{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,17]],"date-time":"2026-01-17T20:17:08Z","timestamp":1768681028787,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,10]],"date-time":"2022-12-10T00:00:00Z","timestamp":1670630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005703","name":"Akdeniz University Research Unit","doi-asserted-by":"publisher","award":["TSA-2020-4981"],"award-info":[{"award-number":["TSA-2020-4981"]}],"id":[{"id":"10.13039\/501100005703","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pterygium, a disease of the ocular surface, is characterized by the proliferation and invasion of fibrovascular tissue. Chronic inflammation contributes to pterygium occurrence. Sensory neuropeptides of TRPV1-positive nerve fibers are involved in inflammation and corneal wound healing. The possible association between TRPV1 in nerve fibers and neuropeptides such as Substance P (SP) and Vasoactive Intestinal Peptide (VIP) in the recurrence of pterygium has not been examined before. The pterygia from 64 patients were used to determine changes in SP and VIP levels using 10 min acetic-acid extraction that yielded mainly neuronal peptides. There was a sufficient amount of pterygium tissues from the 35 patients for further immunohistochemical analysis of TRPV1 and S100, which is a glial marker to visualize nerve fibers. SP and VIP levels increased markedly in cases with primary and secondary recurrences, and there was a close correlation between SP and VIP levels. TRPV1 expression increased in the epithelium, while stromal expression decreased in recurrences. Nerve fibers were demonstrated mainly in the stroma, and serial sections confirmed the localization of TRPV1 with the nerve fibers. These results together with previous findings demonstrated that the increased epithelial expression of TRPV1 in recurrent pterygia might be involved in the pathogenesis, and the inhibition of epithelial TRPV1 activity may prevent recurrence.<\/jats:p>","DOI":"10.3390\/ijms232415692","type":"journal-article","created":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T01:42:27Z","timestamp":1670809347000},"page":"15692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Changes in TRPV1 Expression as Well as Substance P and Vasoactive Intestinal Peptide Levels Are Associated with Recurrence of Pterygium"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5085-4763","authenticated-orcid":false,"given":"Hatice Deniz","family":"\u0130lhan","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bet\u00fcl","family":"\u00dcnal","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0196-8534","authenticated-orcid":false,"given":"Yusuf","family":"Ayaz","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nuray","family":"Erin","sequence":"additional","affiliation":[{"name":"Department of Medical Pharmacology, Faculty of Medicine, Akdeniz University, Antalya 07070, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,10]]},"reference":[{"key":"ref_1","first-page":"303","article-title":"A hypothesis on the pathogenesis of pterygiums","volume":"10","author":"Wong","year":"1978","journal-title":"Ann. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/S1542-0124(12)70103-9","article-title":"The pathogenesis of pterygium: Current concepts and their therapeutic implications","volume":"6","author":"Chui","year":"2008","journal-title":"Ocul. Surf."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0065-1281(96)80038-9","article-title":"Immunohistochemical localization of basic fibroblast growth factor, platelet derived growth factor, transforming growth factor-beta and tumor necrosis factor-alpha in the pterygium","volume":"98","author":"Kria","year":"1996","journal-title":"Acta Histochem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1007\/s004170050144","article-title":"Growth factors in cultured pterygium fibroblasts: Immunohistochemical and ELISA analysis","volume":"236","author":"Kria","year":"1998","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_5","first-page":"3430","article-title":"UVB-mediated induction of interleukin-6 and -8 in pterygia and cultured human pterygium epithelial cells","volume":"43","author":"Kumar","year":"2002","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/sj.eye.6701728","article-title":"Outcome of pterygium surgery: Analysis over 14 years","volume":"19","author":"Fernandes","year":"2005","journal-title":"Eye"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0014-4835(03)00050-2","article-title":"Corneal nerves: Structure, contents and function","volume":"76","author":"Muller","year":"2003","journal-title":"Exp. Eye Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0161-6420(95)31057-3","article-title":"Scanning slit confocal microscopic observation of cell morphology and movement within the normal