{
  "abstract": "Dry age-related macular degeneration (AMD) is initiated by retinal pigment epithelium (RPE) dysfunction, yet early metabolic mechanisms linking RPE injury to photoreceptor dysfunction remain unclear. Using a physiologically relevant mouse model, we performed cell-type–resolved lipidomic and transcriptomic profiling with ultrastructural analyses. RPE-specific loss of Chloride Intracellular Channel 4 (CLIC4) induced coordinated lipid remodeling and transcriptional rewiring compromising RPE–photoreceptor lipid homeostasis. Both RPE and neural retina exhibited shifts toward very-long-chain unsaturated phospholipids and ceramides, while mutant RPE also accumulated saturated very-long-chain ceramides and cholesterol, particularly in females, favoring drusen deposition. Strikingly, RPE and rods mounted divergent responses: RPE activated compensatory mechanisms, whereas rods exhibited transcriptomic and ultrastructural evidence of bioenergetic suppression, mitochondrial structural abnormalities, and mitochondria-derived oxidative damage, establishing a feed-forward stress cycle extending beyond canonical rod-RPE carbon-energy coupling. These findings underscore rod mitochondrial structural integrity as a potential early biomarker, positioning disrupted lipid recycling as a targetable axis in dry AMD pathogenesis.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology, Margaret M. Dyson Vision Research Institute, Weill Cornell Medicine, New York, NY USA",
    "Neuroscience Center of Excellence, School of Medicine, Louisiana State University Health Sciences Center, New Orleans, LA USA",
    "The Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD USA",
    "Department of Radiology, Weill Cornell Medicine, Brain Health Imaging Institute, New York, NY USA",
    "Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, NY USA"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Neeta Roy"
    },
    {
      "affs": [
        0
      ],
      "name": "Jen-Zen Chuang"
    },
    {
      "affs": [
        0
      ],
      "name": "Ting-Huan Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ye Sun"
    },
    {
      "affs": [
        1
      ],
      "name": "Danielle E. Allen",
      "orcid": "0009-0005-0833-1490"
    },
    {
      "affs": [
        1
      ],
      "name": "Marie-Audrey I. Kautzmann",
      "orcid": "0000-0001-7641-8743"
    },
    {
      "affs": [
        1
      ],
      "name": "Surjyadipta Bhattacharjee",
      "orcid": "0000-0003-0185-553X"
    },
    {
      "affs": [
        2
      ],
      "name": "Maxwell Ping Lee"
    },
    {
      "affs": [
        3
      ],
      "name": "Laura Beth J. McIntire"
    },
    {
      "affs": [
        1
      ],
      "name": "Nicolas G. Bazan",
      "orcid": "0000-0002-9243-5444"
    },
    {
      "affs": [
        0,
        4
      ],
      "name": "Ching-Hwa Sung",
      "orcid": "0000-0002-3468-5867"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/066crg73z5t2j.bib",
  "cited_by": 0,
  "doi": "10.1038/s41419-026-09147-5",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13736989/",
  "id": "066crg73z5t2j",
  "issns": [
    "2041-4889"
  ],
  "landing_url": "https://doi.org/10.1038/s41419-026-09147-5",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2731|Retinal Diseases and Treatments"
    ]
  ],
  "openalex": "W7196952721",
  "pdf_url": null,
  "pmcid": "PMC13736989",
  "pmid": "42982791",
  "published": "2026-08-07",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/066crg73z5t2j.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:18Z",
      "native_id": "PMC13736989",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41419-026-09147-5"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2731|Retinal Diseases and Treatments",
      "subfield": "general"
    }
  ],
  "title": "Lipidomic and transcriptomic remodeling underlies early retinal pathogenesis in dry age-related macular degeneration",
  "title_text": "Lipidomic and transcriptomic remodeling underlies early retinal pathogenesis in dry age-related macular degeneration",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:18Z",
  "url": "https://research.draconitic.com/paper/066crg73z5t2j",
  "venue": "Cell Death & Disease",
  "versions": []
}