关键词: Age-related cataract Cataractogenic load Cholesterol Cholesterol oxidation Eye lens Free radicals Ionising radiation  Lipid rafts Occupational exposure threshold Oxysterol formation Posterior subcapsular cataract Smith-Lemli-Optiz syndrome X-rays

来  源:   DOI:10.1016/j.arres.2022.100057   PDF(Pubmed)

Abstract:
Ionising radiation (IR) is a cause of lipid peroxidation, and epidemiological data have revealed a correlation between exposure to IR and the development of eye lens cataracts. Cataracts remain the leading cause of blindness around the world. The plasma membranes of lens fibre cells are one of the most cholesterolrich membranes in the human body, forming lipid rafts and contributing to the biophysical properties of lens fibre plasma membrane. Liquid chromatography followed by mass spectrometry was used to analyse bovine eye lens lipid membrane fractions after exposure to 5 and 50 Gy and eye lenses taken from wholebody 2 Gy-irradiated mice. Although cholesterol levels do not change significantly, IR dose-dependant formation of the oxysterols 7β-hydroxycholesterol, 7-ketocholesterol and 5, 6-epoxycholesterol in bovine lens nucleus membrane extracts was observed. Whole-body X-ray exposure (2 Gy) of 12-week old mice resulted in an increase in 7β-hydroxycholesterol and 7-ketocholesterol in their eye lenses. Their increase regressed over 24 h in the living lens cortex after IR exposure. This study also demonstrated that the IR-induced fold increase in oxysterols was greater in the mouse lens cortex than the nucleus. Further work is required to elucidate the mechanistic link(s) between oxysterols and IR-induced cataract, but these data evidence for the first time that IR exposure of mice results in oxysterol formation in their eye lenses.
摘要:
电离辐射(IR)是脂质过氧化的原因,和流行病学数据显示,暴露于IR与眼睛晶状体白内障的发展之间存在相关性。白内障仍然是全世界失明的主要原因。晶状体纤维细胞的质膜是人体内最富胆固醇的质膜之一,形成脂筏,并有助于晶状体纤维质膜的生物物理特性。在暴露于5和50Gy和取自全身2Gy照射的小鼠的眼晶状体后,使用液相色谱和质谱分析牛眼晶状体脂质膜部分。虽然胆固醇水平没有明显变化,氧固醇7β-羟基胆固醇的IR剂量依赖性形成,观察到牛晶状体核膜提取物中的7-酮胆固醇和5,6-环氧胆固醇。12周龄小鼠的全身X射线暴露(2Gy)导致其眼睛晶状体中7β-羟基胆固醇和7-酮胆固醇的增加。红外暴露后,它们在活晶状体皮层中的增加在24小时内消退。这项研究还表明,IR诱导的氧固醇倍数增加在小鼠晶状体皮质中比核更大。需要进一步的工作来阐明氧固醇和IR诱导的白内障之间的机制联系。但是这些数据首次证明,小鼠的IR暴露会导致眼晶状体中氧化固醇的形成。
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