title: Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin.
abstract: OBJECTIVE
  To characterize the reactions of retinal glial cells (astrocytes and Müller cells) to retinal injury in mice that lack glial fibrillary acidic protein (GFAP) and vimentin (GFAP-/-Vim-/-) and to determine the role of glial cells in retinal detachment (RD)-induced photoreceptor degeneration.
  
  
  METHODS
  RD was induced by subretinal injection of sodium hyaluronate in adult wild-type (WT) and GFAP-/-Vim-/- mice. Astroglial reaction and subsequent monocyte recruitment were quantified by measuring extracellular signal-regulated kinase (Erk) and c-fos activation and the level of expression of chemokine monocyte chemoattractant protein (MCP)-1 and by counting monocytes/microglia in the detached retinas. Immunohistochemistry, immunoblotting, real-time quantitative polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) were used. RD-induced photoreceptor degeneration was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) and measurement of outer nuclear layer (ONL) thickness.
  
  
  RESULTS
  RD-induced reactive gliosis, characterized by GFAP and vimentin upregulation, Erk and c-fos activation, MCP-1 induction, and increased monocyte recruitment in WT mice. Absence of GFAP and vimentin effectively attenuated reactive responses of retinal glial cells and monocyte infiltration. As a result, detached retinas of GFAP-/-Vim-/- mice exhibited significantly reduced numbers of TUNEL-positive photoreceptor cells and increased ONL thickness compared with those of WT mice.
  
  
  CONCLUSIONS
  The absence of GFAP and vimentin attenuates RD-induced reactive gliosis and, subsequently, limits photoreceptor degeneration. Results of this study indicate that reactive retinal glial cells contribute critically to retinal damage induced by RD and provide a new avenue for limiting photoreceptor degeneration associated with RD and other retinal diseases or damage.
authors.affiliation: Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Masumi
authors.initials: M
authors.lastname: Takeda
authors.forename: Geoffrey P
authors.initials: GP
authors.lastname: Lewis
authors.forename: Kin-Sang
authors.initials: KS
authors.lastname: Cho
authors.forename: Jianwei
authors.initials: J
authors.lastname: Jiao
authors.forename: Ulrika
authors.initials: U
authors.lastname: Wilhelmsson
authors.forename: Steven K
authors.initials: SK
authors.lastname: Fisher
authors.forename: Milos
authors.initials: M
authors.lastname: Pekny
authors.forename: Dong F
authors.initials: DF
authors.lastname: Chen
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000172:deficiency / Q000502:physiology*; D005911:Gliosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000502:physiology; D009000:Monocytes / Q000502:physiology; D009457:Neuroglia / Q000502:physiology*; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012160:Retina / Q000473:pathology*; D012162:Retinal Degeneration / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D012163:Retinal Detachment / Q000150:complications*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014746:Vimentin / Q000172:deficiency / Q000502:physiology*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D005904:Glial Fibrillary Acidic Protein; D016760:Proto-Oncogene Proteins c-fos; D014746:Vimentin; D048049:Extracellular Signal-Regulated MAP Kinases