{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:51:02Z","timestamp":1790398262608,"version":"4.1.0"},"reference-count":33,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T00:00:00Z","timestamp":1723161600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vancouver Coastal Health Research Institute, Faculty of Medicine"},{"name":"NSERC"},{"name":"CIHR"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pterygium is often associated with chronic ultraviolet (UV) radiation exposure and characterized by the overgrowth of conjunctiva and extracellular matrix (ECM) remodeling. Notably, several studies in the skin have demonstrated that chronic UV radiation can upregulate Granzyme B (GrB) expression and increase ECM degradation. The aim of this study was to compare GrB expression between pterygium and healthy controls and to further link this GrB expression to mast cells. Post-mortem pterygium tissues and conjunctival tissues from age-matched controls were used to assess GrB expression via immunofluorescence and microscopy. We found a significantly higher density of GrB+ cells from pterygium specimens compared to healthy controls. Furthermore, many of the GrB+ cells in pterygium specimens co-expressed tryptase, a mast cell marker. These findings suggest a role for conjunctival mast cell-secreted GrB in the pathogenesis of pterygium and highlight GrB as a possible therapeutic target in delaying or halting pterygium progression.<\/jats:p>","DOI":"10.3390\/ijms25168679","type":"journal-article","created":{"date-parts":[[2024,8,9]],"date-time":"2024-08-09T07:59:07Z","timestamp":1723190347000},"page":"8679","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Granzyme B Expression in Conjunctiva of Patients with Pterygium"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6223-7607","authenticated-orcid":false,"given":"Yoojin","family":"Choi","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isa","family":"Samad","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC V5Z 3N9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2744-0642","authenticated-orcid":false,"given":"Harshini","family":"Chakravarthy","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC V5Z 3N9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Matsubara","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC V5Z 3N9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6985-2816","authenticated-orcid":false,"given":"David J.","family":"Granville","sequence":"additional","affiliation":[{"name":"ICORD Centre and Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1197-8026","authenticated-orcid":false,"given":"Sonia N.","family":"Yeung","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC V5Z 3N9, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.survophthal.2018.03.001","article-title":"Prevalence and Risk Factors of Pterygium: A Systematic Review and Meta-Analysis","volume":"63","author":"Rezvan","year":"2018","journal-title":"Surv. Ophthalmol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1038\/eye.2008.200","article-title":"Prevalence and Risk Factors of Pterygium and Pinguecula: The Tehran Eye Study","volume":"23","author":"Fotouhi","year":"2009","journal-title":"Eye"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"6617","DOI":"10.1167\/iovs.11-8947","article-title":"Prevalence of and Risk Factors for Pterygium in Rural Adult Chinese Populations of the Bai Nationality in Dali: The Yunnan Minority Eye Study","volume":"53","author":"Zhong","year":"2012","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mart\u00edn-L\u00f3pez, J., P\u00e9rez-Rico, C., Benito-Mart\u00ednez, S., P\u00e9rez-K\u00f6hler, B., Buj\u00e1n, J., and Pascual, G. (2021). The Role of the Stromal Extracellular Matrix in the Development of Pterygium Pathology: An Update. J. Clin. Med., 10.","DOI":"10.3390\/jcm10245930"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1136\/bjophthalmol-2017-310288","article-title":"Comparison among Adjuvant Treatments for Primary Pterygium: A Network Meta-Analysis","volume":"102","author":"Fonseca","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1007\/s10384-018-0582-9","article-title":"Risk Factors for Pterygium Recurrence after Limbal-Conjunctival Autografting: A Retrospective, Single-Centre Investigation","volume":"62","author":"Aidenloo","year":"2018","journal-title":"Jpn. J. Ophthalmol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jtos.2014.01.001","article-title":"Surgical Management of Pterygium","volume":"12","author":"Janson","year":"2014","journal-title":"Ocul. Surf."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1159\/000095863","article-title":"Flow Cytometrical Analysis of Adhesion Molecules, T-Lymphocyte Subpopulations and Inflammatory Markers in Pterygium","volume":"220","author":"Tekelioglu","year":"2006","journal-title":"Ophthalmologica"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1007\/s12325-008-0056-4","article-title":"The Presence of T-Lymphocyte Subpopulations (CD4 and CD8) in Pterygia: Evaluation of the Inflammatory Response","volume":"25","author":"Awdeh","year":"2008","journal-title":"Adv. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1076\/ocii.11.2.115.15913","article-title":"The Roles of T-Lymphocyte Subpopulations (CD4 and CD8), Intercellular Adhesion Molecule-1 (ICAM-1), HLA-DR Receptor, and Mast Cells in Etiopathogenesis of Pterygium","volume":"11","author":"Beden","year":"2003","journal-title":"Ocul. Immunol. Inflamm."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"100123","DOI":"10.1016\/j.labinv.2023.100123","article-title":"Granzyme B Contributes to Choroidal Neovascularization and Age-Related Macular Degeneration Through Proteolysis of Thrombospondin-1","volume":"103","author":"Obasanmi","year":"2023","journal-title":"Lab. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1097\/01.MP.0000067424.12280.BC","article-title":"Granzyme B in Atherosclerosis and Transplant Vascular Disease: Association with Cell Death and Atherosclerotic Disease Severity","volume":"16","author":"Choy","year":"2003","journal-title":"Mod. