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      Role of short-wavelength blue light in the formation of cataracts and the expression of caspase-1, caspase-11, Gasdermin D in rat lens epithelial cells: insights into a novel pathogenic mmechanism of cataracts

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          Abstract

          Background

          With the popularity of blue-rich light-emitting diode (LED)-backlit display devices, our eyes are now exposed to more short-wavelength blue light than they were in the past. The goal of this study was to investigate the pathogenesis of cataracts after short-wavelength light exposure.

          Methods

          Sprague-Dawley (SD) rats were selected and randomly divided into a control group (10 rats each for the 4-, 8-, and 12-week groups) and an experimental group (10 rats each for the 4-, 8-, and 12-week groups). The rats in the experimental group were exposed to a short-wavelength blue LED lamp for 12 h per day. After exposure to the blue LED lamp, the rats were maintained in total darkness for 12 h, after which a 12-h light/dark cycle was resumed. The intensity of the lamp was 3000 lx. At the end of the short-wavelength blue LED lamp exposure (for 4, 8, and 12 weeks), the expression levels of caspase-1, caspase-11 and gasdermin D (GSDMD) were examined in rat lens epithelial cells (LECs) using qRT-PCR and Western blot analyses. An illuminance of 2500 lx was used to study the potential effect of blue LED light on HLE-B3 hLECs in vitro . AC-YVAD-CMK, a caspase-1 inhibitor, was used to confirm the pyroptosis of LECs by flow cytometry.

          Results

          After 6 weeks, cataracts developed in the experimental rats (4/20 eyes). The clarity of the lens gradually worsened with the duration of exposure. Twelve weeks later, all of the rat eyes had developed cataracts. The expression levels of caspase-1, caspase-11 and GSDMD at 4, 8, and 12 weeks were significantly higher in the samples from rats exposed to a short-wavelength blue LED lamp than in the samples from control rats ( p<0.05). The proportions of double-positive hLECs were significantly increased in the 5-h and 10-h short-wavelength blue light exposure subgroups compared with the 5-h and 10-h caspase-1 inhibitor subgroups ( p < 0.05).

          Conclusion

          The data indicate that pyroptosis plays a key role in cataract induction after short-wavelength blue light exposure. This study might provide new insights into a novel pathogenic mechanism of cataracts.

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          Most cited references29

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          Recent Insights into the Molecular Mechanisms Underlying Pyroptosis and Gasdermin Family Functions.

          Pyroptosis is an inflammatory form of cell death that not only protects multicellular organisms from invading pathogenic bacteria and microbial infections, but can also lead to sepsis and lethal septic shock if overactivated. Here, we present an overview of recent developments within the pyroptosis field, beginning with the discovery of Gasdermin D (GSDMD) as a substrate of caspase-1 and caspase-11 upon detection of cytosolic lipopolysaccharide (LPS). Cleavage releases the N-terminal domain of GSDMD, causing it to form cytotoxic pores in the plasma membrane of cells. We further discuss the implications for the rest of the gasdermin (GSDM) family, which are emerging as mediators of programmed cell death in a variety of processes that regulate cellular differentiation and proliferation.
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            Number of People Blind or Visually Impaired by Cataract Worldwide and in World Regions, 1990 to 2010.

            To estimate prevalence and number of people visually impaired or blind due to cataract.
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              Cataract blindness--challenges for the 21st century.

              Cataract prevalence increases with age. As the world's population ages, cataract-induced visual dysfunction and blindness is on the increase. This is a significant global problem. The challenges are to prevent or delay cataract formation, and treat that which does occur. Genetic and environmental factors contribute to cataract formation. However, reducing ocular exposure to UV-B radiation and stopping smoking are the only interventions that can reduce factors that affect the risk of cataract. The cure for cataract is surgery, but this is not equally available to all, and the surgery which is available does not produce equal outcomes. Readily available surgical services capable of delivering good vision rehabilitation must be acceptable and accessible to all in need, no matter what their circumstances. To establish and sustain these services requires comprehensive strategies that go beyond a narrow focus on surgical technique. There must be changes in government priorities, population education, and an integrated approach to surgical and management training. This approach must include supply of start-up capital equipment, establishment of surgical audit, resupply of consumables, and cost-recovery mechanisms. Considerable innovation is required. Nowhere is this more evident than in the pursuit of secure funding for ongoing services.
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                Author and article information

                Contributors
                lzj6515@sina.com
                Journal
                BMC Ophthalmol
                BMC Ophthalmol
                BMC Ophthalmology
                BioMed Central (London )
                1471-2415
                15 July 2020
                15 July 2020
                2020
                : 20
                : 289
                Affiliations
                [1 ]GRID grid.410736.7, ISNI 0000 0001 2204 9268, Department of Ophthalmology, the First Affiliated Hospital, , Harbin Medical University, ; 143 Yiman Street, Nangang District, Harbin, China
                [2 ]Department of Ophthalmology, the 2nd Hospital of Heilongjiang, Harbin, China
                Author information
                http://orcid.org/0000-0003-0644-3497
                Article
                1565
                10.1186/s12886-020-01565-z
                7364504
                32669096
                37cee25f-fa21-4f34-8105-1196603b01e7
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 25 November 2019
                : 10 July 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81870643
                Award Recipient :
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2020

                Ophthalmology & Optometry
                pyroptosis,short-wavelength blue light,caspase-1/11,gsdmd,cataract
                Ophthalmology & Optometry
                pyroptosis, short-wavelength blue light, caspase-1/11, gsdmd, cataract

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