{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:08:19Z","timestamp":1790744899167,"version":"4.1.0"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T00:00:00Z","timestamp":1709510400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000053","name":"U.S. Department of Health & Human Services | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["EY003790"],"award-info":[{"award-number":["EY003790"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Calcitonin gene-related peptide (CGRP) is a multifunctional neuropeptide abundantly expressed by corneal nerves. Using a murine model of corneal mechanical injury, we found CGRP levels in the cornea significantly reduced after injury. Topical application of CGRP as an eye drop accelerates corneal epithelial wound closure, reduces corneal opacification, and prevents corneal edema after injury in vivo. CGRP promotes corneal epithelial cell migration, proliferation, and the secretion of laminin. It reduces TGF-\u03b21 signaling and prevents TGF-\u03b21-mediated stromal fibroblast activation and tissue fibrosis. CGRP preserves corneal endothelial cell density, morphology, and pump function, thus reducing corneal edema. Lastly, CGRP reduces neutrophil infiltration, macrophage maturation, and the production of inflammatory cytokines in the cornea. Taken together, our results show that corneal nerve-derived CGRP plays a cytoprotective, pro-regenerative, anti-fibrotic, and anti-inflammatory role in corneal wound healing. In addition, our results highlight the critical role of sensory nerves in ocular surface homeostasis and injury repair.<\/jats:p>","DOI":"10.1038\/s42003-024-05934-y","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T07:02:47Z","timestamp":1709535767000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Topical application of calcitonin gene-related peptide as a regenerative, antifibrotic, and immunomodulatory therapy for corneal injury"],"prefix":"10.1038","volume":"7","author":[{"given":"Asmaa A.","family":"Zidan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsayed","family":"Elbasiony","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheyda","family":"Najafi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhirong","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rohan Bir","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirreza","family":"Naderi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1340-6758","authenticated-orcid":false,"given":"Jia","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,4]]},"reference":[{"key":"5934_CR1","doi-asserted-by":"publisher","unstructured":"Wang, E. et al. Global trends in blindness and vision impairment due to corneal opacity 1984-2020: a meta-analysis. Ophthalmology https:\/\/doi.org\/10.1016\/j.ophtha.2023.03.012 (2023).","DOI":"10.1016\/j.ophtha.2023.03.012"},{"key":"5934_CR2","doi-asserted-by":"publisher","first-page":"813","DOI":"10.1016\/j.ophtha.2020.06.042","volume":"128","author":"BH Jeng","year":"2021","unstructured":"Jeng, B. H. & Ahmad, S. In pursuit of the elimination of corneal blindness: is establishing eye banks and training surgeons enough? Ophthalmology 128, 813\u2013815 (2021).","journal-title":"Ophthalmology"},{"key":"5934_CR3","doi-asserted-by":"publisher","first-page":"33","DOI":"10.2165\/00002018-200225010-00004","volume":"25","author":"CN McGhee","year":"2002","unstructured":"McGhee, C. N., Dean, S. & Danesh-Meyer, H. Locally administered ocular corticosteroids: benefits and risks. Drug Safety 25, 33\u201355 (2002).","journal-title":"Drug Safety"},{"key":"5934_CR4","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1001\/jamaophthalmol.2015.4776","volume":"134","author":"P Gain","year":"2016","unstructured":"Gain, P. et al. Global survey of corneal transplantation and eye banking. JAMA Ophthalmol. 134, 167\u2013173, (2016).","journal-title":"JAMA Ophthalmol."