视网膜色素变性并发特征性前囊膜下白内障的分子基础

视网膜色素变性(RP)常导致后囊下型（PSC）并发性白内障，课题组经长期临床观察发现前囊下型(ASC)也较多见，表现为特征性的瞳孔区前囊下混浊。现有研究表明RP导致感光细胞变性、降解可引起眼内炎症因子和细胞因子表达增加。我们认为感光细胞代谢产物累积于晶状体和房水中引起眼内微环境变化，可能导致在光照情况下发生晶状体上皮细胞（LEC）增殖分化和上皮间质转化（EMT），导致瞳孔区ASC。本课题选择RP并发ASC需进行手术治疗的病例，首先检测晶状体前囊膜LEC增殖分化与EMT信号表达变化；并且测定房水中炎症因子和生长因子的表达水平以及感光细胞视紫红质的代谢产物维甲酸等含量变化，结合术中房水及晶状体中氧分压差异测定，综合分析ASC发生的相关分子基础。同时进一步检测LEC的基因表达谱、miRNA表达谱和基因组DNA甲基化变化水平，明确RP病程中导致LEC增殖分化和EMT的信号转导调控途径。

Posterior subcapsular opacity（PSC）derived from retinitis pigmentosa(RP) are common in practice. However, with our long-term observation, anterior subcapsular cataract (ASC) arising in RP was thought to be another typical manifestation of this disease. This type of subcapsular opacity was located in the central anterior field of lens just in correspondence with the pupil area. Previous studies reported an increased concentration of inflammatory factors or cytokines in aqueous humor in RP cases. We infer that the molecular mechanism of ASCs, which is characteristically located in the pupil zone, involved in proliferation, differentiation and epithelial-mesenchymal transition of the anterior lens epithelial cells (LECs). Besides, it may be connected to the change of lens metabolism and nutrition microenvironment as a result of the inflammatory reaction in retinitis pigmentosa. And most importantly, the featured location of ASC may be closely related to the rhodopsin metabolite accumulation from photoreceptors apoptosis and retinal pigment epithelium dysfunction.We propose that abnormal cell signaling pathway was stimulated by the metabolite which was activated by rays of light in pupillary zone. In this study, detailed clinical data of retinitis pigmentosa with ASC were recorded. Aqueous humor, capsulorhexis specimans and some cortex from the cases that underwent phacoemulsification were obtained during operation. The markers of EMT and proliferation in LECs are planed to be detected by immunocytochemistry and immunofluorescence techniques. To have a further investigation on the molecular mechanism(s) of ASCs in RP patients, inflammatory factors, cytokines levels and retinoic acid (RA) concentrations in aqueous homor will be measured. The ocular partial pressure of oxygen (PO2) is also to be determined in anterior chamber, and in lens. Besides, the gene expression profiling, microRNA sequencing and DNA methylation in the LECs will be determined and analyzed using bioinformatics platform. All those are performed to find out the molecular biological mechanism(s) of ASCs and to analyze the key pathogenic factor(s) of ASCs formation. We looking forward to provide a valuable target for non-operative interference and make a contribution to a new attempt for preservation of residual visual acuity in retinitis pigmentosa population on the basis of our study.