Racemization at the Asp 58 residue in αA‐crystallin from the lens of high myopic cataract patients |
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| Authors: | Xiang‐jia Zhu Ke‐ke Zhang Wen‐wen He Yu Du Michelle Hooi Yi Lu |
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| Affiliation: | 1. Eye Institute, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China;2. Department of Ophthalmology, Eye and ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China;3. Key Laboratory of Myopia, Ministry of Health PR China, Shanghai, China;4. Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai Medical College, Fudan University, Shanghai, China;5. University of Adelaide, Adelaide, SA, Australia |
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| Abstract: | Post‐translational modifications in lens proteins are key causal factors in cataract. As the most abundant post‐translational modification in the lens, racemization may be closely related to the pathogenesis of cataract. Racemization of αA‐crystallin, a crucial structural and heat shock protein in the human lens, could significantly influence its structure and function. In previous studies, elevated racemization from l ‐Asp 58 to d ‐isoAsp58 in αA‐crystallin has been found in age‐related cataract (ARC) lenses compared to normal aged human lenses. However, the role of racemization in high myopic cataract (HMC), which is characterized by an early onset of nuclear cataract, remains unknown. In the current study, apparently different from ARC, significantly increased racemization from l ‐Asp 58 to d ‐Asp 58 in αA‐crystallin was identified in HMC lenses. The average racemization rates for each Asp isoform were calculated in ARC and HMC group. In ARC patients, the conversion of l ‐Asp 58 to d ‐isoAsp 58, up to 31.89%, accounted for the main proportion in racemization, which was in accordance with the previous studies. However, in HMC lenses, the conversion of l ‐Asp 58 to d ‐Asp 58, as high as 35.44%, accounted for the largest proportion of racemization in αA‐crystallin. The different trend in the conversion of αA‐crystallin by racemization, especially the elevated level of d ‐Asp 58 in HMC lenses, might prompt early cataractogenesis and a possible explanation of distinct phenotypes of cataract in HMC. |
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| Keywords: | aspartyl residue cataract crystallin high myopia lens racemization |
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