52
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Astrocytes in the optic nerve head express putative mechanosensitive channels

      research-article
      , ,
      Molecular Vision
      Molecular Vision

      Read this article at

      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

          Purpose

          To establish whether optic nerve head astrocytes express candidate molecules to sense tissue stretch.

          Methods

          We used conventional PCR, quantitative PCR, and single-cell reverse transcription PCR (RT–PCR) to assess the expression of various members of the transient receptor potential (TRP) channel family and of the recently characterized mechanosensitive channels Piezo1 and 2 in optic nerve head tissue and in single, isolated astrocytes.

          Results

          Most TRP subfamilies (TRPC, TRPM, TRPV, TRPA, and TRPP) and Piezo1 and 2 were expressed in the optic nerve head of the mouse. Quantitative real-time PCR analysis showed that TRPC1, TRPM7, TRPV2, TRPP2, and Piezo1 are the dominant isoforms in each subfamily. Single-cell RT–PCR revealed that many TRP isoforms, TRPC1–2, TRPC6, TRPV2, TRPV4, TRPM2, TRPM4, TRPM6–7, TRPP1–2, and Piezo1–2, are expressed in astrocytes of the optic nerve head, and that most astrocytes express TRPC1 and TRPP1–2. Comparisons of the TRPP and Piezo expression levels between different tissue regions showed that Piezo2 expression was higher in the optic nerve head and the optic nerve proper than in the brain and the corpus callosum. TRPP2 also showed higher expression in the optic nerve head.

          Conclusions

          Astrocytes in the optic nerve head express multiple putative mechanosensitive channels, in particular the recently identified channels Piezo1 and 2. The expression of putative mechanosensitive channels in these cells may contribute to their responsiveness to traumatic or glaucomatous injury.

          Related collections

          Most cited references92

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

          Piezos are pore-forming subunits of mechanically activated channels

          Mechanotransduction plays a crucial role in physiology. Biological processes including sensing touch and sound waves require yet unidentified cation channels that detect pressure. Mouse piezo1 (mpiezo1) and mpiezo2 induce mechanically activated cationic currents in cells; however, it is unknown if piezos are pore-forming ion channels or modulate ion channels. We show that Drosophila piezo (dpiezo) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. mpiezo1 assembles as a ~1.2 million-Dalton tetramer, with no evidence of other proteins in this complex. Finally, purified mpiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium red-sensitive ion channels. These data demonstrate that piezos are an evolutionarily conserved ion channel family involved in mechanotransduction.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Piezo1, a mechanically activated ion channel, is required for vascular development in mice.

            Mechanosensation is perhaps the last sensory modality not understood at the molecular level. Ion channels that sense mechanical force are postulated to play critical roles in a variety of biological processes including sensing touch/pain (somatosensation), sound (hearing), and shear stress (cardiovascular physiology); however, the identity of these ion channels has remained elusive. We previously identified Piezo1 and Piezo2 as mechanically activated cation channels that are expressed in many mechanosensitive cell types. Here, we show that Piezo1 is expressed in endothelial cells of developing blood vessels in mice. Piezo1-deficient embryos die at midgestation with defects in vascular remodeling, a process critically influenced by blood flow. We demonstrate that Piezo1 is activated by shear stress, the major type of mechanical force experienced by endothelial cells in response to blood flow. Furthermore, loss of Piezo1 in endothelial cells leads to deficits in stress fiber and cellular orientation in response to shear stress, linking Piezo1 mechanotransduction to regulation of cell morphology. These findings highlight an essential role of mammalian Piezo1 in vascular development during embryonic development.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Optic nerve damage in human glaucoma. II. The site of injury and susceptibility to damage.

              We examined the histologic structure of the optic nerve head in 15 eyes of nine persons with a known glaucoma history. All had been seeing eyes, varying from normal visual acuity and visual field to advanced glaucoma damage. The site of damage to nerve fibers is the scleral lamina cribrosa, where there is local blockage of axonal transport. Early cup size increase prior to definite field loss results from loss of nerve fibers, not from damage to astrocytic glial cells of the nerve head. No selective damage to nerve head capillaries is seen in mildly damaged specimens. Scanning electron microscopic analysis suggests that the structure of the lamina cribrosa is an important determinant of the degree of susceptibility to damage by elevated intraocular pressure.
                Bookmark

                Author and article information

                Journal
                Mol Vis
                Mol. Vis
                MV
                Molecular Vision
                Molecular Vision
                1090-0535
                2015
                14 July 2015
                : 21
                : 749-766
                Affiliations
                [1]Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA
                Author notes
                Correspondence to: Tatjana C. Jakobs, Schepens Eye Research Institute, 20 Staniford Street Boston, MA, 02114; Phone: (617) 912-0205; FAX: (617) 912-0116; email: Tatjana_Jakobs@ 123456meei.harvard.edu
                Article
                69 2015MOLVIS0047
                4502055
                26236150
                5ee78504-5247-4fe7-9867-41f2ee48b0f4
                Copyright © 2015 Molecular Vision.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited, used for non-commercial purposes, and is not altered or transformed.

                History
                : 28 January 2015
                : 12 July 2015
                Categories
                Research Article
                Custom metadata
                Export to XML

                Vision sciences
                Vision sciences

                Comments

                Comment on this article