{
  "abstract": "Retinal fibrosis is a blinding complication of proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR), age-related macular degeneration (AMD) and idiopathic epiretinal membrane (iERM), yet effective therapies remain lacking. The purpose of this study was to investigate the role of BMP2 and BMP4 (BMP2/4)-activin receptor-like kinase (ALK) signaling in retinal fibrosis. BMP2 was detected in the vitreous of PDR, PVR, and rhegmatogenous retinal detachment (RRD) samples at concentration of 70, 180, and 85 pg/mL respectively, whereas it was present only at trace levels or was undetectable in the vitreous of macular hole and idiopathic ERM samples (~0.1 pg/mL). PDR, PVR, and idiopathic ERMs exhibited strong immunoreactivity for BMP2, BMP4, ALK3 (Bmpr1a), pSMAD1/5/9, and pSMAD4. Formation of preretinal fibronectin-containing membranes resulted from intravitreal injection of wild-type mice with BMP2 and similar membranes formed in mice expressing constitutively active ALK3 (caBmpr1a). The presence of preretinal membrane in caBmpr1a was confirmed by optical coherence tomography. The limited hyperoxia-induced proliferative retinopathy (LIHPR) model demonstrated a progressive increase in the retinal expression of BMP2 and BMP4and development of preretinal membrane. Administration of BMP/ALK inhibitor LDN193189 induced regression of the preretinal membrane in LHIPR. BMP2 and BMP4 induced a significant increase in the expression of Glial Fibrillary Acidic Protein (GFAP), fibronectin, and collagen-VI in cultured rat Muller glial cells, and increased fibronectin was reversed by BMP/ALK inhibition. BMP2 also significantly upregulated fibronectin and activated matrix metalloproteinase-2 in human retinal endothelial cells. These findings support BMP2/4-ALK signaling as a potential mediator and therapeutic target in retinal fibrosis.",
  "abstract_shown": true,
  "affiliations": [
    "Eye Research Centre, Oakland University William Beaumont School of Medicine, Rochester, MI 48309.",
    "Eye Research Institute, Oakland University, Rochester, MI 48309.",
    "Department of Ophthalmology, King Saud University, Riyadh 11461, Saudi Arabia.",
    "Center for Eye Research and Innovative Diagnostics, Department of Ophthalmology, Oslo University Hospital, Oslo 0450, Norway.",
    "Department of Ophthalmology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo 0450, Norway.",
    "Department of Ophthalmology, Faculty of Medicine, University of Split, Split 21000, Croatia.",
    "Univerzitet Kliment Ohridski Network, University St. Kliment Ohridski-Bitola, Bitola 7000, Macedonia.",
    "Department of Biologic and Materials Sciences and Prosthodontics, University of Michigan School of Dentistry, Ann Arbor, MI 48109.",
    "Department of Foundational Medical Studies, Oakland University William Beaumont-School of Medicine, Rochester, MI 48309."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Sonali Sharma",
      "orcid": "0009-0007-1009-3844"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Gieth Alahdab"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Muhammad Nazmul Haque"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ikbal Karkoukli",
      "orcid": "0009-0003-0933-3434"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Alee Assaf"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuichiro Ishida",
      "orcid": "0000-0002-6690-8463"
    },
    {
      "affs": [
        2
      ],
      "name": "Ahmed Abu Elasrar"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mohamed Moustafa"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mohamed Tarek",
      "orcid": "0009-0003-3259-4536"
    },
    {
      "affs": [
        1
      ],
      "name": "Xiao Zhang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Kenneth P Mitton"
    },
    {
      "affs": [
        3
      ],
      "name": "Natasha Josifovska"
    },
    {
      "affs": [
        3,
        4,
        5,
        6
      ],
      "name": "Goran Petrovski",
      "orcid": "0000-0003-2905-9252"
    },
    {
      "affs": [
        7
      ],
      "name": "Hiroki Ueharu"
    },
    {
      "affs": [
        7
      ],
      "name": "Yuji Mishina",
      "orcid": "0000-0002-6268-4204"
    },
    {
      "affs": [
        0,
        1,
        8
      ],
      "name": "Mohamed Al-Shabrawey",
      "orcid": "0000-0001-5362-7972"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/18z9355s9c406.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2603111123",
  "fulltext_url": "https://europepmc.org/articles/PMC13663773",
  "id": "18z9355s9c406",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://europepmc.org/article/MED/42842407",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2731|Retinal Diseases and Treatments"
    ]
  ],
  "openalex": "W7220864943",
  "pdf_url": "https://europepmc.org/articles/PMC13663773?pdf=render",
  "pmcid": "PMC13663773",
  "pmid": "42842407",
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/18z9355s9c406.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:02Z",
      "native_id": "MED:42842407",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42842407"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "journal-openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Bone morphogenetic protein signaling as a key regulator of retinal fibrosis.",
  "title_text": "Bone morphogenetic protein signaling as a key regulator of retinal fibrosis.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:02Z",
  "url": "https://research.draconitic.com/paper/18z9355s9c406",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}