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1093\/infdis\/jiz538","article-title":"Granzyme B Produced by Natural Killer Cells Enhances Inflammatory Response and Contributes to the Immunopathology of Cutaneous Leishmaniasis","volume":"221","author":"Campos","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1111\/acel.12298","article-title":"Granzyme B Mediates Both Direct and Indirect Cleavage of Extracellular Matrix in Skin after Chronic Low-dose Ultraviolet Light Irradiation","volume":"14","author":"Parkinson","year":"2015","journal-title":"Aging Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13525","DOI":"10.1074\/jbc.M512694200","article-title":"Human Keratinocytes Acquire Cellular Cytotoxicity under UV-B Irradiation","volume":"281","author":"Jean","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Matsubara, J.A., Tian, Y., Cui, J.Z., Zeglinski, M.R., Hiroyasu, S., Turner, C.T., and Granville, D.J. (2020). Retinal Distribution and Extracellular Activity of Granzyme B: A Serine Protease That Degrades Retinal Pigment Epithelial Tight Junctions and Extracellular Matrix Proteins. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00574"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1167\/iovs.61.4.7","article-title":"UV-B-Induced Inflammasome Activation Can Be Prevented by Cis-Urocanic Acid in Human Corneal Epithelial Cells","volume":"61","author":"Korhonen","year":"2020","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"108194","DOI":"10.1016\/j.exer.2020.108194","article-title":"Relative Gene Expression Analysis of Human Pterygium Tissues and UV Radiation-Evoked Gene Expression Patterns in Corneal and Conjunctival Cells","volume":"199","author":"Shibata","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/s41467-020-20604-3","article-title":"Granzyme B Inhibition Reduces Disease Severity in Autoimmune Blistering Diseases","volume":"12","author":"Hiroyasu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_21","first-page":"5","article-title":"The Pathophysiology of Photoaging of the Skin","volume":"75","author":"Fisher","year":"2005","journal-title":"Cutis"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1111\/j.1582-4934.2007.00050.x","article-title":"Neovascularization and Mast Cells with Tryptase Activity Increase Simultaneously in Human Pterygium","volume":"11","author":"Ribatti","year":"2007","journal-title":"J. Cell Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1097\/00003226-199709000-00010","article-title":"Immunolocalization of bFGF in Pterygia: Association with Mast Cells","volume":"16","author":"Powers","year":"1997","journal-title":"Cornea"},{"key":"ref_24","first-page":"662","article-title":"Pterygium and mast cells--mast cell number, phenotype, and localization of stem cell factor","volume":"101","author":"Nakagami","year":"1997","journal-title":"Nippon. Ganka Gakkai Zasshi"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"285","DOI":"10.5935\/0004-2749.20140072","article-title":"The Role of Mast Cells in Vascularized Recurrent Pterygium","volume":"77","author":"Celebi","year":"2014","journal-title":"Arq. Bras. Oftalmol."},{"key":"ref_26","first-page":"71","article-title":"Overexpression of Collagenase (MMP-1) and Stromelysin (MMP-3) by Pterygium Head Fibroblasts","volume":"119","author":"Li","year":"2001","journal-title":"Arch. Ophthalmol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1167\/iovs.08-3147","article-title":"Increased Expression of Gelatinase (MMP-2 and MMP-9) in Pterygia and Pterygium Fibroblasts with Disease Progression and Activation of Protein Kinase, C","volume":"50","author":"Yang","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1021\/acsptsci.2c00125","article-title":"Matrix Metalloproteinase-14 as an Instigator of Fibrosis in Human Pterygium and Its Pharmacological Intervention","volume":"5","author":"Masitas","year":"2022","journal-title":"ACS Pharmacol. Transl. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kim, Y.-H., Jung, J.-C., Gum, S.I., Park, S.-B., Ma, J.Y., Kim, Y.I., Lee, K.W., and Park, Y.J. (2017). Inhibition of Pterygium Fibroblast Migration and Outgrowth by Bevacizumab and Cyclosporine A Involves Down-Regulation of Matrix Metalloproteinases-3 and -13. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0169675"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.tips.2013.02.004","article-title":"Missing the Target: Matrix Metalloproteinase Antitargets in Inflammation and Cancer","volume":"34","author":"Dufour","year":"2013","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41514-021-00059-6","article-title":"Granzyme B Mediates Impaired Healing of Pressure Injuries in Aged Skin","volume":"7","author":"Turner","year":"2021","journal-title":"NPJ Aging Mech. Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.exger.2011.02.004","article-title":"Granzyme B Contributes to Extracellular Matrix Remodeling and Skin Aging in Apolipoprotein E Knockout Mice","volume":"46","author":"Hiebert","year":"2011","journal-title":"Exp. Gerontol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Dubchak, E., Obasanmi, G., Zeglinski, M.R., Granville, D.J., Yeung, S.N., and Matsubara, J.A. (2022). Potential Role of Extracellular Granzyme B in Wet Age-Related Macular Degeneration and Fuchs Endothelial Corneal Dystrophy. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.980742"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8679\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:32:35Z","timestamp":1760110355000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/16\/8679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,9]]},"references-count":33,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2024,8]]}},"alternative-id":["ijms25168679"],"URL":"https:\/\/doi.org\/10.3390\/ijms25168679","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,9]]}}}