ICE综合征继发性青光眼病因初探及miR-30a-3p调控角膜内皮细胞迁移在其发病中的机制研究

ICE综合征属于眼科罕见病、致盲病。病因未明。我们前期研究发现：1）ICE继发性青光眼房水中存在多种miRNA差异表达，其中miR-30a-3p表达增加；2）miR-30a-3p可诱导角膜内皮细胞病变，与细胞增殖、迁移密切相关，同时影响下游靶基因N-cadherin的表达；3）利用已建立的国内多中心ICE罕见病数据库，全基因组测序结果显示ICE存在特定基因突变特征。基于此，提出假说：1）miR-30a-3p/N-cadherin通路介导的角膜内皮细胞增殖、迁移参与ICE继发性青光眼的发生；2）ICE可能存在特定遗传基础。本项目拟联合全国多家医院完善ICE罕见病数据库，通过全基因组测序，探索ICE的遗传特征；以临床样本结合体内外实验，采用高通量测序、miRNA干预结合分子生物学技术，探索上述通路介导的角膜内皮细胞病变在ICE及继发性青光眼中的作用，有望揭示ICE新的发病机制及有效的干预靶点。

Iridocorneal endothelial (ICE) syndrome is a rare ocular disease with unknown etiology which causes blindness. Our pilot studies found that: 1) the microRNA expression features in aqueous humor of ICE syndrome eyes with secondary glaucoma were different to controls; among them, miR-30a-3p was significantly elevated; 2) miR-30a-3p could induce abnormal proliferation and migration of corneal endothelial cells, and regulate expression of its target gene N-cadherin; 3) we have established a domestic multi-center consortium on ICE study, and found specific mutation features of ICE patients via performing the whole genome sequencing. On the strength of the above discoveries, we put forward our hypotheses: 1) miR-30a-3p/N-cadherin pathway mediates the proliferation and migration of corneal endothelial cells, which is involved in ICE secondary glaucoma; 2) specific genetic predisposition is associated with ICE etiology. In this research we will develop ICE Rare Disease Database in cooperation with dozens of hospitals nationwide, explore genetic features of ICE via using the whole genome sequencing, and try to clarify the roles of miR-30a-3p/N-cadherin pathway in ICE secondary glaucoma via next-generation RNA sequencing, microRNA intervention and molecular biotechnologies. Therefore, this study will promisingly shed light on ICE pathogenesis and provides new therapy targets for ICE treatment.