Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, People's Republic of China.
NHC Key Laboratory of Myopia, Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Fudan University, Shanghai 200031, People's Republic of China.
Aging (Albany NY). 2021 Jun 7;13(11):15255-15268. doi: 10.18632/aging.203086.
Cataract is the leading cause of visual impairment globally. Racemization of lens proteins may contribute to cataract formation in aging individuals. As a special type of age-related cataract (ARC), diabetic cataract (DC) is characterized by the early onset of cortical opacification and finally developed into a mixed type of cortical and nuclear opacification. We compared racemization of Asp 58 residue, a hotspot position in αA-crystallin, from the cortex and nucleus of diabetic and age-matched senile cataractous lenses, by identifying L-Asp/L-isoAsp/D-Asp/D-isoAsp by mass spectrometry. Compared to nondiabetic cataractous lenses, DC lenses showed a significantly increased cortex/nucleus ratio of D-Asp 58, which originated primarily from an increased percentage of D-Asp 58 in the lens cortex of DC. Moreover, patients diagnosed with diabetes for over 10 years showed a lower cortex/nucleus ratio of D-isoAsp 58 in the lens compared with those who had a shorter duration of diabetes, which originated mainly from an increased percentage of D-isoAsp 58 in the lens nucleus of DC with increasing time of hyperglycemia. Further analysis confirmed decreased protein solubility in diabetic cataractous lenses. The different racemization pattern in DC may be distinguished from ARC and influence its phenotype over the protracted duration of diabetes.
白内障是全球范围内导致视力损害的主要原因。晶状体蛋白的外消旋化可能导致衰老个体白内障的形成。作为一种特殊类型的年龄相关性白内障（ARC），糖尿病性白内障（DC）的特征是皮质混浊的早期发生，最终发展为皮质和核混浊的混合类型。我们通过质谱法鉴定 L-Asp/L-isoAsp/D-Asp/D-isoAsp，比较了来自糖尿病和年龄匹配的老年性白内障晶状体皮质和核中αA-晶体蛋白热点位置 Asp58 残基的外消旋化。与非糖尿病性白内障晶状体相比，DC 晶状体的 D-Asp58 皮质/核比值显著增加，这主要来源于 DC 晶状体皮质中 D-Asp58 的百分比增加。此外，与糖尿病病程较短的患者相比，被诊断患有糖尿病超过 10 年的患者的晶状体中 D-isoAsp58 的皮质/核比值较低，这主要来源于 DC 晶状体核中 D-isoAsp58 的百分比增加，这与高血糖时间的延长有关。进一步的分析证实了糖尿病性白内障晶状体中蛋白质溶解度降低。DC 中的不同外消旋化模式可能与 ARC 区分开来，并影响其在糖尿病漫长病程中的表型。
