Research Paper Volume 13, Issue 11 pp 15255—15268
Racemization in cataractous lens from diabetic and aging individuals: analysis of Asp 58 residue in αA-crystallin
- 1 Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, People’s Republic of China
- 2 NHC Key Laboratory of Myopia, Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Fudan University, Shanghai 200031, People’s Republic of China
- 3 Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, People’s Republic of China
Received: July 24, 2020 Accepted: April 29, 2021 Published: June 7, 2021https://doi.org/10.18632/aging.203086
How to Cite
Copyright: © 2021 Zhu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
ARC: age-related cataract; DC: diabetic cataract; PTMs: posttranslational modifications; L-Asp: L-aspartyl; L-isoAsp: L-isoaspartyl; D-Asp: D-aspartyl; D-isoAsp: D-isoaspartyl; LOCSIII: lens opacity classification system III; RP-HPLC: reversed-phase high performance liquid chromatography; LC: liquid chromatography; ESI: electrospray ionization; MS: mass spectrometry; UPLC: ultra-performance liquid chromatography. DTT: dithiothreitol; BCA: bicinchoninic acid; UA: uric acid; SD: standard deviations.