human anterior cornea","volume":"102","author":"Auran","year":"1995","journal-title":"Ophthalmology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4482","DOI":"10.1167\/iovs.07-0123","article-title":"The role of substance P in the pathogenesis of pterygia","volume":"48","author":"Chui","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"554195","DOI":"10.3389\/fphys.2020.554195","article-title":"The Mysteries of Capsaicin-Sensitive Afferents","volume":"11","author":"Fischer","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_11","first-page":"1968","article-title":"Effects of capsaicin on corneal wound healing","volume":"31","author":"Gallar","year":"1990","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3109\/02713689408995778","article-title":"Epithelial wound healing in the denervated cornea","volume":"13","author":"Araki","year":"1994","journal-title":"Curr. Eye Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1006\/exer.1994.1145","article-title":"Neurotrophic influences on corneal epithelial cells","volume":"59","author":"Belmonte","year":"1994","journal-title":"Exp. Eye Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1089\/jop.1996.12.417","article-title":"CGRP increases the rate of corneal re-epithelialization in an in vitro whole mount preparation","volume":"12","author":"Mikulec","year":"1996","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_15","first-page":"2252","article-title":"Spontaneous chronic corneal epithelial defects (SCCED) in dogs: Clinical features, innervation, and effect of topical SP, with or without IGF-1","volume":"42","author":"Murphy","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/BF00430415","article-title":"Differential distribution of neuronal markers and neuropeptides in the human lacrimal gland","volume":"234","author":"Seifert","year":"1996","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.1016\/j.ajpath.2018.05.010","article-title":"Vasoactive Intestinal Peptide Promotes Corneal Allograft Survival","volume":"188","author":"Satitpitakul","year":"2018","journal-title":"Am. J. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3215","DOI":"10.1167\/iovs.19-27109","article-title":"Immunohistochemical Characterization of Neurotransmitters in the Episcleral Circulation in Rats","volume":"60","author":"Ladek","year":"2019","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/joa.12001","article-title":"Cutaneous innervation of the human face as assessed by skin biopsy","volume":"222","author":"Nolano","year":"2013","journal-title":"J. Anat."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5285","DOI":"10.3892\/mmr.2017.7246","article-title":"Immunolocalization of cannabinoid receptor type 1 and CB2 cannabinoid receptors, and transient receptor potential vanilloid channels in pterygium","volume":"16","author":"Assimakopoulou","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1349072","DOI":"10.1155\/2020\/1349072","article-title":"Corneal Reinnervation and Sensitivity Recovery after Pterygium Excision","volume":"2020","author":"Zhao","year":"2020","journal-title":"J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.exer.2010.03.010","article-title":"TRPV channels mediate temperature-sensing in human corneal endothelial cells","volume":"90","author":"Mergler","year":"2010","journal-title":"Exp. Eye Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1002\/jcp.22514","article-title":"Thermosensitive transient receptor potential channels in human corneal epithelial cells","volume":"226","author":"Mergler","year":"2011","journal-title":"J. Cell Physiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1167\/iovs.10-5801","article-title":"TRPV1 activation is required for hypertonicity-stimulated inflammatory cytokine release in human corneal epithelial cells","volume":"52","author":"Pan","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1001\/archopht.1997.01100160405001","article-title":"Effect of pterygium morphology on pterygium recurrence in a controlled trial comparing conjunctival autografting with bare sclera excision","volume":"115","author":"Tan","year":"1997","journal-title":"Arch. Ophthalmol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1159\/000493544","article-title":"Dry-Eye Disease in Recurrent Pterygium","volume":"61","author":"Tan","year":"2019","journal-title":"Ophthalmic. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1167\/iovs.16-19170","article-title":"Upregulation of Transient Receptor Potential Vanilloid Type-1 Channel Activity and Ca2+ Influx Dysfunction in Human Pterygial Cells","volume":"57","author":"Garreis","year":"2016","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1167\/iovs.62.9.6","article-title":"Distribution of Corneal TRPV1 and Its Association With Immune Cells During Homeostasis and Injury","volume":"62","author":"Jiao","year":"2021","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/S1542-0124(12)70112-X","article-title":"Nerves and sensations from the eye surface","volume":"2","author":"Belmonte","year":"2004","journal-title":"Ocul. Surf."