{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:47:03Z","timestamp":1790444823279,"version":"4.1.0"},"reference-count":102,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T00:00:00Z","timestamp":1747353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical University of Silesia"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The cornea, a highly innervated and avascular ocular tissue, relies on intricate neuro-immune interactions to maintain homeostasis. Among key neuromediators, substance P (SP)\u2014a neuropeptide belonging to the tachykinin family\u2014plays a dual role in corneal physiology and pathology. This review synthesizes current knowledge on SP\u2019s involvement in corneal innervation, epithelial homeostasis, immune regulation, neovascularization, and wound healing, while highlighting its dichotomous effects in both promoting tissue repair and exacerbating inflammation. SP, primarily signaling through the neurokinin-1 receptor (NK1R), influences corneal epithelial proliferation, barrier function, and wound healing by modulating cytokines, chemokines, and growth factors. However, its overexpression is linked to pain sensitization, inflammatory keratitis, and corneal neovascularization, driven by interactions with immune cells (e.g., mast cells, neutrophils) and pro-angiogenic factors (e.g., VEGF). Clinical studies demonstrate altered SP levels in dry eye disease, neurotrophic keratitis, and post-refractive surgery, correlating with nerve damage and ocular surface dysfunction. Emerging therapies targeting SP pathways- such as NK1R antagonists (e.g., fosaprepitant) and SP-IGF-1 combinations-show promise for treating neurotrophic ulcers but face challenges due to SP\u2019s context-dependent actions. Future research should clarify the roles of NK2R\/NK3R receptors and optimize SP-based interventions to balance its reparative and inflammatory effects. Understanding SP\u2019s multifaceted mechanisms could advance the development of therapies for corneal diseases, particularly those involving sensory neuropathy and immune dysregulation.<\/jats:p>","DOI":"10.3390\/biom15050729","type":"journal-article","created":{"date-parts":[[2025,5,16]],"date-time":"2025-05-16T06:57:28Z","timestamp":1747378648000},"page":"729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The Role of Substance P in Corneal Homeostasis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1109-176X","authenticated-orcid":false,"given":"Irmina","family":"Jastrz\u0119bska-Miazga","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Kornel Gibinski University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartosz","family":"Machna","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Laboratory for Translational Research in Ophthalmology, Department of Ophthalmology, Kornel Gibinski University Clinical Center, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7579-2546","authenticated-orcid":false,"given":"Dorota","family":"Wygl\u0119dowska-Promie\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Kornel Gibinski University Clinical Center, Medical University of Silesia, 40-514 Katowice, Poland"},{"name":"Department of Ophthalmology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8528-955X","authenticated-orcid":false,"given":"Adrian","family":"Sm\u0119dowski","sequence":"additional","affiliation":[{"name":"Laboratory for Translational Research in Ophthalmology, Department of Ophthalmology, Kornel Gibinski University Clinical Center, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Department of Pediatric Ophthalmology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"Department of Pediatric Ophthalmology, Kornel Gibinski University Clinical Center, Medical University of Silesia, 40-055 Katowice, Poland"},{"name":"GlaucoTech Co., 40-282 Katowice, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1016\/j.jcrs.2010.12.037","article-title":"Anatomy and physiology of the cornea","volume":"37","author":"DelMonte","year":"2011","journal-title":"J. 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