},{"key":"5934_CR5","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1016\/S0140-6736(12)60437-1","volume":"379","author":"DT Tan","year":"2012","unstructured":"Tan, D. T., Dart, J. K., Holland, E. J. & Kinoshita, S. Corneal transplantation. Lancet 379, 1749\u20131761 (2012).","journal-title":"Lancet"},{"key":"5934_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107704","volume":"186","author":"E Lorenzo-Mart\u00edn","year":"2019","unstructured":"Lorenzo-Mart\u00edn, E. et al. Dynamic changes of the extracellular matrix during corneal wound healing. Exp. Eye Res. 186, 107704 (2019).","journal-title":"Exp. Eye Res."},{"key":"5934_CR7","doi-asserted-by":"publisher","first-page":"108089","DOI":"10.1016\/j.exer.2020.108089","volume":"197","author":"SE Wilson","year":"2020","unstructured":"Wilson, S. E. Corneal wound healing. Exp. Eye Res. 197, 108089 (2020).","journal-title":"Exp. Eye Res."},{"key":"5934_CR8","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/S1350-9462(01)00008-8","volume":"20","author":"SE Wilson","year":"2001","unstructured":"Wilson, S. E. et al. The corneal wound healing response: cytokine-mediated interaction of the epithelium, stroma, and inflammatory cells. Prog. Retin. Eye Res. 20, 625\u2013637 (2001).","journal-title":"Prog. Retin. Eye Res."},{"key":"5934_CR9","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1016\/j.jtos.2020.10.006","volume":"19","author":"S Kamil","year":"2021","unstructured":"Kamil, S. & Mohan, R. R. Corneal stromal wound healing: major regulators and therapeutic targets. Ocul. Surf. 19, 290\u2013306 (2021).","journal-title":"Ocul. Surf."},{"key":"5934_CR10","doi-asserted-by":"publisher","first-page":"3964","DOI":"10.1167\/iovs.04-0439","volume":"45","author":"P Sagoo","year":"2004","unstructured":"Sagoo, P., Chan, G., Larkin, D. F. P. & George, A. J. T. Inflammatory cytokines induce apoptosis of corneal endothelium through nitric oxide. Invest. Ophthalmol. Vis. Sci. 45, 3964\u20133973, (2004).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR11","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1002\/jcp.25623","volume":"232","author":"L Mastropasqua","year":"2017","unstructured":"Mastropasqua, L., Massaro\u2010Giordano, G., Nubile, M. & Sacchetti, M. Understanding the pathogenesis of neurotrophic keratitis: the role of corneal nerves. J. Cell. Physiol. 232, 717\u2013724 (2017).","journal-title":"J. Cell. Physiol."},{"key":"5934_CR12","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.survophthal.2013.09.002","volume":"59","author":"BS Shaheen","year":"2014","unstructured":"Shaheen, B. S., Bakir, M. & Jain, S. Corneal nerves in health and disease. Surv. Ophthalmol. 59, 263\u2013285 (2014).","journal-title":"Surv. Ophthalmol."},{"key":"5934_CR13","doi-asserted-by":"publisher","first-page":"101105","DOI":"10.1016\/j.preteyeres.2022.101105","volume":"91","author":"M Wu","year":"2022","unstructured":"Wu, M., Hill, L. J., Downie, L. E. & Chinnery, H. R. Neuroimmune crosstalk in the cornea: the role of immune cells in corneal nerve maintenance during homeostasis and inflammation. Prog. Retin. Eye Res. 91, 101105 (2022).","journal-title":"Prog. Retin. Eye Res."},{"key":"5934_CR14","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1006\/exer.1994.1145","volume":"59","author":"J Garcia-Hirschfeld","year":"1994","unstructured":"Garcia-Hirschfeld, J., Lopez-Briones, L. G. & Belmonte, C. Neurotrophic influences on corneal epithelial cells. Exp. Eye Res. 59, 597\u2013605 (1994).","journal-title":"Exp. Eye Res."},{"key":"5934_CR15","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41374-018-0118-4","volume":"99","author":"Y Okada","year":"2019","unstructured":"Okada, Y. et al. Sensory nerve supports epithelial stem cell function in healing of corneal epithelium in mice: the role of trigeminal nerve transient receptor potential vanilloid 4. Lab. Invest. 99, 210\u2013230 (2019).","journal-title":"Lab. Invest."},{"key":"5934_CR16","doi-asserted-by":"publisher","first-page":"101039","DOI":"10.1016\/j.preteyeres.2021.101039","volume":"89","author":"F-SX Yu","year":"2022","unstructured":"Yu, F.