title: Müller cell reactivity in response to photoreceptor degeneration in rats with defective polycystin-2.
abstract: BACKGROUND
  Retinal degeneration in transgenic rats that express a mutant cilia gene polycystin-2 (CMV-PKD2(1/703)HA) is characterized by initial photoreceptor degeneration and glial activation, followed by vasoregression and neuronal degeneration (Feng et al., 2009, PLoS One 4: e7328). It is unknown whether glial activation contributes to neurovascular degeneration after photoreceptor degeneration. We characterized the reactivity of Müller glial cells in retinas of rats that express defective polycystin-2.
  
  
  METHODS
  Age-matched Sprague-Dawley rats served as control. Retinal slices were immunostained for intermediate filaments, the potassium channel Kir4.1, and aquaporins 1 and 4. The potassium conductance of isolated Müller cells was recorded by whole-cell patch clamping. The osmotic swelling characteristics of Müller cells were determined by superfusion of retinal slices with a hypoosmotic solution.
  
  
  RESULTS
  Müller cells in retinas of transgenic rats displayed upregulation of GFAP and nestin which was not observed in control cells. Whereas aquaporin-1 labeling of photoreceptor cells disappeared along with the degeneration of the cells, aquaporin-1 emerged in glial cells in the inner retina of transgenic rats. Aquaporin-4 was upregulated around degenerating photoreceptor cells. There was an age-dependent redistribution of Kir4.1 in retinas of transgenic rats, with a more even distribution along glial membranes and a downregulation of perivascular Kir4.1. Müller cells of transgenic rats displayed a slight decrease in their Kir conductance as compared to control. Müller cells in retinal tissues from transgenic rats swelled immediately under hypoosmotic stress; this was not observed in control cells. Osmotic swelling was induced by oxidative-nitrosative stress, mitochondrial dysfunction, and inflammatory lipid mediators.
  
  
  CONCLUSIONS
  Cellular swelling suggests that the rapid water transport through Müller cells in response to osmotic stress is altered as compared to control. The dislocation of Kir4.1 will disturb the retinal potassium and water homeostasis, and osmotic generation of free radicals and inflammatory lipids may contribute to neurovascular injury.
authors.affiliation: Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Vogler
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Margrit
authors.initials: M
authors.lastname: Hollborn
authors.forename: Antje
authors.initials: A
authors.lastname: Grosche
authors.forename: Stephanie
authors.initials: S
authors.lastname: Busch
authors.forename: Sigrid
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hammes
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000375:Aging / Q000473:pathology; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D051401:Aquaporin 4 / Q000235:genetics / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002469:Cell Separation; D063928:Ependymoglial Cells / Q000378:metabolism* / Q000473:pathology*; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D009995:Osmosis; D018384:Oxidative Stress; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D017207:Rats, Sprague-Dawley; D012162:Retinal Degeneration / Q000378:metabolism / Q000473:pathology*; D050396:TRPP Cation Channels / Q000378:metabolism*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D051398:Aquaporin 1; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D005974:Glutamate-Ammonia Ligase; D018836:Inflammation Mediators; D064231:Nestin; D024661:Potassium Channels, Inwardly Rectifying; D050396:TRPP Cation Channels; D014746:Vimentin