{
  "abstract": "Identifying factors that govern the ability of retinal ganglion cells (RGCs) to extend axons is an important step in developing therapies to achieve recovery after optic nerve injury. Here, we report that the intracellular domain of the leukemia inhibitory factor receptor (LIFR/CD118) is essential for mature RGCs’ ability to regenerate injured axons independent of the cognate ligand (LIF) and other therapies. Overexpression of LIFR in adult RGCs induces neurite outgrowth in cultured RGCs and axon regeneration in vivo while strongly amplifying RGCs’ response to LIF itself and to unrelated growth factors. Conversely, downregulation of LIFR strongly suppresses the pro-regenerative effects of PTEN knockdown and other potent stimuli. LIFR modulation alters the constitutive activity of the MAPK pathway, in contrast to LIF itself, which primarily activates pSTAT3. The extracellular domain–truncated LIFR construct retains substantial pro-regenerative activity, whereas mutation of intracellular signaling motifs reduces the full regenerative effect of LIFR. Together, these findings identify LIFR as a key cell-autonomous regulator of optic nerve regeneration in mature RGCs.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.",
    "Hunan Clinical Research Center of Ophthalmic Disease, Changsha, Hunan, China.",
    "Division of Rheumatology, Inflammation and Immunity, Brigham and Women’s Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.",
    "Departments of Neurosurgery and Ophthalmology, Boston Children’s Hospital and Harvard Medical School, Boston, Massachusetts, USA.",
    "Department of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Qian Jiang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Cong Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yuerong Ren"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Peiyun Duan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ke Tian"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiangwei Duan"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Binghan Cai"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Changzhong Xu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Ke Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Jian Li"
    },
    {
      "affs": [
        3
      ],
      "name": "Larry Benowitz",
      "orcid": "0000-0002-0277-7222"
    },
    {
      "affs": [
        4
      ],
      "name": "Ningli Wang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Bing Jiang"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Lili Xie"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/em0ghnqbnnk5a.bib",
  "cited_by": 0,
  "doi": "10.1172/jci.insight.202223",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13726422/",
  "id": "em0ghnqbnnk5a",
  "issns": [
    "2379-3708"
  ],
  "landing_url": "https://doi.org/10.1172/jci.insight.202223",
  "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",
      "Research Article"
    ],
    [
      "openalex",
      "2804|Nerve injury and regeneration"
    ]
  ],
  "openalex": "W7204896704",
  "pdf_url": "http://insight.jci.org/articles/view/202223/files/pdf",
  "pmcid": "PMC13726422",
  "pmid": "42678930",
  "published": "2026-09-01",
  "publisher": "American Society for Clinical Investigation",
  "ris": "https://research.draconitic.com/paper/em0ghnqbnnk5a.ris",
  "sources": [
    {
      "first_seen": "2026-11-05T12:22:47Z",
      "native_id": "PMC13726422",
      "source": "pmc",
      "url": "https://doi.org/10.1172/jci.insight.202223"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Nerve injury and regeneration",
      "subfield": "neuroscience"
    }
  ],
  "title": "Optic nerve regeneration requires the intracellular domain of LIFRα/CD118",
  "title_text": "Optic nerve regeneration requires the intracellular domain of LIFRα/CD118",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:22:47Z",
  "url": "https://research.draconitic.com/paper/em0ghnqbnnk5a",
  "venue": "JCI Insight",
  "versions": []
}