{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T15:30:45Z","timestamp":1776353445124,"version":"3.51.2"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T00:00:00Z","timestamp":1742342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["JP 23K15945"],"award-info":[{"award-number":["JP 23K15945"]}]},{"name":"JSPS KAKENHI","award":["S2022-2"],"award-info":[{"award-number":["S2022-2"]}]},{"DOI":"10.13039\/501100004043","name":"Kanazawa Medical University","doi-asserted-by":"publisher","award":["JP 23K15945"],"award-info":[{"award-number":["JP 23K15945"]}],"id":[{"id":"10.13039\/501100004043","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004043","name":"Kanazawa Medical University","doi-asserted-by":"publisher","award":["S2022-2"],"award-info":[{"award-number":["S2022-2"]}],"id":[{"id":"10.13039\/501100004043","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Cataracts, the leading cause of blindness globally, are caused by oxidative stress and inflammation, which disrupt lens transparency due to increased accumulation of reactive oxygen species (ROS) as well as protein and DNA damage during aging. Using in vitro, ex vivo, and in vivo models, we determined the protective efficacy of N-acetylcysteine amide (NACA) against oxidative stress-induced and aging-induced cataractogenesis. We found that lens epithelial cells exposed to the oxidative stress inducers hydrogen peroxide (H2O2) or tert-butyl hydroperoxide showed significant ROS accumulation and reduced cellular viability. These effects were inhibited by NACA via the suppression of ROS and thioredoxin-interacting protein (Txnip) expression, a regulator of oxidative stress-related cellular damage and inflammation. In ex vivo lens experiments, NACA significantly reduced H2O2-induced lens opacity and preserved lens integrity. Similarly to NACA-treated lenses ex vivo, the integrity and opacity of aged mouse lenses, when topically instilled with NACA, were preserved and reduced, respectively, and are directly related to reduced Txnip and increased thioredoxin (Trx) expression levels. Overall, our findings demonstrated the protective ability of NACA to abate aberrant redox-active pathways, particularly the ROS\/TRX\/TXNIP axis, thereby preventing cataractogenesis and preserving eye lens integrity and ultimately impeding aging-related cataracts.<\/jats:p>","DOI":"10.3390\/biom15030442","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T10:38:48Z","timestamp":1742380728000},"page":"442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Topical Instillation of N-Acetylcysteine and N-Acetylcysteine Amide Impedes Age-Related Lens Opacity in Mice"],"prefix":"10.3390","volume":"15","author":[{"given":"Hidetoshi","family":"Ishida","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Kanazawa Medical University, Kanazawa 9200293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kanazawa Medical University, Kanazawa 9200293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teppei","family":"Shibata","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kanazawa Medical University, Kanazawa 9200293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6458-5330","authenticated-orcid":false,"given":"Hiroshi","family":"Sasaki","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kanazawa Medical University, Kanazawa 9200293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-8765","authenticated-orcid":false,"given":"Bhavana","family":"Chhunchha","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dhirendra P.","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6789-9311","authenticated-orcid":false,"given":"Eri","family":"Kubo","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kanazawa Medical University, Kanazawa 9200293, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e339","DOI":"10.1016\/S2214-109X(13)70113-X","article-title":"Causes of vision loss worldwide, 1990\u20132010: A systematic analysis","volume":"1","author":"Bourne","year":"2013","journal-title":"Lancet Glob. 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