{
  "abstract": "In mammals, retinal ganglion cells (RGCs) show very minor axonal regeneration following axotomy. Despite genetic and pharmacological efforts to promote this regeneration, progress remains slow and limited, especially in overcoming potentially cell-type-specific barriers. In this paper, we virally expressed melanopsin (OPN4), which is the native photopigment in intrinsically-photosensitive RGCs (ipRGCs), broadly in RGCs. IpRGCs are known to show relative resistance to degeneration and axonal loss after injury. We correlated the exogenous-melanopsin-mediated intrinsic light responses of the successfully infected RGCs (referred to as +OPN4RGCs) with their ability to show axonal regeneration after an optic-nerve crush. Specifically, we found +OPN4RGCs to show functional rhabdomeric and ciliary motifs of phototransduction as we previously found in ipRGCs. +OPN4αRGCs (the largest RGCs in the retina) exhibited light-triggered fast (via TRPC signaling) and slow (via cAMP signaling) response components, whereas +OPN4non-αRGC responses comprised predominantly just a fast component. Genetic ablation of TRPC channels (TRPC6/7) or group II adenylyl cyclase (AC2/4/7) to abolish the fast or the slow response component, respectively, largely attenuated the axonal regeneration of +OPN4αRGCs in the optic-nerve-crush model. At the same time, administration of cell-permeant cAMP not only rescued the AC2/4/7-knock-out phenotype in +OPN4αRGCs but also potentiated axonal regeneration in some +OPN4non-αRGCs, thus, possibly overcoming the potential subtype-specific barrier to axonal regeneration. Our results reveal an important role of joint TRPC- and cAMP-signaling in +OPN4RGC axonal regeneration.",
  "abstract_shown": true,
  "affiliations": [
    "Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205",
    "Retina Section, Department of Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 201318, China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Guang Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Zuying Chai",
      "orcid": "0000-0003-1449-9351"
    },
    {
      "affs": [
        0
      ],
      "name": "Sonya Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Yanxi Ren"
    },
    {
      "affs": [
        0
      ],
      "name": "King-Wai Yau"
    },
    {
      "affs": [
        0
      ],
      "name": "Sihan Li"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1br6yr9nwx5dx.bib",
  "cited_by": 0,
  "doi": "10.1073/pnas.2628062123",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732045/",
  "id": "1br6yr9nwx5dx",
  "issns": [
    "0027-8424",
    "1091-6490"
  ],
  "landing_url": "https://doi.org/10.1073/pnas.2628062123",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "412"
    ],
    [
      "heading",
      "Biological Sciences"
    ],
    [
      "heading",
      "Developmental Biology"
    ],
    [
      "openalex",
      "2804|Nerve injury and regeneration"
    ]
  ],
  "openalex": "W7223903149",
  "pdf_url": null,
  "pmcid": "PMC13732045",
  "pmid": "42945256",
  "published": "2026-10-27",
  "publisher": "National Academy of Sciences",
  "ris": "https://research.draconitic.com/paper/1br6yr9nwx5dx.ris",
  "sources": [
    {
      "first_seen": "2026-11-08T12:22:06Z",
      "native_id": "PMC13732045",
      "source": "pmc",
      "url": "https://doi.org/10.1073/pnas.2628062123"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "heading:Developmental Biology",
      "subfield": "developmental-biology"
    }
  ],
  "title": "Ectopic expression of melanopsin promotes axonal regeneration in retinal ganglion cells via cAMP and TRPC signaling",
  "title_text": "Ectopic expression of melanopsin promotes axonal regeneration in retinal ganglion cells via cAMP and TRPC signaling",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:06Z",
  "url": "https://research.draconitic.com/paper/1br6yr9nwx5dx",
  "venue": "Proceedings of the National Academy of Sciences of the United States of America",
  "versions": []
}