Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36930145", "kind": "science-record", "revision": 2, "content_hash": "sha256:cb4c1147ecb78c35d49ec507cfb9f12565ae2cbd3776bafc2cc986dcb272e483", "created_at": "2026-11-01T19:01:34Z", "updated_at": "2026-11-01T21:30:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Scleral Proteome in Noninfectious Scleritis Unravels Upregulation of Filaggrin-2 and Signs of Neovascularization.", "doi": "10.1167/iovs.64.3.27", "pmid": "36930145", "authors": ["Daphne P C Vergouwen", "Josianne C Ten Berge", "Coskun Guzel", "Thierry P P van den Bosch", "Robert M Verdijk", "Aniki Rothova", "Theo M Luider", "Marco W J Schreurs"], "journal": "Investigative ophthalmology & visual science", "year": 2023, "abstract": "Purpose: Scleritis is a severe inflammatory ocular disorder with unknown pathogenesis. We investigated healthy sclera as well as sclera affected by noninfectious scleritis for differentially expressed proteins using a mass spectrometry approach.\nMethods: We collected scleral samples of enucleated eyes due to severe noninfectious scleritis (n = 3), and control scleral tissues (n = 5), all exenterated eyes for eyelid carcinomas (n = 4), or choroidal melanoma (n = 1) without scleral invasion. Samples were prepared for the nano liquid-chromatography mass spectrometer (LC-MS), data were analyzed using proteomics software (Scaffold), and is available via ProteomeXchange (identifier PXD038727). Samples were also stained for immuno-histopathological evaluation.\nResults: Mass spectrometry identified 629 proteins within the healthy and diseased scleral tissues, whereof collagen type XII, VI, and I were the most abundantly expressed protein. Collagen type II-XII was also present. Filaggrin-2, a protein that plays a crucial role in epidermal barrier function, was found upregulated in all scleritis cases. In addition, other epithelial associated proteins were upregulated (such as keratin 33b, 34, and 85, epiplakin, transglutaminase-3, galectin 7, and caspase-14) in scleritis. Further, upregulated proteins involved in regulation of the cytoskeleton (vinculin and myosin 9), and housekeeping proteins were found (elongation factor-2 and cytoplasmic dynein 1) in our study. Upregulation of filaggrin-2 and myosin-9 was confirmed with immunohistochemistry, the latter protein showing co-localization with the endothelial cell marker ETC-related gene (ERG), indicating neovascularization in scleral tissue affected by scleritis.\nConclusions: We found upregulation of filaggrin-2 and signs of neovascularization in scleral tissue of patients with noninfectious scleritis. Further research, ideally including more scleritis cases, is needed to validate our findings.", "claims": [{"id": "claim-method", "statement": "An independent sample t-test on normalized total spectral counts was used to identify differentially expressed proteins, considering multiple testing correction using the Benjamini-Hochberg method.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36930145", "locator": "sections[7] \"Bioinformatics\" paragraph 2", "quote": "An independent sample t-test on normalized total spectral counts was used to identify differentially expressed proteins, considering multiple testing correction using the Benjamini-Hochberg method."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE14 partner repository with the dataset identifier PXD038727 and 10.6019/PXD038727.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36930145", "locator": "sections[7] \"Bioinformatics\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE14 partner repository with the dataset identifier PXD038727 and 10.6019/PXD038727."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Filaggrin-2 was upregulated and signs of neovascularization were found in scleral tissue affected by noninfectious scleritis.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36930145", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "We found upregulation of filaggrin-2 and signs of neovascularization in scleral tissue of patients with noninfectious scleritis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Filaggrin-2 was upregulated and signs of neovascularization were found in scleral tissue affected by noninfectious scleritis.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36930145"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "blocked", "blocked_on": "data:accession_absent", "description": "The GEO series accession resolves and its sample accessions are listed. 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