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      The outer limiting membrane (OLM) revisited: clinical implications

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          Abstract

          Purpose

          The outer limiting membrane (OLM) is considered to play a role in maintaining the structure of the retina through mechanical strength. However, the observation of junction proteins located at the OLM and its barrier permeability properties may suggest that the OLM may be part of the retinal barrier.

          Material and methods

          Normal and diabetic rat, monkey, and human retinas were used to analyze junction proteins at the OLM. Proteome analyses were performed using immunohistochemistry on sections and flat-mounted retinas and western blotting on protein extracts obtained from laser microdissection of the photoreceptor layers. Semi-thin and ultrastructure analyses were also reported.

          Results

          In the rat retina, in the subapical region zonula occludens-1 (ZO-1), junction adhesion molecule (JAM), an atypical protein kinase C, is present and the OLM shows dense labeling of occludin, JAM, and ZO-1. The presence of occludin has been confirmed using western blot analysis of the microdissected OLM region. In diabetic rats, occludin expression is decreased and glial cells junctions are dissociated. In the monkey retina, occludin, JAM, and ZO-1 are also found in the OLM. Junction proteins have a specific distribution around cone photoreceptors and Müller glia. Ultrastructural analyses suggest that structures like tight junctions may exist between retinal glial Müller cells and photoreceptors.

          Conclusions

          In the OLM, heterotypic junctions contain proteins from both adherent and tight junctions. Their structure suggests that tight junctions may exist in the OLM. Occludin is present in the OLM of the rat and monkey retina and it is decreased in diabetes. The OLM should be considered as part of the retinal barrier that can be disrupted in pathological conditions contributing to fluid accumulation in the macula.

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          Author and article information

          Journal
          Clin Ophthalmol
          Clinical Ophthalmology
          Clinical Ophthalmology (Auckland, N.Z.)
          Dove Medical Press
          1177-5467
          1177-5483
          2010
          2010
          26 April 2010
          : 4
          : 183-195
          Affiliations
          [1 ] INSERM, U872 Physiopathology of ocular diseases: Therapeutic innovations, Paris, France
          [2 ] Centre de Recherche des Cordeliers, Université Pierre et Marie Curie – Paris6, Paris, France
          [3 ] Université Paris Descartes, Paris, France
          [4 ] Department of Ophthalmology, Hôtel-Dieu de Paris, France
          [5 ] Department of Ophthalmology, Bellevue Hospital, University of Saint-Etienne, France
          Author notes
          Correspondence: Francine Behar-Cohen, Tel +33 01 40 46 78 46, Fax +33 01 40 46 78 59, Email francine.behar@ 123456gmail.com
          Article
          opth-4-183
          10.2147/opth.s5901
          2861922
          20463783
          c4e36398-ea35-4ddc-a7bd-93feaa05efa2
          © 2010 Omri et al, publisher and licensee Dove Medical Press Ltd.

          This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

          History
          Categories
          Original Research

          Ophthalmology & Optometry
          adherent,junctions,retinal barrier,tight,olm,diabetes
          Ophthalmology & Optometry
          adherent, junctions, retinal barrier, tight, olm, diabetes

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