{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:57:44Z","timestamp":1781110664749,"version":"3.54.1"},"reference-count":77,"publisher":"S. Karger AG","issue":"1","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ophthalmic Res"],"abstract":"<jats:p>Introduction: Tear-deficient dry eye disease (DED), including Sj\u00f6gren\u2019s syndrome and ocular graft-versus-host disease (oGVHD), is often refractory to therapy. We tested whether platelet-derived growth factor (PDGF) isoform imbalance, quantified as a PDGF-AB\/BB: PDGF-AA ratio (\u201cPDGF Ratio\u201d), is associated with innate activation and corneal epitheliopathy. Methods: Tear samples from 151 participants were profiled across two independent assay runs: discovery (n = 79) and replication (n = 72). Data were harmonized as within-plate rank percentiles. Plate-adjusted mediation tested whether the PDGF Ratio mediated associations between tear-deficient status and an innate NF-\u03baB composite (IL-18\/IL-6\/IL-8\/TNF-\u03b1) and National Eye Institute (NEI) scale graded corneal staining. A parallel model for staining included Schirmer scores to distinguish trophic from aqueous volume deficiency. Results: The PDGF Ratio differed significantly across diagnostic groups (Kruskal-Wallis p &lt; 0.001), driven by concurrent PDGF-AA depletion (median rank 0.69 healthy vs. 0.19 oGVHD) and PDGF-AB\/BB enrichment (0.18 vs. 0.62; both p &lt; 0.001). High ratio co-occurred with higher innate cytokine ranks and lower EGF and IFN-\u03b3. In pooled mediation, the ratio accounted for 62.8% of the tear-deficient association with innate inflammation (indirect 0.168; 95% CI 0.118\u20130.225) and 34.2% of the association with corneal staining (indirect 0.117; 95% CI 0.055\u20130.190). The staining pathway remained significant after accounting for Schirmer (indirect 0.113; 95% CI 0.050\u20130.185). Conclusion: Tear-deficient DED exhibits a reproducible PDGF isoform imbalance that statistically accounts for substantial portions of innate activation and corneal staining. These findings support the PDGF Ratio as a coherent candidate biomarker and therapeutic axis for isoform-selective rebalancing.<\/jats:p>","DOI":"10.1159\/000551958","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T16:01:25Z","timestamp":1775836885000},"page":"129-162","source":"Crossref","is-referenced-by-count":0,"title":["Platelet-Derived Growth Factor Isoform Imbalance Is Associated with Innate Inflammation and Corneal Epitheliopathy in Dry Eye Disease"],"prefix":"10.1159","volume":"69","author":[{"given":"Zeenal","family":"Dabre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyung-Geun","family":"Moon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Sheth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuvanachandra","family":"Pasupuleti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Mun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiera","family":"Byrne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Mun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Hernandez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Ascencio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Shehadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Flavin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6878-521X","authenticated-orcid":false,"given":"Simon","family":"Kaja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Jain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2017.07.010"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.3238\/arztebl.2017.0354"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1038\/s41409-024-02321-3"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26188824"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2025.04.006"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2022-067007"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.clae.2025.102482"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2020.05.009"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2013.08.013"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101442"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2012.02.003"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2025.110574"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.090318"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2021.11.002"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10430"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2019.03.010"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.3390\/biom14010102"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajo.2013.04.003"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2020.1767792"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0126277"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2010.06.016"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700545"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500437200"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-44990-0"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.630536"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.867516"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2019.1662678"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03531-2"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2005.10.013"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1038\/nature08780"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2012.04.006"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0703328"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1684290"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.4.8"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.13-12844"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1159\/000550166"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtos.2019.10.004"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2017.11.007"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.24.309"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.4.1283"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.14-14818"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00054.2019"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1007\/BF00947012"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.21783"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2021.11877"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208516"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1817398"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.4196\/kjpp.2024.28.5.449"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2021.12798"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.19540\/j.cnki.cjcmm.20240110.502"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1016\/s0026-2862(03)00004-9"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-017-1238-8"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2020-047081"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.1111\/jfbc.14329"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2024.110073"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.1076\/ceyr.16.8.825.8984"},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4338"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1002\/art.39859"},{"key":"ref59","doi-asserted-by":"publisher","DOI":"10.1038\/srep03419"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.118.5.615"},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1080\/09273948.2022.2046794"},{"key":"ref62","doi-asserted-by":"publisher","DOI":"10.1007\/s10792-020-01489-z"},{"key":"ref63","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.912010"},{"key":"ref64","doi-asserted-by":"publisher","DOI":"10.1080\/02713683.2020.1715445"},{"key":"ref65","doi-asserted-by":"publisher","DOI":"10.2147\/OTT.S239252"},{"key":"ref66","doi-asserted-by":"publisher","DOI":"10.3758\/brm.40.3.879"},{"key":"ref67","doi-asserted-by":"publisher","DOI":"10.1207\/s15327906mbr3901_4"},{"key":"ref68","doi-asserted-by":"publisher","DOI":"10.1037\/met0000086"},{"key":"ref69","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-16736"},{"key":"ref70","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2022.07.023"},{"key":"ref71","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.64.14.9"},{"key":"ref72","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1092108"},{"key":"ref73","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2009.04.003"},{"key":"ref74","doi-asserted-by":"publisher","DOI":"10.1006\/exer.2001.0999"},{"key":"ref75","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.66.11.61"},{"key":"ref76","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7641"},{"key":"ref77","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114491"}],"container-title":["Ophthalmic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/000551958","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:01:06Z","timestamp":1781107266000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000551958"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,10]]},"references-count":77,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000551958","archive":["Portico"],"relation":{},"ISSN":["0030-3747","1423-0259"],"issn-type":[{"value":"0030-3747","type":"print"},{"value":"1423-0259","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,10]]}}}