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眼晶状体的正常生物化学和白内障发生的生物化学。

Biochemistry of Eye Lens in the Norm and in Cataractogenesis.

机构信息

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow, 119334, Russia.

出版信息

Biochemistry (Mosc). 2022 Feb;87(2):106-120. doi: 10.1134/S0006297922020031.

Abstract

The absence of cellular organelles in fiber cells and very high cytoplasmic protein concentration (up to 900 mg/ml) minimize light scattering in the lens and ensure its transparency. Low oxygen concentration, powerful defense systems (antioxidants, antioxidant enzymes, chaperone-like protein alpha-crystallin, etc.) maintain lens transparency. On the other hand, the ability of crystallins to accumulate age-associated post-translational modifications, which reduce the resistance of lens proteins to oxidative stress, is an important factor contributing to the cataract formation. Here, we suggest a mechanism of cataractogenesis common for the action of different cataractogenic factors, such as age, radiation, ultraviolet light, diabetes, etc. Exposure to these factors leads to the damage and death of lens epithelium, which allows oxygen to penetrate into the lens through the gaps in the epithelial layer and cause oxidative damage to crystallins, resulting in protein denaturation, aggregation, and formation of multilamellar bodies (the main cause of lens opacification). The review discusses various approaches to the inhibition of lens opacification (cataract development), in particular, a combined use of antioxidants and compounds enhancing the chaperone-like properties of alpha-crystallin. We also discuss the paradox of high efficiency of anti-cataract drugs in laboratory settings with the lack of their clinical effect, which might be due to the late use of the drugs at the stage, when the opacification has already formed. A probable solution to this situation will be development of new diagnostic methods that will allow to predict the emergence of cataract long before the manifestation of its clinical signs and to start early preventive treatment.

摘要

纤维细胞中没有细胞器,细胞质内蛋白质浓度非常高(高达 900mg/ml),这最大限度地减少了晶状体中的光散射,确保了其透明度。低氧浓度、强大的防御系统(抗氧化剂、抗氧化酶、伴侣样蛋白α-晶状体蛋白等)维持着晶状体的透明性。另一方面,晶状体蛋白能够积累与年龄相关的翻译后修饰,这降低了晶状体蛋白对氧化应激的抵抗力,是导致白内障形成的一个重要因素。在这里,我们提出了一种白内障形成的机制,该机制适用于不同白内障形成因素(如年龄、辐射、紫外线、糖尿病等)的共同作用。暴露于这些因素会导致晶状体上皮细胞受损和死亡,使氧气能够通过上皮层的间隙渗透到晶状体中,并对晶状体蛋白造成氧化损伤,导致蛋白质变性、聚集和形成多层体(晶状体混浊的主要原因)。本文讨论了抑制晶状体混浊(白内障发展)的各种方法,特别是联合使用抗氧化剂和增强α-晶状体蛋白伴侣样特性的化合物。我们还讨论了在实验室环境中抗白内障药物具有高效率而在临床应用中缺乏疗效的矛盾现象,这可能是由于在混浊已经形成的阶段才开始使用药物。解决这一问题的可能方法是开发新的诊断方法,这些方法可以在白内障临床症状出现之前很久就预测其发生,并尽早开始预防性治疗。

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