stress responses.

            Recent research has led to a better but as yet incomplete understanding of the complex roles osteopontin plays in mammalian physiology. A soluble protein found in all body fluids, it stimulates signal transduction pathways (via integrins and CD44 variants) similar to those stimulated by components of the extracellular matrix. This appears to promote the survival of cells exposed to potentially lethal insults such as ischemia/reperfusion or physical/chemical trauma. OPN is chemotactic for many cell types including macrophages, dendritic cells, and T cells; it enhances B lymphocyte immunoglobulin production and proliferation. In inflammatory situations it stimulates both pro- and anti-inflammatory processes, which on balance can be either beneficial or harmful depending on what other inputs the cell is receiving. OPN influences cell-mediated immunity and has been shown to have Th1-cytokine functions. OPN deficiency is linked to a reduced Th1 immune response in infectious diseases, autoimmunity and delayed type hypersensitivity. OPN's role in the central nervous system and in stress responses has also emerged as an important aspect related to its cytoprotective and immune functions. Evidence suggests that either OPN or anti-OPN monoclonal antibodies (depending on the circumstances) might be clinically useful in modulating OPN function. Manipulation of plasma OPN levels may be useful in the treatment of autoimmune disease, cancer metastasis, osteoporosis and some forms of stress.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Retinal microglia: just bystander or target for therapy?

              Resident microglial cells can be regarded as the immunological watchdogs of the brain and the retina. They are active sensors of their neuronal microenvironment and rapidly respond to various insults with a morphological and functional transformation into reactive phagocytes. There is strong evidence from animal models and in situ analyses of human tissue that microglial reactivity is a common hallmark of various retinal degenerative and inflammatory diseases. These include rare hereditary retinopathies such as retinitis pigmentosa and X-linked juvenile retinoschisis but also comprise more common multifactorial retinal diseases such as age-related macular degeneration, diabetic retinopathy, glaucoma, and uveitis as well as neurological disorders with ocular manifestation. In this review, we describe how microglial function is kept in balance under normal conditions by cross-talk with other retinal cells and summarize how microglia respond to different forms of retinal injury. In addition, we present the concept that microglia play a key role in local regulation of complement in the retina and specify aspects of microglial aging relevant for chronic inflammatory processes in the retina. We conclude that this resident immune cell of the retina cannot be simply regarded as bystander of disease but may instead be a potential therapeutic target to be modulated in the treatment of degenerative and inflammatory diseases of the retina.
                Bookmark

                Author and article information

                Contributors
                http://www.ehu.es/GOBE
                http://www.ehu.es/GOBE
                (34) 94 6012820 , elena.vecino@ehu.es , http://www.ehu.es/GOBE
                Journal
                Mol Neurobiol
                Mol. Neurobiol
                Molecular Neurobiology
                Springer US (New York )
                0893-7648
                1559-1182
                2 September 2017
                2 September 2017
                2018
                : 55
                : 1
                : 213-221
                Affiliations
                [1 ]ISNI 0000000121671098, GRID grid.11480.3c, Department of Cell Biology and Histology, , University of Basque Country, www.ehu.es/GOBE, Experimental Ophtalmo-Biology Group UPV/EHU, ; Vizcaya, Spain
                [2 ]Biocruces Research Institute, Barakaldo, Spain
                [3 ]ISNI 0000000121671098, GRID grid.11480.3c, Department of Physiology, , University of the Basque Country UPV/EHU, ; Vizcaya, Spain
                [4 ]ISNI 0000000121671098, GRID grid.11480.3c, Department of Ophthalmology, , University of the Basque Country UPV/EHU, ; Vizcaya, Spain
                Article
                734
                10.1007/s12035-017-0734-9
                5808060
                28866734
                ce98780f-a964-4410-aaad-063089e1fabb
                © The Author(s) 2017

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                Categories
                Article
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2018

                Neurosciences
                retina,osteopontin,retinal ganglion cells,glia,astrocytes,müller cells,microglia
                Neurosciences
                retina, osteopontin, retinal ganglion cells, glia, astrocytes, müller cells, microglia

                Comments

                Comment on this article