-S. X. et al. The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas. Prog. Ret. Eye Res. 89, 101039 (2022).","journal-title":"Prog. Ret. Eye Res."},{"key":"5934_CR17","doi-asserted-by":"publisher","unstructured":"Puri, S., Kenyon, B. M. & Hamrah, P. Immunomodulatory role of neuropeptides in the cornea. Biomedicines https:\/\/doi.org\/10.3390\/biomedicines10081985 (2022).","DOI":"10.3390\/biomedicines10081985"},{"key":"5934_CR18","doi-asserted-by":"publisher","first-page":"109125","DOI":"10.1016\/j.exer.2022.109125","volume":"220","author":"S Zhu","year":"2022","unstructured":"Zhu, S. et al. Promotion of corneal angiogenesis by sensory neuron-derived calcitonin gene-related peptide. Exp. Eye Res. 220, 109125 (2022).","journal-title":"Exp. Eye Res."},{"key":"5934_CR19","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1097\/j.pain.0000000000000831","volume":"158","author":"S Iyengar","year":"2017","unstructured":"Iyengar, S., Ossipov, M. H. & Johnson, K. W. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine. Pain 158, 543\u2013559 (2017).","journal-title":"Pain"},{"key":"5934_CR20","doi-asserted-by":"publisher","unstructured":"Deganutti, G. et al. Exploring ligand binding to calcitonin gene-related peptide receptors. Front. Mol. Biosci. https:\/\/doi.org\/10.3389\/fmolb.2021.720561 (2021).","DOI":"10.3389\/fmolb.2021.720561"},{"key":"5934_CR21","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/S0149-7634(96)00023-1","volume":"21","author":"D Van Rossum","year":"1997","unstructured":"Van Rossum, D., Hanisch, U.-K. & Quirion, R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci. Biobehav. Rev. 21, 649\u2013678 (1997).","journal-title":"Neurosci. Biobehav. Rev."},{"key":"5934_CR22","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1111\/head.12179","volume":"53","author":"ME Bigal","year":"2013","unstructured":"Bigal, M. E., Walter, S. & Rapoport, A. M. Calcitonin gene-related peptide (CGRP) and migraine current understanding and state of development. Headache 53, 1230\u20131244 (2013).","journal-title":"Headache"},{"key":"5934_CR23","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.regpep.2013.03.020","volume":"184","author":"Y Zhou","year":"2013","unstructured":"Zhou, Y. et al. Calcitonin gene-related peptide promotes the wound healing of human bronchial epithelial cells via PKC and MAPK pathways. Regul. Pept. 184, 22\u201329 (2013).","journal-title":"Regul. Pept."},{"key":"5934_CR24","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1016\/j.biopha.2008.02.003","volume":"62","author":"M Toda","year":"2008","unstructured":"Toda, M. et al. Roles of calcitonin gene-related peptide in facilitation of wound healing and angiogenesis. Biomed. Pharmacother. 62, 352\u2013359 (2008).","journal-title":"Biomed. Pharmacother."},{"key":"5934_CR25","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.2337\/db19-0870","volume":"69","author":"Y Zhang","year":"2020","unstructured":"Zhang, Y. et al. Role of VIP and sonic hedgehog signaling pathways in mediating epithelial wound healing, sensory nerve regeneration, and their defects in diabetic corneas. Diabetes 69, 1549\u20131561 (2020).","journal-title":"Diabetes"},{"key":"5934_CR26","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/j.immuni.2019.06.009","volume":"51","author":"H Nagashima","year":"2019","unstructured":"Nagashima, H. et al. Neuropeptide CGRP limits group 2 innate lymphoid cell responses and constrains type 2 inflammation. Immunity 51, 682\u2013695.e686 (2019).","journal-title":"Immunity"},{"key":"5934_CR27","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.jhep.2009.03.022","volume":"51","author":"I Kroeger","year":"2009","unstructured":"Kroeger, I. et al. The neuropeptide calcitonin gene-related peptide (CGRP) prevents inflammatory liver injury in mice. J. Hepatol. 51, 342\u2013353 (2009).","journal-title":"J. Hepatol."