{
  "abstract": "Purpose To develop a mesoporous silica nanoparticle-based delivery system for 4-phenylbutyric acid (4-PBA) and evaluate its potential to alleviate endoplasmic reticulum (ER) stress and improve mutant myocilin (MYOC)-associated glaucoma. Materials and methods We synthesized hollow/snowflake-like mesoporous silica nanoparticles loaded with 4-PBA (mSiO₂-PBA) for drug loading and release. Cellular uptake and cytotoxicity were evaluated in human corneal epithelial cells (HCECs) and human trabecular meshwork cells (HTMCs). The effects of mSiO₂-PBA on mutant MYOC secretion and ER stress-associated proteins were assessed by Western blot analysis. In Tg-MYOCN450Y mice, ocular distribution of mSiO₂-PBA was examined by fluorescence imaging and high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS). Therapeutic efficacy was evaluated by intraocular pressure (IOP) measurements, immunofluorescence analysis of MYOC accumulation and ER stress-associated markers in trabecular meshwork tissue, and transmission electron microscopy (TEM). Results mSiO₂-PBA exhibited efficient cellular uptake and favorable biocompatibility in vitro. Treatment with mSiO₂-PBA enhanced mutant MYOC secretion and reduced ER stress-associated KDEL-positive proteins in HTMCs. Following topical administration, mSiO₂-PBA achieved ocular penetration and exposure in trabecular meshwork tissue. In Tg-MYOCN450Y mice, mSiO₂-PBA significantly reduced IOP, decreased mutant MYOC accumulation, and improved ER ultrastructural abnormalities in trabecular meshwork cells. Conclusions mSiO₂-PBA represents a promising nanoparticle-based delivery platform for 4-PBA in MYOC-associated glaucoma. By promoting mutant MYOC secretion and alleviating ER stress, mSiO₂-PBA demonstrated therapeutic efficacy in vitro and in vivo, supporting its potential as a nanotherapeutic strategy for MYOC-associated glaucoma.",
  "abstract_shown": true,
  "affiliations": [
    "Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Key Laboratory of Intelligent Diagnosis Technology and Equipment for Optic Nerve-Related Eye Diseases, Capital Medical University",
    "State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology",
    "National Engineering Research Center for Rare Earth, Grirem Advanced Materials Co., Ltd."
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xuejing Yan"
    },
    {
      "affs": [
        1
      ],
      "name": "Wu Qin"
    },
    {
      "affs": [
        2
      ],
      "name": "Xiaoming Gan"
    },
    {
      "affs": [
        0
      ],
      "name": "Yingyan Mao"
    },
    {
      "affs": [
        0
      ],
      "name": "Shen Wu"
    },
    {
      "affs": [
        1
      ],
      "name": "Shipeng Wen"
    },
    {
      "affs": [
        0
      ],
      "name": "Jingxue Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5ean7jdke7na1.bib",
  "cited_by": 0,
  "doi": "10.1186/s13062-026-00907-z",
  "fulltext_url": "https://doi.org/10.1186/s13062-026-00907-z",
  "id": "5ean7jdke7na1",
  "issns": [
    "1745-6150"
  ],
  "landing_url": "https://doi.org/10.1186/s13062-026-00907-z",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QH301-705.5"
    ],
    [
      "openalex",
      "2731|Glaucoma and retinal disorders"
    ]
  ],
  "openalex": "W7169810362",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-07-01",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/5ean7jdke7na1.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:45:42Z",
      "native_id": "272d6457de504e88965ae6bd1168a3f5",
      "source": "doaj",
      "url": "https://doi.org/10.1186/s13062-026-00907-z"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Genomics and Phylogenetic Studies",
      "subfield": "molecular-biology"
    },
    {
      "field": "biology",
      "origin": "lcc:QH301-705.5",
      "subfield": "general"
    }
  ],
  "title": "4-phenylbutyric acid-loaded mesoporous silica nanoparticles alleviate endoplasmic reticulum stress and reduce intraocular pressure in glaucoma model",
  "title_text": "4-phenylbutyric acid-loaded mesoporous silica nanoparticles alleviate endoplasmic reticulum stress and reduce intraocular pressure in glaucoma model",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:45:42Z",
  "url": "https://research.draconitic.com/paper/5ean7jdke7na1",
  "venue": "Biology Direct",
  "versions": []
}