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Ryo Mukai, Yoko Okunuki, Clifford Kim, Dong Ho Park, Deeba Husain, Kip M Connor; Microglial development in the eye and brain. Invest. Ophthalmol. Vis. Sci. 2018;59(9):580. doi: https://doi.org/.
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Microglia are the resident immune cells of the CNS, including the retina, and function in the homeostatic maintenance of the neuro-retinal microenvironment. In healthy eyes, microglia are typically located in the plexiform layers of the retina. However, to date a challenge has been to distinguish resident microglia from recruited monocytes during neuroinflammation, although until recently no unique microglial surface markers have existed to allow this distinction. Here we utilize the microglial specific marker P2ry12 and define microglial distribution in the eye and brain during early development of the mouse[Office1] .We also reveal the function of colony stimulating factor 1 receptor (CSF1R) system during microglial development in those tissues.
Utilizing CX3CR1 +/GFP embryos from embryonic (E) days 9.5 to E 17.5, we illustrate the distribution of monocytes and microglia (stained with P2ry12). In addition, we also assess the effect of microglial depletion, using a csfl1r antagonist during development.
GFP positive cells were initially distributed in the optic cup and neural ectoderm at E9.5, and those GFP positive cells stained with P2ry12, which is a newly developed microglial specific marker, appeared to migrate into optic stalk and optic cup at E11.5. The pattern of distributed GFP positive cells were round with numerous vesicles in their cytosol at E11.5, however once those cells reached the optic cup, they distributed directionally from inferior to superior of the optic cup, and exhibited elongated ramified processes. These cells appeared to migrate from neural ectoderm to optic cup and accomplish this independent of the vascular system, but through neural structures directly. Oral administration of Csf1r antagonist, strongly suppressed migration of GFP positive cells into the optic cup and brain and completely inhibited distribution of P2ry12 positive cells in those tissues. However a small number of GFP positive cells did distribute within the eye and brain even under csf1r inhibition.
Our result suggested that (1) P2ry12 positive microglial distribution in the eye and brain begin at E10.5 to 11.5, and (2) P2ry12 positive microglial cells were significantly regulated by CSF-1R signaling system however proliferation in some of GFP positive populations in the brain may be independent from CSF-1R system.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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