},{"key":"5934_CR28","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1097\/01.shk.0000183395.29014.7c","volume":"24","author":"RN Gomes","year":"2005","unstructured":"Gomes, R. N. et al. Calcitonin gene-related peptide inhibits local acute inflammation and protects mice against lethal endotoxemia. Shock 24, 590\u2013594 (2005).","journal-title":"Shock"},{"key":"5934_CR29","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/S1094-5539(03)00049-X","volume":"16","author":"J Springer","year":"2003","unstructured":"Springer, J., Geppetti, P., Fischer, A. & Groneberg, D. A. Calcitonin gene-related peptide as inflammatory mediator. Pulm. Pharmacol. Ther. 16, 121\u2013130 (2003).","journal-title":"Pulm. Pharmacol. Ther."},{"key":"5934_CR30","doi-asserted-by":"publisher","first-page":"100361","DOI":"10.1016\/j.bbih.2021.100361","volume":"18","author":"YJ Kim","year":"2021","unstructured":"Kim, Y. J. & Granstein, R. D. Roles of calcitonin gene-related peptide in the skin, and other physiological and pathophysiological functions. Brain Behav. Immun. Health 18, 100361 (2021).","journal-title":"Brain Behav. Immun. Health"},{"key":"5934_CR31","first-page":"3124","volume":"64","author":"A Zidan","year":"2023","unstructured":"Zidan, A. et al. Anti-inflammatory and anti-fibrotic effects of calcitonin gene-related peptide on corneal wound healing. Invest. Ophthalmol. Vis. Sci. 64, 3124\u20133124 (2023).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR32","doi-asserted-by":"publisher","first-page":"126","DOI":"10.3928\/1081-597X-19950301-13","volume":"11","author":"TM Tervo","year":"1995","unstructured":"Tervo, T. M. et al. Release of calcitonin gene-related peptide in tears after excimer laser photorefractive keratectomy. J. Refract. Surg. 11, 126\u2013128 (1995).","journal-title":"J. Refract. Surg."},{"key":"5934_CR33","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1016\/S0014-4835(05)80007-7","volume":"60","author":"P Mertaniemi","year":"1995","unstructured":"Mertaniemi, P., Yl\u00e4tupa, S., Partanen, P. & Tervo, T. Increased release of immunoreactive calcitonin gene-related peptide (CGRP) in tears after excimer laser keratectomy. Exp. Eye Res. 60, 659\u2013665 (1995).","journal-title":"Exp. Eye Res."},{"key":"5934_CR34","doi-asserted-by":"crossref","unstructured":"Mikulec, A. A. & Tanelian, D. L. CGRP increases the rate of corneal re-epithelialization in an in vitro whole mount preparation. J. Ocul. Pharmacol. Ther. 12, 417\u2013423 (1996).","DOI":"10.1089\/jop.1996.12.417"},{"key":"5934_CR35","doi-asserted-by":"publisher","first-page":"108002","DOI":"10.1016\/j.exer.2020.108002","volume":"194","author":"SE Wilson","year":"2020","unstructured":"Wilson, S. E., Torricelli, A. A. M. & Marino, G. K. Corneal epithelial basement membrane: Structure, function and regeneration. Exp. Eye Res. 194, 108002 (2020).","journal-title":"Exp. Eye Res."},{"key":"5934_CR36","doi-asserted-by":"publisher","first-page":"7352","DOI":"10.1167\/iovs.15-17978","volume":"56","author":"WM Petroll","year":"2015","unstructured":"Petroll, W. M., Kivanany, P. B., Hagenasr, D. & Graham, E. K. Corneal fibroblast migration patterns during intrastromal wound healing correlate with ECM structure and alignment. Invest. Ophthalmol. Vis. Sci. 56, 7352\u20137361 (2015).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR37","first-page":"3754","volume":"41","author":"JT Daniels","year":"2000","unstructured":"Daniels, J. T. & Khaw, P. T. Temporal stimulation of corneal fibroblast wound healing activity by differentiating epithelium in vitro. Invest. Ophthalmol. Vis. Sci. 41, 3754\u20133762 (2000).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR38","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1001\/archopht.1981.03930011041011","volume":"99","author":"JG Slingsby","year":"1981","unstructured":"Slingsby, J. G. & Forstot, S. L. Effect of blunt trauma on the corneal endothelium. Arch. Ophthalmol. 99, 1041\u20131043 (1981).","journal-title":"Arch. Ophthalmol."},{"key":"5934_CR39","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1001\/archopht.1978.03910050261014","volume":"96","author":"GW Cibis","year":"1978","unstructured":"Cibis, G. W., Weingeist, T. A. & Krachmer, J. H. Traumatic corneal endothelial rings. Arch. Ophthalmol. 