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Attenuated glial reactions and photoreceptor degeneration after retinal detachment in mice deficient in glial fibrillary acidic protein and vimentin.

Artikel i vetenskaplig tidskrift
Författare Toru Nakazawa
Masumi Takeda
Geoffrey P Lewis
Kin-Sang Cho
Jianwei Jiao
Ulrika Wilhelmsson
Steven K Fisher
Milos Pekny
Dong F Chen
Joan W Miller
Publicerad i Investigative ophthalmology & visual science
Volym 48
Nummer/häfte 6
Sidor 2760-8
ISSN 0146-0404
Publiceringsår 2007
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för klinisk neurovetenskap och rehabilitering
Sidor 2760-8
Språk en
Länkar dx.doi.org/10.1167/iovs.06-1398
Ämnesord Animals, Blotting, Western, Chemokine CCL2, metabolism, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Extracellular Signal-Regulated MAP Kinases, metabolism, Fluorescent Antibody Technique, Indirect, Glial Fibrillary Acidic Protein, deficiency, physiology, Gliosis, etiology, metabolism, prevention & control, In Situ Nick-End Labeling, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia, physiology, Monocytes, physiology, Neuroglia, physiology, Photoreceptors, Vertebrate, pathology, Proto-Oncogene Proteins c-fos, metabolism, Retina, pathology, Retinal Degeneration, etiology, metabolism, prevention & control, Retinal Detachment, complications, Reverse Transcriptase Polymerase Chain Reaction, Vimentin, deficiency, physiology
Ämneskategorier Neurobiologi

Sammanfattning

PURPOSE: 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.

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