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Biochemistry of Eye Lens in the Norm and in Cataractogenesis

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Dedicated to Boris I. Kurganov

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.

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Abbreviations

AAR:

amino acid residue

ROS:

reactive oxygen species

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Funding

The study was supported by the Russian Science Foundation (project no. 21-14-00178 for K.O.M.) and Ministry of Science and Higher Education of the Russian Federation (Agreement no. 075-15-2020-795, intramural no. 13.1902.21.0027 for M.A.O.).

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Correspondence to Konstantin O. Muranov.

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The authors declare no conflicts of interest. The procedure for working with animals used to generate the data described in the complied with the ethics standards of facilities involved in investigation (Research Institute of Eye Diseases, Moscow, and Joint Institute for Nuclear Research, Dubna) and was approved by legislative acts of the Russian Federation and international organizations.

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Muranov, K.O., Ostrovsky, M.A. Biochemistry of Eye Lens in the Norm and in Cataractogenesis. Biochemistry Moscow 87, 106–120 (2022). https://doi.org/10.1134/S0006297922020031

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