期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 116, 期 20, 页码 9989-9998出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1820387116
关键词
microglia; autoimmune uveitis; retina; blood-retinal barrier; systemic leukocytes
资金
- Department of Ophthalmology (Harvard University)
- Massachusetts Eye and Ear Infirmary
- NIH/National Eye Institute [R01EY027303]
- Massachusetts Lions Eye Research Fund
- American Macular Degeneration Foundation Prevention Award
Autoimmune uveitis is a sight-threatening ocular inflammatory condition in which the retina and uveal tissues become a target of autoreactive immune cells. While microglia have been studied extensively in autoimmune uveitis, their exact function remains uncertain. The objective of the current study was to determine whether resident microglia are necessary and sufficient to initiate and amplify retinal inflammation in autoimmune uveitis. In this study, we clearly demonstrate that microglia are essential for initiating infiltration of immune cells utilizing a murine model of experimental autoimmune uveoretinitis (EAU) and the recently identified microglia-specific marker P2ry12. Initiating disease is the primary function of microglia in EAU, since eliminating microglia during the later stages of EAU had little effect, indicating that the function of circulating leukocytes is to amplify and sustain destructive inflammation once microglia have triggered disease. In the absence of microglia, uveitis does not develop, since leukocytes cannot gain entry through the blood-retinal barrier, illustrating that microglia play a critical role in regulating infiltration of inflammatory cells into the retina.
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