Document Detail


Thrombospondin-1-mediated regulation of microglia activation after retinal injury.
MedLine Citation:
PMID:  19494207     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Thrombospondin (TSP)-1 has been demonstrated to play a vital role in immune privilege. The functional phenotype of ocular antigen-presenting cells that contributes to the immune privilege status of the eye is dependent on their expression of TSP-1. Microglia, the local antigen-presenting cells in the retina, undergo rapid activation in response to injury and have the ability to produce both proinflammatory and regenerative neurotrophic factors. In this study, the authors examined TSP-1 as a potential regulator of these phenotype of microglia activated in response to retinal injury. METHODS: Expression of markers associated with activated microglia were examined by immunofluorescent staining and semiquantitative real-time PCR analysis of retina derived from WT or TSP-1 null mice at various time intervals after light- or laser-induced retinal injury. RESULTS: In the absence of TSP-1, microglia in uninjured retina express major histocompatibility complex class II and migrate to the outer layers of the retina. Constitutively increased expression of activated microglia-derived inflammatory molecules such as TNF-alpha and iNOS is detectable in TSP-1 null retina compared with WT controls. After both light-induced and laser-induced retinal injury, enhanced migration of microglia is detected in TSP-1 null retina, and these microglia express markers associated with a proinflammatory phenotype. Compared with WT retina, TSP-1 null retina fails to recover from the laser-induced injury, resulting in irreversible damage. CONCLUSIONS: TSP-1 supports an anti-inflammatory phenotype of microglia in the retina and promotes recovery from injury.
Authors:
Tat Fong Ng; Bruce Turpie; Sharmila Masli
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-06-03
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  50     ISSN:  1552-5783     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-03     Completed Date:  2009-12-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5472-8     Citation Subset:  IM    
Affiliation:
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigen-Presenting Cells / physiology*
Antigens, CD / metabolism
Biological Markers / metabolism
Cell Movement / physiology
Eye Proteins / physiology*
Female
Fluorescent Antibody Technique, Indirect
Histocompatibility Antigens Class II / metabolism
Lasers / adverse effects
Light / adverse effects
Lymphocyte Activation / physiology
Male
Mice
Mice, Inbred C57BL
Microglia / physiology*
Nitric Oxide Synthase Type II / metabolism
Radiation Injuries, Experimental / etiology,  metabolism*,  pathology
Retina / radiation effects*
Retinal Diseases / etiology,  metabolism*,  pathology
Reverse Transcriptase Polymerase Chain Reaction
Thrombospondin 1 / physiology*
Tumor Necrosis Factor-alpha / metabolism
Grant Support
ID/Acronym/Agency:
EY015472/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Biological Markers; 0/Eye Proteins; 0/Histocompatibility Antigens Class II; 0/Thrombospondin 1; 0/Tumor Necrosis Factor-alpha; EC 1.14.13.39/Nitric Oxide Synthase Type II; EC 1.14.13.39/Nos2 protein, mouse

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