96, 485\u2013488 (1978).","journal-title":"Arch. Ophthalmol."},{"key":"5934_CR40","doi-asserted-by":"crossref","unstructured":"Yi, D. H. & Dana, M. R. Corneal edema after cataract surgery: incidence and etiology. Semin. Ophthalmol. 17, 110\u2013114 (2002).","DOI":"10.1076\/soph.17.3.110.14737"},{"key":"5934_CR41","doi-asserted-by":"publisher","first-page":"268","DOI":"10.2174\/13892037113149990046","volume":"14","author":"B Holzmann","year":"2013","unstructured":"Holzmann, B. Antiinflammatory activities of CGRP modulating innate immune responses in health and disease. Curr. Protein Pept. Sci. 14, 268\u2013274 (2013).","journal-title":"Curr. Protein Pept. Sci."},{"key":"5934_CR42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00726-011-1161-2","volume":"45","author":"B Holzmann","year":"2013","unstructured":"Holzmann, B. Modulation of immune responses by the neuropeptide CGRP. Amino Acids 45, 1\u20137 (2013).","journal-title":"Amino Acids"},{"key":"5934_CR43","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.molimm.2017.08.020","volume":"91","author":"J-X Duan","year":"2017","unstructured":"Duan, J.-X. et al. Calcitonin gene-related peptide exerts anti-inflammatory property through regulating murine macrophages polarization in vitro. Mol. Immunol. 91, 105\u2013113 (2017).","journal-title":"Mol. Immunol."},{"key":"5934_CR44","doi-asserted-by":"publisher","first-page":"108973","DOI":"10.1016\/j.exer.2022.108973","volume":"218","author":"K Asiedu","year":"2022","unstructured":"Asiedu, K. et al. Tear film and ocular surface neuropeptides: characteristics, synthesis, signaling and implications for ocular surface and systemic diseases. Exp. Eye Res. 218, 108973 (2022).","journal-title":"Exp. Eye Res."},{"key":"5934_CR45","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1007\/s00417-015-3120-1","volume":"253","author":"C Chao","year":"2015","unstructured":"Chao, C. et al. Structural and functional changes in corneal innervation after laser in situ keratomileusis and their relationship with dry eye. Graefes Arch. Clin. Exp. Ophthalmol. 253, 2029\u20132039 (2015).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"5934_CR46","first-page":"1039","volume":"18","author":"S Jia","year":"2019","unstructured":"Jia, S. et al. Calcitonin gene\u2011related peptide enhances osteogenic differentiation and recruitment of bone marrow mesenchymal stem cells in rats. Exp. Ther. Med. 18, 1039\u20131046 (2019).","journal-title":"Exp. Ther. Med."},{"key":"5934_CR47","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1167\/iovs.15-18019","volume":"57","author":"J He","year":"2016","unstructured":"He, J. & Bazan, H. E. Neuroanatomy and neurochemistry of mouse cornea. Invest. Ophthalmol. Vis. Sci. 57, 664\u2013674 (2016).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR48","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1001\/archophthalmol.2011.200","volume":"129","author":"A Lambiase","year":"2011","unstructured":"Lambiase, A. et al. Alterations of tear neuromediators in dry eye disease. Arch. Ophthalmol. 129, 981\u2013986, (2011).","journal-title":"Arch. Ophthalmol."},{"key":"5934_CR49","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/0167-0115(86)90054-6","volume":"16","author":"C Wahlestedt","year":"1986","unstructured":"Wahlestedt, C. et al. Calcitonin gene-related peptide in the eye: release by sensory nerve stimulation and effects associated with neurogenic inflammation. Regul. Pept. 16, 107\u2013115 (1986).","journal-title":"Regul. Pept."},{"key":"5934_CR50","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1007\/BF00430415","volume":"234","author":"P Seifert","year":"1996","unstructured":"Seifert, P., Stuppi, S., Spitznas, M. & Weihe, E. Differential distribution of neuronal markers and neuropeptides in the human lacrimal gland. Graefes Arch. Clin. Exp. Ophthalmol. 234, 232\u2013240 (1996).