脉络膜新生血管（CNV）是多种严重致盲性眼病的重要原因，表观遗传调控可能起重要作用，但具体机制尚未完全明确。我们的前期研究表明，CNV过程中可能存在DNA脱甲基化，胞苷脱氨酶APOBEC1很可能起重要作用。据此我们出假说，APOBEC1参与CNV的表观遗传调控，其机制可能是通过介导DNA脱甲基化及RNA编辑，调控相关基因网络，引起炎症反应等并最终导致CNV。为验证假说，我们拟在视网膜/脉络膜内皮细胞及培养组织中沉默和过表达APOBEC1，分析其与DNA脱甲基化和RNA编辑的关系及对相关基因以及细胞形为学的影响;在激光诱导CNV小鼠中利用高通量测序寻找免疫相关基因的脱甲基化靶位点及RNA编辑位点等;以APOBEC1基因敲除小鼠等为动物模型，结合转录组测序和系统生物学研究体内CNV中相关表观遗传调控的基因网络。通过本研究，期望能明确CNV中APOBEC1介导的表观遗传机制，探索新的治疗策略。

Choroidal neovascularization (CNV) is the involved in various vision-threatening eye diseases such as age-related macular degeneration. Epigenetic regulation plays an important role in the development of CNV. Nevertheless, such regulation mechanism has not been fully elucidated. Our preliminary results show that DNA demethylation and a related enzyme APOBEC1 are probably involved in CNV. Therefore, we hypothesize that epigenetics of APOBEC1 is involved in CNV. The mechanism might be that APOBEC1 influences expression of immune response genes by mediating DNA demethylation and RNA-editing and DNA demethylaiton, and eventually leads to CNV. To test this hypothesis, the current proposal attempts to evaluate role of APOBEC1 in DNA demethylation and RNA-editing during CNV. The effects of APOBEC1 on gene expression and cellular behavior will be assessed by overexpression and knockdown of APOBEC1 in vitro in choroidal endothelial cell lines, and mouse retina/choroid explant. RNA-seq will used to characterize RNA-editing sites in transcriptome, and fluorescent polarization and whole-genome bisulfite sequencing genome-wide DNA methylation level and profiling will be used to study the dynamics of DNA demethylation during CNV. Animal models such as APOBEC1 knockout mice will be used to study the effects of APOBEC1 on epigenetics CNV in vivo, and perform gene network analysis using both RNA-seq and system biology approaches. The expected results will unveil the relationship between APOBEC1 and epigenetic regulation of CNV.