αA Crystallin May Protect against Geographic Atrophy—Meta-Analysis of Cataract vs. Cataract Surgery for Geographic Atrophy and Experimental Studies

BackgroundCataract and geographic atrophy (GA, also called advanced “dry” age-related macular degeneration) are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies.
Methods/Principal FindingsWe performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR) of 3.75 (95% CI: 95% CI: 1.84–7.62). However, cataract surgery is not associated with the risk of geographic atrophy (polled OR = 3.23, 95% CI: 0.63–16.47). Further experiments were performed to analyze how the αA-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that theαA-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO3 in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in αA-crystallin knockout mice compared to wild-type mice.
ConclusionsTherefore, αA-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA.

背景：白内障与地理性萎缩（geographic atrophy, GA，又称进展性"干性"年龄相关性黄斑变性（age-related macular degeneration））是发达国家两大主要视力损伤诱因。既往研究中，白内障手术与地理性萎缩发病的关联曾存在争议。
方法与主要结果：我们通过整合当前文献中的证据开展了一项荟萃分析（meta-analysis），结果显示白内障与地理性萎缩的发病风险升高相关，汇总比值比（odds ratio, OR）为3.75（95%置信区间（confidence interval, CI）：1.84~7.62）。但白内障手术与地理性萎缩的发病风险并无关联（合并OR=3.23，95%CI：0.63~16.47）。后续我们开展了进一步实验，在小鼠模型（mouse model）中分析晶状体主要成分αA-晶状体蛋白（αA-crystallin）对地理性萎缩发病的影响。通过视网膜切片免疫组化（immunohistochemistry）及后眼杯蛋白质免疫印迹（western blot）实验，我们发现NaIO3诱导氧化应激后，αA-晶状体蛋白的mRNA与蛋白表达水平均升高。功能与组织病理学证据均证实，αA-晶状体蛋白敲除（knockout）小鼠的地理性萎缩症状较野生型（wild-type）小鼠更为严重。
结论：因此，αA-晶状体蛋白可能对地理性萎缩具有保护作用。本研究进一步阐明了白内障、白内障手术与地理性萎缩三者之间的关联。