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"5934_CR51","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1002\/cne.902330410","volume":"233","author":"G Terenghi","year":"1985","unstructured":"Terenghi, G. et al. Distribution and origin of calcitonin gene-related peptide (CGRP) immunoreactivity in the sensory innervation of the mammalian eye. J. Comp. Neurol. 233, 506\u2013516 (1985).","journal-title":"J. Comp. Neurol."},{"key":"5934_CR52","first-page":"414","volume":"36","author":"ER Tamm","year":"1995","unstructured":"Tamm, E. R., Fl\u00fcgel-Koch, C., Mayer, B. & L\u00fctjen-Drecoll, E. Nerve cells in the human ciliary muscle: ultrastructural and immunocytochemical characterization. Invest. Ophthalmol. Vis. Sci. 36, 414\u2013426 (1995).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR53","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1177\/0333102420933571","volume":"40","author":"S Wurthmann","year":"2020","unstructured":"Wurthmann, S. et al. Impaired wound healing in a migraine patient as a possible side effect of calcitonin gene-related peptide receptor antibody treatment: a case report. Cephalalgia 40, 1255\u20131260 (2020).","journal-title":"Cephalalgia"},{"key":"5934_CR54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s10194-021-01330-7","volume":"22","author":"JC Ray","year":"2021","unstructured":"Ray, J. C. et al. Inflammatory complications of CGRP monoclonal antibodies: a case series. J. Headache Pain 22, 1\u20138 (2021).","journal-title":"J. Headache Pain"},{"key":"5934_CR55","doi-asserted-by":"publisher","unstructured":"Nagai, N. et al. Instillation of sericin enhances corneal wound healing through the ERK pathway in rat debrided corneal epithelium. Int. J. Mol. Sci. https:\/\/doi.org\/10.3390\/ijms19041123 (2018).","DOI":"10.3390\/ijms19041123"},{"key":"5934_CR56","doi-asserted-by":"publisher","first-page":"5267","DOI":"10.1167\/iovs.06-0642","volume":"47","author":"Z Wang","year":"2006","unstructured":"Wang, Z. et al. Phosphatase-mediated crosstalk control of ERK and p38 MAPK signaling in corneal epithelial cells. Invest. Ophthalmol. Vis. Sci. 47, 5267\u20135275, (2006).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR57","doi-asserted-by":"publisher","first-page":"4044","DOI":"10.1167\/iovs.18-24428","volume":"59","author":"CS Medeiros","year":"2018","unstructured":"Medeiros, C. S., Marino, G. K., Santhiago, M. R. & Wilson, S. E. The corneal basement membranes and stromal fibrosis. Invest. Ophthalmol. Vis. Sci. 59, 4044\u20134053 (2018).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR58","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1016\/j.exer.2007.06.009","volume":"85","author":"SE Wilson","year":"2007","unstructured":"Wilson, S. E., Chaurasia, S. S. & Medeiros, F. W. Apoptosis in the initiation, modulation and termination of the corneal wound healing response. Exp. Eye Res. 85, 305\u2013311 (2007).","journal-title":"Exp. Eye Res."},{"key":"5934_CR59","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.ejphar.2018.10.023","volume":"843","author":"W-Q Li","year":"2019","unstructured":"Li, W.-Q. et al. Calcitonin gene-related peptide inhibits the cardiac fibroblasts senescence in cardiac fibrosis via up-regulating klotho expression. Eur. J. Pharmacol. 843, 96\u2013103 (2019).","journal-title":"Eur. J. Pharmacol."},{"key":"5934_CR60","doi-asserted-by":"publisher","first-page":"1315","DOI":"10.1139\/cjpp-2015-0602","volume":"94","author":"X-W Li","year":"2016","unstructured":"Li, X.-W. et al. Calcitonin gene-related peptide down-regulates bleomycin-induced pulmonary fibrosis. Can. J. Physiol. Pharmacol. 94, 1315\u20131324 (2016).","journal-title":"Can. J. Physiol. Pharmacol."