Thrombospondin-1-mediated regulation of microglia activation after retinal injury.
OBJECTIVE
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.
Ng
Tat Fong
TF
Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Turpie
Bruce
B
Masli
Sharmila
S
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology*; D015703:Antigens, CD / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D005136:Eye Proteins / Q000502:physiology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007834:Lasers / Q000009:adverse effects; D008027:Light / Q000009:adverse effects; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000528:radiation effects*; D012164:Retinal Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019700:Thrombospondin 1 / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015703:Antigens, CD; D015415:Biomarkers; D005136:Eye Proteins; D000949:Histocompatibility Antigens Class II; D019700:Thrombospondin 1; D014409:Tumor Necrosis Factor-alpha; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse