title: First responders: dynamics of pre-gliotic Müller cell responses in the isolated adult rat retina.
abstract: OBJECTIVE
  To explore the early reactions of the retinal Müller glia in response to retinal insult prior to gliotic remodeling and the sustained upregulation of intermediate filament glial fibrillary acidic protein (GFAP), which has traditionally been considered the most sensitive early indicator of reactive gliosis.
  
  
  METHODS
  To study pre-gliotic events, we used a model of adult rat retinal explants and related the dynamic expression of GFAP as well as apoptosis, to four key regulators of retinal homeostasis (glutamine synthetase (GS), cellular retinaldehyde binding protein (CRALBP), basic fibroblast growth factor (bFGF), carbonic anhydrase II (CAII)) using immunohistochemistry.
  
  
  RESULTS
  We found that a sustained GFAP upregulation couple with gliotic remodeling occurred comparatively late and that this phenomenon was preceded by an initial upregulation followed by depletion of GS, CRALBP, bFGF and CAII in retinal Müller cells. The initial increase of the regulatory proteins, seen after 1-12 h, preceded a first phase of moderate apoptosis, and their depletion after 48 h was followed by massive apoptosis and widespread GFAP upregulation in the Müller cells at 5 days.
  
  
  CONCLUSIONS
  We conclude that, in the explant model, changes in the expression of the four homeostatic regulatory proteins as well as apoptotic cell death precedes sustained GFAP upregulation and reactive gliosis. Müller cell reactivity has been linked to several retinal conditions, and the herein provided novel information on the dynamics of pre-gliotic events in the lesioned retina may help us understand important pathological mechanisms crucial for future therapeutic intervention.
authors.affiliation: a Department of Ophthalmology , Lund University Hospital , Lund , Sweden.
authors.forename: Linnéa
authors.initials: L
authors.lastname: Taylor
authors.affiliation: a Department of Ophthalmology , Lund University Hospital , Lund , Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Arnér
authors.affiliation: a Department of Ophthalmology , Lund University Hospital , Lund , Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D017209:Apoptosis; D024402:Carbonic Anhydrase II / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D063928:Ependymoglial Cells / Q000378:metabolism / Q000473:pathology*; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism*; D005911:Gliosis / Q000378:metabolism / Q000473:pathology*; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
chemical_list: C020932:11-cis-retinal-binding protein; D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D016222:Fibroblast Growth Factor 2; D024402:Carbonic Anhydrase II; D005974:Glutamate-Ammonia Ligase
keywords: Adult retina; GFAP; Müller cells; pre-gliotic; retinal explants; retinal injury