HTR1D基因在原发性先天性青光眼发病机制中的功能研究

Primary congenital glaucoma （PCG）is one of the major cause of blindness and many patients are suffering from it. Also, There is no convincing responsible genes identified yet and no precaution and treatment available for PCG. Therefore, it is very important to reveal its etiology and pathological mechanism. This study is to screen gene mutations by enlarging PCG samples in HTR1D gene which has been identified in our previous study. mRNA expression and localization of this gene in human tissue are determined by RT-PCR, in situ hybridization and immunohistochemistry, respectively. Cell biology research will be performed to explore the effect of this mutation on HTR1D gene in vitro. The pathogenic mechanism of PCG will be investigated by zebrafish and knockout mice model in vivo. This study is to examine the function of HTR1D gene in PCG and reveal the role of this gene in PCG, which could provide new approaches and targets for disease prevention, prenatal diagnosis and treatment, and also have an important role in clinical drug development.

原发性先天性青光眼（Primary congenital glaucoma，PCG）是主要致盲眼病之一，严重影响患者生存质量。迄今为止尚无明确公认的PCG的致病基因,缺乏有效的预防和治疗手段。对其病因、病理机制的研究是解决PCG问题的关键。本研究拟在前期研究发现的一个新的PCG致病基因-HTR1D的基础上，扩大样本鉴定该基因在PCG病人中的突变情况；通过RT-PCR、原位杂交、免疫组化等方法检测其表达情况；体外细胞生物学研究突变体对该基因功能的影响；并通过斑马鱼和基因敲除小鼠模型体内研究其致病机制。本研究旨在明确HTR1D的基因功能及其在PCG发生发展过程中的作用，为PCG预防、产前诊断和治疗奠定基础，同时疾病基因产物可作为有价值的靶标以开发新药。

原发性先天性青光眼（PCG）是严重影响患者生存质量的致盲性眼病之一，对其病因、病理机制的研究是解决PCG 问题的关键。本研究在前期研究HTR1D的基础上，扩大样本鉴定该基因在PCG 病人中的突变情况，初步排除HTR1D基因在PCG发病中的作用，通过运用全基因组外显子测序,并进行Sanger测序验证，对WDR64、PXDN 、FOXC1、 ATP6AP1等基因突变进行了深入探讨，初步筛选出ATP6AP1基因可能与PCG发病有关。通过Western Blot、免疫细胞化学等方法检测其表达情况，体外细胞生物学研究突变体对该基因功能的影响。本项目研究疾病基因功能及其在PCG 发生发展过程中的作用，为PCG 预防、产前诊断和治疗奠定基础。