},{"key":"5934_CR61","doi-asserted-by":"publisher","first-page":"14933","DOI":"10.3390\/ijms232314933","volume":"23","author":"N Fortingo","year":"2022","unstructured":"Fortingo, N., Melnyk, S., Sutton, S. H., Watsky, M. A. & Bollag, W. B. Innate immune system activation, inflammation and corneal wound healing. Int. J. Mol. Sci. 23, 14933 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"5934_CR62","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.exer.2014.09.013","volume":"129","author":"AA Torricelli","year":"2014","unstructured":"Torricelli, A. A. & Wilson, S. E. Cellular and extracellular matrix modulation of corneal stromal opacity. Exp. Eye Res. 129, 151\u2013160 (2014).","journal-title":"Exp. Eye Res."},{"key":"5934_CR63","doi-asserted-by":"publisher","first-page":"701","DOI":"10.18240\/ijo.2020.05.02","volume":"13","author":"M Xu","year":"2020","unstructured":"Xu, M. et al. The anti-inflammatory regulation of calcitonin gene-related peptide in mouse Aspergillus fumigatus keratitis. Int. J. Ophthalmol. 13, 701 (2020).","journal-title":"Int. J. Ophthalmol."},{"key":"5934_CR64","doi-asserted-by":"publisher","first-page":"108426","DOI":"10.1016\/j.intimp.2021.108426","volume":"102","author":"K Yuan","year":"2022","unstructured":"Yuan, K. et al. Sensory nerves promote corneal inflammation resolution via CGRP mediated transformation of macrophages to the M2 phenotype through the PI3K\/AKT signaling pathway. Int. Immunopharmacol. 102, 108426 (2022).","journal-title":"Int. Immunopharmacol."},{"key":"5934_CR65","doi-asserted-by":"publisher","first-page":"1145","DOI":"10.1038\/mi.2016.139","volume":"10","author":"J Liu","year":"2017","unstructured":"Liu, J. et al. CCR2\u2212 and CCR2+ corneal macrophages exhibit distinct characteristics and balance inflammatory responses after epithelial abrasion. Mucosal Immunol. 10, 1145\u20131159 (2017).","journal-title":"Mucosal Immunol."},{"key":"5934_CR66","doi-asserted-by":"publisher","first-page":"133","DOI":"10.2147\/IMCRJ.S84865","volume":"8","author":"JH Kim","year":"2015","unstructured":"Kim, J. H., Kim, S. K., Han, S. B., Lee, S. J. & Kim, M. A case of traumatic corneal stromal edema with decreased endothelial cell density. Int. Med. Case Rep. J. 8, 133\u2013135, (2015).","journal-title":"Int. Med. Case Rep. J."},{"key":"5934_CR67","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1007\/s10792-018-0999-7","volume":"38","author":"V Vohra","year":"2018","unstructured":"Vohra, V. & Chawla, H. Corneal endothelial decompensation due to airbag injury. Int. Ophthalmol. 38, 2171\u20132174 (2018).","journal-title":"Int. Ophthalmol."},{"key":"5934_CR68","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1007\/s00417-018-3913-0","volume":"256","author":"Q Wang","year":"2018","unstructured":"Wang, Q. et al. Inflammatory cytokine TNF-\u03b1 promotes corneal endothelium apoptosis via upregulating TIPE2 transcription during corneal graft rejection. Graefes Arch. Clin. Exp. Ophthalmol. 256, 709\u2013715 (2018).","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"5934_CR69","doi-asserted-by":"publisher","first-page":"3477","DOI":"10.1167\/iovs.15-19005","volume":"57","author":"LE Downie","year":"2016","unstructured":"Downie, L. E., Choi, J., Lim, J. K. & Chinnery, H. R. Longitudinal changes to tight junction expression and endothelial cell integrity in a mouse model of sterile corneal inflammation. Invest. Ophthalmol. Vis. Sci. 57, 3477\u20133484, (2016).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR70","doi-asserted-by":"publisher","first-page":"4824699","DOI":"10.1155\/2022\/4824699","volume":"2022","author":"J Meng","year":"2022","unstructured":"Meng, J. et al. Tumor necrosis factor-alpha disrupts Cx43-mediated corneal endothelial gap junction intercellular communication. Oxid. Med. Cell Longev. 2022, 4824699 (2022).","journal-title":"Oxid. Med. Cell Longev."},{"key":"5934_CR71","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1089\/jop.2021.0037","volume":"38","author":"A Chalimeswamy","year":"2022","unstructured":"Chalimeswamy, A. et al. Oxidative stress induces a breakdown of the cytoskeleton and tight junctions of the corneal endothelial cells. J. Ocul. Pharmacol. Ther. 38, 74\u201384 (2022).","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"5934_CR72","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/164_2018_187","volume":"255","author":"AS Wattiez","year":"2019","unstructured":"Wattiez, A. S., Wang, M. & Russo, A. F. CGRP in animal models of migraine. Handb. Exp. Pharmacol. 