日光暴露诱导表观遗传修饰在新疆维吾尔族剥脱综合征发病中的机制研究

Exfoliation syndrome (XFS) is an extracellular matrix metabolic disease, mainly characterized by ocular manifestations. The incidence of glaucoma is as high as 30%, leading to severe visual inpairment. In China, the Uygur of Xinjiang is a high-risk population for XFS. Our previous studies have demonstrated that solar exposure is the risk factor of XFS in the Uygur population, in addition, the methylation of LOXL1 is associated with the pathogenesis of XFS. However, the mechanism of the methylation of LOXL1 in XFS is still not clear. It is verified that the ultraviolet radiation in sunlight is an important inducer for human DNA methylation. Therefore, we hypothesize that excessive solar exposure may induce LOXL1 methylation in the pathogenesis of XFS. We will explore the mechanism of epigenetic modifications induced by solar exposure in the pathogenesis of XFS by the following aspects: to evaluate the association of LOXL1 methylation level with the degeree of solar exposure in XFS patients, to induce the XFS-like phenotype in vitro and in vivo by UV irradiation. This project is based on our previous work, to discover the mystery of the causes of XFS. The performance of the project will help to develop the preventive measures for XFS in future.

剥脱综合征（exfoliation syndrome; XFS）是累及眼部为主的细胞外基质代谢性疾病，青光眼的发生率高达30%，导致视力的严重损害。我国新疆维吾尔族是XFS的好发人群。我们在前期研究中发现日光暴露是维吾尔族XFS的发病危险因素；此外，我们还发现XFS发病与LOXL1基因的甲基化程度有关。但导致XFS患者LOXL1甲基化的具体机制尚不明确。研究证实日光中的紫外线是人体DNA发生甲基化的重要诱导剂。因此，我们推测，XFS发病过程中LOXL1基因的甲基化可能由过度的日光暴露所致。本项目将从分析XFS患者眼部日光暴露程度与LOXL1甲基化水平的关联性、紫外线诱导虹膜色素上皮细胞和实验动物发生XFS样反应等多个层面探索日光暴露诱导的表观遗传学修饰在XFS发病中的具体机制。本项目是我们前期工作的延续，项目的开展将有助于进一步揭开XFS发病原因的神秘面纱，为XFS的早期预防提供科学依据。

剥脱综合征（exfoliation syndrome; XFS）是累及眼部为主的细胞外基质代谢性疾病,青光眼的发生率高达30%，导致视力的严重损害。我国新疆维吾尔族是XFS的好发人群。我们在前期研究中发现日光暴露是维吾尔族XFS的发病危险因素；此外，我们还发现XFS发病与LOXL1基因的甲基化程度有关。但导致XFS患者LOXL1甲基化的具体机制尚不明确。研究证实日光中的紫外线是人体DNA发生甲基化的重要诱导剂。因此，我们推测，XFS发病过程中LOXL1基因的甲基化可能由过度的日光暴露所致。本项目将从分析XFS患者眼部日光暴露程度与LOXL1甲基化水平的关联性、紫外线诱导虹膜色素上皮细胞和实验动物发生XFS样反应等多个层面探索日光暴露诱导的表观遗传学修饰在XFS发病中的具体机制。本项目是我们前期工作的延续，项目的开展将有助于进一步揭开XFS发病原因的神秘面纱，为XFS的早期预防提供科学依据。