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Publication : Thrombospondin-1-mediated regulation of microglia activation after retinal injury.

First Author  Ng TF Year  2009
Journal  Invest Ophthalmol Vis Sci Volume  50
Issue  11 Pages  5472-8
PubMed ID  19494207 Mgi Jnum  J:154654
Mgi Id  MGI:4397664 Doi  10.1167/iovs.08-2877
Citation  Ng TF, et al. (2009) Thrombospondin-1-mediated regulation of microglia activation after retinal injury. Invest Ophthalmol Vis Sci 50(11):5472-8
abstractText  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.
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