255, 85\u2013107 (2019).","journal-title":"Handb. Exp. Pharmacol."},{"key":"5934_CR73","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1002\/ejp.1332","volume":"23","author":"F Joubert","year":"2019","unstructured":"Joubert, F. et al. Effects of corneal injury on ciliary nerve fibre activity and corneal nociception in mice: a behavioural and electrophysiological study. Eur. J. Pain 23, 589\u2013602 (2019).","journal-title":"Eur. J. Pain"},{"key":"5934_CR74","doi-asserted-by":"publisher","first-page":"e664","DOI":"10.1097\/PR9.0000000000000664","volume":"3","author":"DM Hegarty","year":"2018","unstructured":"Hegarty, D. M., Hermes, S. M., Morgan, M. M. & Aicher, S. A. Acute hyperalgesia and delayed dry eye after corneal abrasion injury. Pain Rep. 3, e664 (2018).","journal-title":"Pain Rep."},{"key":"5934_CR75","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/j.jtos.2019.07.005","volume":"17","author":"S Shukla","year":"2019","unstructured":"Shukla, S. et al. Therapeutic efficacy of different routes of mesenchymal stem cell administration in corneal injury. Ocul. Surf. 17, 729\u2013736 (2019).","journal-title":"Ocul. Surf."},{"key":"5934_CR76","doi-asserted-by":"publisher","first-page":"2496","DOI":"10.1167\/iovs.02-0851","volume":"44","author":"IK Gipson","year":"2003","unstructured":"Gipson, I. K. et al. Mucin gene expression in immortalized human corneal\u2013limbal and conjunctival epithelial cell lines. Invest. Ophthalmol. Vis. Sci. 44, 2496\u20132506 (2003).","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"5934_CR77","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1097\/ICO.0000000000000418","volume":"34","author":"J Ding","year":"2015","unstructured":"Ding, J., Wirostko, B. & Sullivan, D. A. Human growth hormone promotes corneal epithelial cell migration in vitro. Cornea 34, 686 (2015).","journal-title":"Cornea"},{"key":"5934_CR78","first-page":"107","volume":"7","author":"RL Gendron","year":"2001","unstructured":"Gendron, R. L., Liu, C. Y., Paradis, H., Adams, L. C. & Kao, W. W. MK\/T-1, an immortalized fibroblast cell line derived using cultures of mouse corneal stroma. Mol. Vis. 7, 107\u2013113 (2001).","journal-title":"Mol. Vis."},{"key":"5934_CR79","doi-asserted-by":"publisher","first-page":"10589","DOI":"10.1128\/JVI.79.16.10589-10600.2005","volume":"79","author":"PS Biswas","year":"2005","unstructured":"Biswas, P. S., Banerjee, K., Kim, B., Kinchington, P. R. & Rouse, B. T. Role of inflammatory cytokine-induced cyclooxygenase 2 in the ocular immunopathologic disease herpetic stromal keratitis. J. Virol. 79, 10589\u201310600 (2005).","journal-title":"J. Virol."},{"key":"5934_CR80","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.exer.2005.05.001","volume":"82","author":"PS Biswas","year":"2006","unstructured":"Biswas, P. S., Banerjee, K., Kinchington, P. R. & Rouse, B. T. Involvement of IL-6 in the paracrine production of VEGF in ocular HSV-1 infection. Exp. Eye Res. 82, 46\u201354 (2006).","journal-title":"Exp. Eye Res."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05934-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05934-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05934-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T07:11:44Z","timestamp":1709536304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-024-05934-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,4]]},"references-count":80,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["5934"],"URL":"https:\/\/doi.org\/10.1038\/s42003-024-05934-y","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-3204385\/v1","asserted-by":"object"}]},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,4]]},"assertion":[{"value":"25 July 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 February 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"264"}}