Fms-like tyrosine kinase 3 (Flt3), a tyrosine kinase receptor expressed in CD34+ hematopoietic stem/progenitor cells, is important\nfor both normal myeloid and lymphoid differentiation. It has been implicated in mice and humans for potential multilineage\ndifferentiation. We found that mice deficient in Flt3 or mice that received an Flt3 inhibitor (AC220) showed significantly\nreduced areas of ischemia-induced retinal neovascularization (RNV) and laser-induced choroidal NV (CNV) (P < 0 05).\nIncreased Flt3 expression at the protein level was detected in retinas of oxygen-induced retinopathy (OIR) mice at P15 and P18\nduring retinal NV (RNV) progression. We subsequently found that macrophages (Mphi) polarization was regulated at the site\nof CNV in Flt3-deficient mice. Flow cytometry analysis demonstrated that Flt3 deficiency shifted Mphi polarization towards an\nM2 phenotype during RNV with significant reduction in M1 cytokine expression when compared to the wild-type controls\n(P < 0 05). Based on the above findings, we concluded that Flt3 inhibition alleviated ocular NV by promoting a Mphi\npolarization shift towards the M2 phenotype. Therapies targeting Flt3 may provide a new approach for the treatment of ocular NV.
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