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Xiaoshuang Jiang, Yingqin Ni, Ge-zhi Xu; Powerful Beneficial Effects of Macrophage Colony-stimulating Factor on Retinal Microglia Proliferation and Vascular Repair in the Mouse Model of Oxygen-Induced Retinopathy. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5589.
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Studies confirmed that microglia and/or its progenitor transplantation can increase the rate of intraretinal revascularization in ischemic retinopathies. But cell transplantation source is limited and allogenic rejection may be inevitable. Macrophage colony-stimulating factor (M-CSF) is the main regulator of proliferation of microglia. We investigated whether more microglia, produced by stimulation of M-CSF, can accelerate revascularization in oxygen-induced retinopathy (OIR).
C57BL/6J mice were exposed to 75%±3% oxygen (P7-P12), to initiate OIR and received intraperitoneal injections of M-CSF on P12. The microglia and vasculature of retinas were labeled with CD11b antibody and Griffonia simplicifolia. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to analyze the mRNA of CD11b. Western blot was applied to evaluate CD11b, ZO-1, occludin and MMP-9.
Immunohistochemistry showed injection of M-CSF induced retinal microglia proliferation and avascular area reduction in OIR. RT-PCR analysis revealed that the mRNA of CD11b were elevated 3.16 fold, 3.24 fold and 2.05 fold and western blot showed the protein were elevated 3.2 fold, 2.1 fold and 2.4 fold in the M-CSF-treated OIR mice compared with control OIR at P15, P17 and P21. Compared with normal retina, OIR retina showed a significant reduction by 55%, 29%, 36% of ZO-1 expression at P15, P17 and P21, but M-CSF-injected OIR retina showed a reduction by 35%, 2%, 36%; No significant difference was detected for occludin expression. For expression of MMP-9, OIR retina has a increasion by 1.82 fold, 3.91 fold, 1.91 fold compared with normal retina at P15, P17, P21, while M-CSF-injected OIR retina has a less increasion by 2.26 fold ,1.43 fold at P15, P17, and a similar protein level at P21.
Retinal microglia can proliferate by being stimulated by M-CSF, and it can promote the process of revascularization and formation of blood retinal barrier’ integrity in OIR models.
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