PMID- 17525210
OWN - NLM
STAT- MEDLINE
DCOM- 20070702
LR  - 20181113
IS  - 0146-0404 (Print)
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 48
IP  - 6
DP  - 2007 Jun
TI  - Attenuated glial reactions and photoreceptor degeneration after retinal 
      detachment in mice deficient in glial fibrillary acidic protein and vimentin.
PG  - 2760-8
AB  - PURPOSE: To characterize the reactions of retinal glial cells (astrocytes and 
      Muller 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.
FAU - Nakazawa, Toru
AU  - Nakazawa T
AD  - Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Harvard Medical 
      School, Boston, MA 02114, USA.
FAU - Takeda, Masumi
AU  - Takeda M
FAU - Lewis, Geoffrey P
AU  - Lewis GP
FAU - Cho, Kin-Sang
AU  - Cho KS
FAU - Jiao, Jianwei
AU  - Jiao J
FAU - Wilhelmsson, Ulrika
AU  - Wilhelmsson U
FAU - Fisher, Steven K
AU  - Fisher SK
FAU - Pekny, Milos
AU  - Pekny M
FAU - Chen, Dong F
AU  - Chen DF
FAU - Miller, Joan W
AU  - Miller JW
LA  - eng
GR  - EY014104/EY/NEI NIH HHS/United States
GR  - EY00888/EY/NEI NIH HHS/United States
GR  - R01 EY017641-01A2/EY/NEI NIH HHS/United States
GR  - R37 EY000888/EY/NEI NIH HHS/United States
GR  - R01 EY012983/EY/NEI NIH HHS/United States
GR  - EY003790/EY/NEI NIH HHS/United States
GR  - P30 EY014104/EY/NEI NIH HHS/United States
GR  - P30 EY003790/EY/NEI NIH HHS/United States
GR  - R01 EY017641/EY/NEI NIH HHS/United States
GR  - R01 EY000888/EY/NEI NIH HHS/United States
GR  - EY012983/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Vimentin)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Chemokine CCL2/metabolism
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fluorescent Antibody Technique, Indirect
MH  - Glial Fibrillary Acidic Protein/deficiency/*physiology
MH  - Gliosis/etiology/metabolism/prevention & control
MH  - In Situ Nick-End Labeling
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microglia/physiology
MH  - Monocytes/physiology
MH  - Neuroglia/*physiology
MH  - Photoreceptor Cells, Vertebrate/pathology
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Retina/*pathology
MH  - Retinal Degeneration/etiology/metabolism/*prevention & control
MH  - Retinal Detachment/*complications
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Vimentin/deficiency/*physiology
PMC - PMC2613948
MID - NIHMS82477
EDAT- 2007/05/26 09:00
MHDA- 2007/07/03 09:00
PMCR- 2009/01/05
CRDT- 2007/05/26 09:00
PHST- 2007/05/26 09:00 [pubmed]
PHST- 2007/07/03 09:00 [medline]
PHST- 2007/05/26 09:00 [entrez]
PHST- 2009/01/05 00:00 [pmc-release]
AID - 48/6/2760 [pii]
AID - 10.1167/iovs.06-1398 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2007 Jun;48(6):2760-8. doi: 10.1167/iovs.06-1398.