{
  "abstract": "Purpose: The purpose of this study was to establish a long-term ex vivo mouse lens culture system and determine whether lipid peroxidation directly drives cataract-like changes in lens transparency, light scattering, stiffness, and crystallin biochemistry.\n\nMethods: Intact lenses from 3-month-old C57BL/6J mice were isolated and cultured in M199 for up to 2 weeks. Lipid peroxidation was induced by GPX4 inhibition (RAS-selective lethal 3 [RSL3]) or glutathione depletion (buthionine sulfoximine plus dimethyl fumarate [BSO+DMF]) and, where indicated, inhibited by liproxstatin-1 (Lip-1). Lens opacity was monitored by dark-field imaging. Visible absorbance spectra and a 440 to 650 nm scattering index were quantified using a custom 3D-printed cuvette mold. Lens stiffness was measured by MicroTester LT compression. Native membrane fractions were isolated by sucrose gradients for αA-crystallin immunoblotting, and protein aggregation was assessed by size-exclusion chromatography coupled with multi-angle light scattering (SEC-MALS).\n\nResults: Lenses remained transparent for at least 2 weeks in culture. RSL3 or BSO/DMF induced robust lipid peroxidation (4-hydroxynonenal [4-HNE]), progressive nuclear opacity, increased 440-nm absorbance and light scattering, and significantly elevated lens stiffness. Lip-1 markedly attenuated the absorbance/scattering changes. Lipid peroxidation increased αA-crystallin membrane association and promoted high-molecular-weight protein aggregate formation.\n\nConclusions: This ex vivo organ-culture model provides direct evidence that lipid peroxidation is sufficient to induce cataract-relevant lens stiffening and opacification, accompanied by crystallin–membrane association and protein aggregation. These findings establish lipid peroxidation as a key contributor to cataract-associated optical, mechanical, and biochemical changes.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University, Augusta, Georgia, United States",
    "Division of Biological Sciences, Franklin College of Arts and Sciences, University of Georgia, Athens, Georgia, United States"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Emily Fan"
    },
    {
      "affs": [
        0
      ],
      "name": "Caili Hao"
    },
    {
      "affs": [
        0
      ],
      "name": "Shuyu Zheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Ming Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Xingjun Fan"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5tvn6mtaa4smd.bib",
  "cited_by": 0,
  "doi": "10.1167/iovs.67.12.67",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13722986/",
  "id": "5tvn6mtaa4smd",
  "issns": [
    "0146-0404",
    "1552-5783"
  ],
  "landing_url": "https://doi.org/10.1167/iovs.67.12.67",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Lens"
    ],
    [
      "openalex",
      "1312|Connexins and lens biology"
    ]
  ],
  "openalex": "W7224003652",
  "pdf_url": null,
  "pmcid": "PMC13722986",
  "pmid": "42937439",
  "published": "2026-10-27",
  "publisher": "Association for Research in Vision and Ophthalmology",
  "ris": "https://research.draconitic.com/paper/5tvn6mtaa4smd.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:21:41Z",
      "native_id": "PMC13722986",
      "source": "pmc",
      "url": "https://doi.org/10.1167/iovs.67.12.67"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Connexins and lens biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Lipid Peroxidation Increases Lens Stiffness and Is Associated With αA-Crystallin Accumulation at the Plasma Membrane: An Ex Vivo Study",
  "title_text": "Lipid Peroxidation Increases Lens Stiffness and Is Associated With αA-Crystallin Accumulation at the Plasma Membrane: An Ex Vivo Study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:21:41Z",
  "url": "https://research.draconitic.com/paper/5tvn6mtaa4smd",
  "venue": "Investigative Ophthalmology & Visual Science",
  "versions": []
}