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"232","DOI":"10.2144\/04372ST04","article-title":"Parameters affecting substance P measurement in heart, lung, and skin","volume":"37","author":"Erin","year":"2004","journal-title":"Biotechniques"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6783","DOI":"10.1167\/iovs.14-14553","article-title":"NK1 receptor antagonists as a new treatment for corneal neovascularization","volume":"55","author":"Bignami","year":"2014","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nm.1909","article-title":"A new role of substance P as an injury-inducible messenger for mobilization of CD29(+) stromal-like cells","volume":"15","author":"Hong","year":"2009","journal-title":"Nat. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1002\/(SICI)1097-4652(200002)182:2<189::AID-JCP7>3.0.CO;2-9","article-title":"Substance P-induced cadherin expression and its signal transduction in a cloned human corneal epithelial cell line","volume":"182","author":"Aizawa","year":"2000","journal-title":"J. Cell Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.preteyeres.2015.01.004","article-title":"Peptide therapies for ocular surface disturbances based on fibronectin-integrin interactions","volume":"47","author":"Nishida","year":"2015","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4262","DOI":"10.2337\/db14-0163","article-title":"Substance P promotes diabetic corneal epithelial wound healing through molecular mechanisms mediated via the neurokinin-1 receptor","volume":"63","author":"Yang","year":"2014","journal-title":"Diabetes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/sj.bjp.0700923","article-title":"The NK1 receptor and its participation in the synergistic enhancement of corneal epithelial migration by substance P and insulin-like growth factor-1","volume":"120","author":"Nakamura","year":"1997","journal-title":"Br. J. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1006\/exer.1999.0652","article-title":"Vasoactive intestinal polypeptide (VIP) innervation of the human eyelid glands","volume":"68","author":"Seifert","year":"1999","journal-title":"Exp. Eye Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jtos.2014.01.005","article-title":"The neurobiology of the meibomian glands","volume":"12","author":"Cox","year":"2014","journal-title":"Ocul. Surf."},{"key":"ref_39","first-page":"2270","article-title":"Presence of nerves and their receptors in mouse and human conjunctival goblet cells","volume":"42","author":"Diebold","year":"2001","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_40","first-page":"6043710","article-title":"The Anti-Inflammatory Mediator, Vasoactive Intestinal Peptide, Modulates the Differentiation and Function of Th Subsets in Rheumatoid Arthritis","volume":"2018","author":"Carrion","year":"2018","journal-title":"J. Immunol. Res."},{"key":"ref_41","first-page":"419","article-title":"Vasoactive intestinal peptide: A potential target for antiviral therapy","volume":"74","author":"He","year":"2022","journal-title":"Sheng Li Xue Bao"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jansen, M.I., Thomas Broome, S., and Castorina, A. (2022). Exploring the Pro-Phagocytic and Anti-Inflammatory Functions of PACAP and VIP in Microglia: Implications for Multiple Sclerosis. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23094788"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"13079","DOI":"10.1074\/jbc.M113.536953","article-title":"The endocannabinoid\/endovanilloid N-arachidonoyl dopamine (NADA) and synthetic cannabinoid WIN55,212-2 abate the inflammatory activation of human endothelial cells","volume":"289","author":"Wilhelmsen","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12974-022-02485-z","article-title":"N-Oleoyl dopamine induces IL-10 via central nervous system TRPV1 and improves endotoxemia and sepsis outcomes","volume":"19","author":"Joffre","year":"2022","journal-title":"J. Neuroinflammation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.regpep.2008.10.006","article-title":"Differentiation of neuronal from non-neuronal Substance P","volume":"152","author":"Erin","year":"2009","journal-title":"Regul. Pept."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15692\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:37:53Z","timestamp":1760146673000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,10]]},"references-count":45,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415692"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415692","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,10]]}}}