叶黄素和玉米黄素对年龄相关性黄斑病变与视网膜色素上皮细胞氧化损伤的防护作用及其机制研究

Age-related maculopathy (ARM) is a common eye disease leading to blindness, characterized by the degeneration of macular pigment structure and visual function. The five-year rate of vision loss is 35.7%. The early prompt treatment of ARM is essential for preventing the decrease in visual function and improving quality of life. Studies have indicated that oxidative stress plays a crucial role in the pathophysiology of ARM. As the major components of macular pigment, lutein and zeaxanthin have blue-light filtering activities and antioxidant properties. It comes as no surprise that lutein and zeaxanthin may have the beneficial effects on preventing the on set and progression of AMD; however, the exact effect and mechanism are not clear. We will combine population-based studies with laboratory studies in this study. After evaluating the association between level of lutein and zeaxanthin status and ARM risk, we will conduct a intervention study to examine the effect of lutein and zeaxanthin supplementation on macular morphology and visual function. After establishing retinal pigment epithelium (RPE) cell model of oxidative stress, we will study the protective effect and molecular mechanism of lutein and zeaxanthin on cell morphology and phagocytosis. This study will clarify the protective effect and mechanism of lutein and zeaxanthin on ARM, from the molecular, cell, tissue, individual and population, etc, to provide theoretical and experimental basis for the development of drugs for ARM, and to provide new ideas for establishment of ARM intervention strategies and the prevention and control plans.

年龄相关性黄斑病变（ARM）是一种以视网膜黄斑区色素结构和视觉功能退化为特征的常见致盲眼病，五年视力减退率为35.7%，尽早治疗对于遏制视功能下降和改善患者生活质量至关重要。研究已证实其发生与长期氧化损伤密切相关。作为黄斑色素主要成分，叶黄素和玉米黄素可起到抗氧化和滤过蓝光的作用，对ARM具有防治潜力，但其确切作用及其机制尚不清楚。本课题拟将人群研究与实验室研究相结合，在明确机体叶黄素和玉米黄素水平与ARM罹患关系的基础上，对ARM患者进行干预研究，观察叶黄素和玉米黄素干预对患者黄斑形态与视功能所起的作用；建立视网膜色素上皮（RPE）细胞氧化应激模型，探讨叶黄素和玉米黄素对其形态与吞噬功能的保护作用及其分子机制；进而从分子、细胞、组织、个体及群体等多层面，阐明叶黄素和玉米黄素对ARM的防护作用及其机制，为ARM治疗药物的研发提供理论和实验依据，为ARM干预策略与防治方案的建立提供新思路。