Thrombospondin-1 mediated regulation of microglia activation after retinal injury
Tatfong Ng 1,
Bruce Turpie 1,
and
Sharmila Masli 2*
1 Schepens Eye Research Institute, Boston, Massachusetts, United States
2 Department of Ophthalmology, Schepens Eye Research Institute/Harvard Medical School, Boston, Massachusetts, United States
* To whom correspondence should be addressed. E-mail: sharmila.masli{at}schepens.harvard.edu.
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Abstract |
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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 pro-inflammatory and regenerative neurotrophic factors. In this study we examine 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 semi-quantitative real-time PCR analysis of retina derived from either WT or TSP-1null mice at various time intervals after light or laser-induced retinal injury.
Results : In the absence of TSP-1 microglia in uninjured retina express MHC class II and migrate to the outer layers of the retina. Constitutively increased expression of activated microglia-derived inflammatory molecules such as TNF- 
and iNOS is detectable in TSP-1null retina as compared to WT controls. Following both light-induced and laser-induced retinal injury, enhanced migration of microglia is detected in TSP-1null retina and these microglia express markers associated with a pro-inflammatory phenotype. Compared to WT retina, TSP-1null retina fails to recover from the laser-induced injury resulting in irreversible damage.
Conclusion : Thrombospondin supports an anti-inflammatory phenotype of microglia in the retina and promotes recovery from injury.
Key Words:
immune privilege, macrophages, retinal cell differentiation, light damage, retinal degeneration
