{
  "abstract": "Purpose: Subretinal fibrosis causes irreversible vision loss in neovascular age-related macular degeneration (nAMD) and remains poorly controlled by anti-vascular endothelial growth factor (VEGF) therapy. We investigated the role of B-crystallin (CRYAB) in angiogenic and fibrotic pathology and evaluated disease-associated CRYAB truncation as a therapeutic target. Methods: Aqueous humor from patients with nAMD was analyzed by quantitative proteomics and receiver operating characteristic (ROC) analysis. CRYAB function was assessed using knockout and knockdown approaches in a choroidal neovascularization (CNV) mouse model. CRYAB truncation and associated proteins were examined by immunoblotting, co-immunoprecipitation, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). C-terminal truncation was further examined in mouse retinal tissue using antibodies generated against full-length CRYAB and its C-terminal region. Primary human retinal pigment epithelial (hRPE)-THP-1 co-cultures were used to examine CRYAB truncation under fibrosis-associated conditions. Pharmacological effects were tested using ({+/-})-threo-3-methylglutamic acid (T3MG) and 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF). Results: CRYAB was upregulated in the aqueous humor of patients with nAMD. Higher CRYAB levels were associated with persistent lesions after initial anti-VEGF treatment. CRYAB knockout or knockdown reduced CNV pathology and decreased VEGFA and -smooth muscle actin (SMA) expression, without a significant substrain effect between C57BL/6N and C57BL/6J mice. A Ser45-phosphorylated truncated CRYAB species was detected in mouse laser-induced CNV model. We termed this species disease-associated truncated CRYAB in AMD (DTCAMD). Peptide mapping showed reproducible loss of distal C-terminal peptide coverage in truncated CRYAB. Consistent with this finding, C-terminal antibody recognition was reduced in CNV lesions. In hRPE-THP-1 co-cultures, DTCAMD accumulated with increased SMA expression. Proteomic analysis identified Prss1 as a candidate CRYAB-associated serine protease linked to truncation under CNV conditions. T3MG and AEBSF reduced DTCAMD-associated signals and CNV pathology. Conclusions: CRYAB contributes to angiogenic and fibrotic pathology in CNV. Disease-associated CRYAB truncation, particularly Ser45-phosphorylated DTCAMD, represents a potential therapeutic target for fibrotic remodeling in nAMD.",
  "abstract_shown": true,
  "affiliations": [
    "College of Pharmacy, Chungbuk National University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "name": "E. Yu"
    },
    {
      "name": "S. M. Gu"
    },
    {
      "name": "J. Jin"
    },
    {
      "name": "J. K. Min"
    },
    {
      "affs": [
        0
      ],
      "name": "J. Yun"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1gcrkrqjpb9e2.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.06.756917",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756917v1.full",
  "id": "1gcrkrqjpb9e2",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756917v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "pathology"
    ],
    [
      "openalex",
      "2731|Retinal Diseases and Treatments"
    ]
  ],
  "openalex": "W7221546390",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756917v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1gcrkrqjpb9e2.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:24Z",
      "native_id": "10.64898/2026.10.06.756917",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.06.756917v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pathology",
      "subfield": "general"
    }
  ],
  "title": "DTCAMD, a disease-associated truncated form of CRYAB in neovascular age-related macular degeneration: a potential driver of subretinal fibrosis",
  "title_text": "DTCAMD, a disease-associated truncated form of CRYAB in neovascular age-related macular degeneration: a potential driver of subretinal fibrosis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:24Z",
  "url": "https://research.draconitic.com/paper/1gcrkrqjpb9e2",
  "venue": "bioRxiv",
  "versions": []
}