Tear proteomics reveals the molecular basis of the efficacy of human recombinant nerve growth factor treatment for Neurotrophic Keratopathy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35075190", "kind": "science-record", "revision": 4, "content_hash": "sha256:9525688bda5b21ea712925562361a892b9a7817c356ef90cd1d77f0468faecaf", "created_at": "2026-11-01T17:36:48Z", "updated_at": "2026-11-01T21:27:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Tear proteomics reveals the molecular basis of the efficacy of human recombinant nerve growth factor treatment for Neurotrophic Keratopathy.", "doi": "10.1038/s41598-022-05229-4", "pmid": "35075190", "authors": ["Damiana Pieragostino", "Manuela Lanzini", "Ilaria Cicalini", "Maria Concetta Cufaro", "Verena Damiani", "Leonardo Mastropasqua", "Vincenzo De Laurenzi", "Mario Nubile", "Paola Lanuti", "Giuseppina Bologna", "Luca Agnifili", "Piero Del Boccio"], "journal": "Scientific reports", "year": 2022, "abstract": "Neurotrophic Keratopathy (NK), classified as an orphan disease (ORPHA137596), is a rare degenerative corneal disease characterized by epithelial instability and decreased corneal sensitivity caused by the damage to the corneal nerves. The administration of human recombinant nerve growth factor (rhNGF) eye drops, as a licensed-in-Europe specific medication for treatment of moderate and severe NK, has added promising perspectives to the management of this disorder by providing a valid alternative to the neurotization surgery. However, few studies have been conducted to the molecular mechanism underlying the response to the treatment. Here, we carried out tears proteomics to highlight the protein expression during pharmacological treatment of NK (Data are available via ProteomeXchange with identifier PXD025408).Our data emphasized a proteome modulation during rhNGF treatment related to an increase in DNA synthesis, an activation of both BDNF signal and IL6 receptor. Furthermore, the amount of neuronal Extracellular Vesicles EVs (CD171+) correlated with the EVs carrying IL6R (CD126+) together associated to the inflammatory EVs (CD45+) in tears. Such scenario determined drug response, confirmed by an in vivo confocal microscopy analysis, showing an increase in length, density and number of nerve fiber branches during treatment. In summary, rhNGF treatment seems to determine an inflammatory micro-environment, mediated by functionalized EVs, defining the drug response by stimulating protein synthesis and fiber regeneration.", "claims": [{"id": "claim-method", "statement": "Kruskal–Wallis test with Dunn’s Multiple Comparison post-test was performed for comparisons between the three different clinical groups, using GraphPad Prism (GraphPad software, Inc. USA).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35075190", "locator": "sections[16] \"Statistical analysis\" paragraph 2", "quote": "Kruskal–Wallis test with Dunn’s Multiple Comparison post-test was performed for comparisons between the three different clinical groups, using GraphPad Prism (GraphPad software, Inc. USA)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner33 repository with the dataset identifier PXD025408.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35075190", "locator": "sections[12] \"Proteomics analysis and data processing\" paragraph 4", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner33 repository with the dataset identifier PXD025408."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The length (Panel A), density (Panel B) and number of ramifications (Panel C) of nerve fibers increase during treatment (T4) (p-value < 0.05) and, more evidently (p-value < 0.01) at the end of the therapeutic course (T8).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35075190", "locator": "sections[7] \"In vivo confocal microscopy analysis corroborates proteomics results\" paragraph 2", "quote": "The length (Panel A), density (Panel B) and number of ramifications (Panel C) of nerve fibers increase during treatment (T4) (p-value < 0.05) and, more evidently (p-value < 0.01) at the end of the therapeutic course (T8)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The length (Panel A), density (Panel B) and number of ramifications (Panel C) of nerve fibers increase during treatment (T4) (p-value < 0.05) and, more evidently (p-value < 0.01) at the end of the therapeutic course (T8).", "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:35075190"], "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": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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