{
  "abstract": "Purpose. Trabecular meshwork (TM) dysfunction contributes to the elevated intraocular pressure in primary open-angle glaucoma. To better understand the molecular signature distinguishing glaucomatous from normal TM cells, we interrogated their genome-wide transcriptomic differences in a tissue-like soft extracellular matrix (ECM) microenvironment. Methods. Primary human glaucomatous and normal TM cell strains (N = 5 each) from three independent laboratories were plated on bioengineered collagen type I/hyaluronic acid/elastin-like polypeptide ECM hydrogels in 10% FBS media for 4-5 days, then serum-free media for 2 days. Cell-laden hydrogels were homogenized in TRIzol for RNA isolation, quality assessment, and library preparation, followed by paired-end 100-bp Illumina sequencing. Differential expression was assessed using DESeq2, including glaucoma status, originating laboratory, and donor age/sex in the model. Differentially expressed genes (DEGs) were defined as p < 0.05 and |fold change| [≥] 2, followed by Gene Ontology (GO) enrichment and QIAGEN Ingenuity Pathway Analysis (IPA). Results. In total, 588 DEGs distinguished the glaucomatous from the normal TM transcriptome (393 up-regulated in glaucomatous TM; 195 up-regulated in normal TM, i.e., down-regulated in glaucomatous TM). GO and IPA causal analyses revealed three coordinated disease programs: (i) TGF-{beta}/Wnt-driven ECM remodeling and fibrosis, (ii) NF-{kappa}B-associated inflammation, and (iii) a hypoxia/metabolic-stress program linked to p300/CREBBP chromatin co-activation. Conclusions. These data define a transcriptomic signature of glaucomatous TM cells when cultured in a soft physiologic ECM microenvironment, independent of the originating laboratory, with three mechanistic axes (ECM/fibrosis, inflammation, hypoxia/metabolism), and nominate p300 (encoded by EP300) as a candidate upstream node integrating these programs.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology and Visual Sciences, Center for Vision Research, SUNY Upstate Medical University, Syracuse, NY 13210, USA",
    "Department of Biochemistry and Molecular Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA",
    "Department of Cellular Biology and Anatomy, Augusta University, Augusta, GA 30912, USA",
    "Department of Neuroscience, SUNY Upstate Medical University, Syracuse, NY 13210, USA",
    "Department of Ophthalmology, Duke Eye Center, Duke University, Durham, NC 27705, USA",
    "Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA",
    "Department of Ophthalmology, Mayo Clinic, Rochester, MN 55905, USA",
    "Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA",
    "BioInspired Institute, Syracuse University, Syracuse, NY 13244, USA",
    "Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, NY 13244, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Rajanya Ghosh",
      "orcid": "0000-0001-7694-0574"
    },
    {
      "affs": [
        2
      ],
      "name": "Rachel Hadvina"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Ana N. Strat",
      "orcid": "0000-0001-6499-1518"
    },
    {
      "affs": [
        0,
        3
      ],
      "name": "Preethi S. Ganapathy",
      "orcid": "0000-0001-5736-7485"
    },
    {
      "affs": [
        4
      ],
      "name": "W. Daniel Stamer",
      "orcid": "0000-0002-2504-8997"
    },
    {
      "affs": [
        5
      ],
      "name": "Kate E. Keller",
      "orcid": "0000-0002-1616-972X"
    },
    {
      "affs": [
        2,
        6
      ],
      "name": "Yutao Liu",
      "orcid": "0000-0003-2870-4504"
    },
    {
      "affs": [
        0,
        1,
        7,
        8,
        9
      ],
      "name": "Samuel Herberg",
      "orcid": "0000-0001-7196-2010"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1nw08ngea8q17.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.26.761819",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761819v1.full",
  "id": "1nw08ngea8q17",
  "issns": [
    "2692-8205"
  ],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761819v1",
  "language": "en",
  "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",
      "cell biology"
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    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2731|Glaucoma and retinal disorders"
    ]
  ],
  "openalex": "W7224106016",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761819v1.full.pdf",
  "pmcid": "PMC13715897",
  "pmid": "42959075",
  "published": "2026-10-26",
  "publisher": "Cold Spring Harbor Laboratory Preprints",
  "ris": "https://research.draconitic.com/paper/1nw08ngea8q17.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:30:00Z",
      "native_id": "10.64898/2026.10.26.761819",
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      "url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761819v1"
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    {
      "first_seen": "2026-11-01T12:23:05Z",
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  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Transcriptomic profiling of normal and glaucomatous trabecular meshwork cells in a tissue-like soft ECM environment",
  "title_text": "Transcriptomic profiling of normal and glaucomatous trabecular meshwork cells in a tissue-like soft ECM environment",
  "type": "preprint",
  "updated_at": "2026-11-01T12:23:05Z",
  "url": "https://research.draconitic.com/paper/1nw08ngea8q17",
  "venue": "bioRxiv",
  "versions": []
}