B7-H3调控血源性干/祖细胞及巨噬细胞迁移和分化影响脉络膜新生血管发生的机制研究

脉络膜新生血管（CNV）是年龄相关性黄斑变性的严重并发症。发病与多种因素相关。免疫学途径的调控对CNV发病的影响引起高度重视。B7-H3是调节免疫应答、炎症反应以及肿瘤血管发生的关键分子。我们前期研究激光诱导的CNV模型发现，B7-H3基因敲除小鼠的CNV面积下降、脉络膜组织内巨噬细胞和血源性干/祖细胞数目减少，推测B7-H3分子参与调节CNV的发生发展。本项目旨在：①通过体内外实验，分析B7-H3在CNV发生过程中动态表达，对CNV发生的具体作用，对巨噬细胞和血源性干/祖细胞迁移、极化（或分化）的影响以及对脉络膜组织内与血管发生相关的多种细胞因子表达的影响，研究B7-H3参与调节CNV发生发展的具体病理机制。②结合AMD（CNV）患者玻璃体、房水和外周血等样本的检测，综合分析B7-H3与CNV发病的相关性。研究B7-H3作为重要靶分子干预CNV的可能性，并为探讨CNV发病机制提供新思路。

Choroidal neovascularization (CNV) is one of serious complications of age-related macular degeneration. The onset of CNV is related to a variety of factors. The regulation of immunologic pathway on CNV development has aroused great concern. B7-H3 is a key molecular that has the ability to regulating immune response, inflammatory reaction and tumor angiogenesis. Our previous study showed that the area of CNV induced by laser injury was reduced in B7-H3 knockout (KO) mice in comparison with wild type mice. Concomitantly, the numbers of intra-choroidal infiltrated macrophages and bone marrow-derived progenitor cells were also reduced in B7-H3 KO mice when compared to wild type mice. We hence speculate that B7-H3 has an important role in CNV development. The purpose in this project is firstly to investigate the specific pathological mechanism of the involvement of B7-H3 in CNV by carrying out in vivo and in vitro experiments of examining intra-choroidal dynamic expression of B7-H3 in the process of CNV; the effects of B7-H3 on the development of laser-induced CNV; the regulation of B7-H3 on the migration and polarization of macrophages and migration and differentiation of bone marrow-derived progenitor cells; the effects of B7-H3 on intra-choroidal scretion of angiogenic-associated cytokines. Secondly, to analyze the relationship between B7-H3 and the occurrence of CNV with the data obtained from ELISA and/or microarray detection on the samples of vitreous body, aqueous humor and peripheral blood from patients with AMD (and/or with CNV). Therefore, we also evaluate the potential of B7-H3 as a molecular target in clinical intervention and provide novel insight into pathogenesis of CNV.