Altered pattern of proteolysis in rhegmatogenous retinal detachment by mining of N-termini datasets from vitreous humor proteome.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41087496", "kind": "science-record", "revision": 4, "content_hash": "sha256:c7748f6f30b4391b0d912e699d9f7d34c5787788f5f78668dcefde5998a5c45d", "created_at": "2026-11-01T20:31:08Z", "updated_at": "2026-11-01T22:57:18Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Altered pattern of proteolysis in rhegmatogenous retinal detachment by mining of N-termini datasets from vitreous humor proteome.", "doi": "10.1038/s41598-025-19857-z", "pmid": "41087496", "authors": ["Gabriele Antonio Zingale", "Sara Giammaria", "Irene Pandino", "Luca Placentino", "Guido Ripandelli", "Grazia Raffaella Tundo", "Giuseppe Grasso", "Alessio Bocedi", "Peter A Bell", "Tommaso Rossi", "Diego Sbardella"], "journal": "Scientific reports", "year": 2025, "abstract": "Rhegmatogenous Retinal Detachment (RRD) is a severe ocular condition characterized by the detachment of the neurosensory retina from the retinal pigment epithelium and caused by retinal tears. Pars Plana Vitrectomy (PPV) is the standard surgical procedure for RRD, and is intended to remove the vitreous gel, which shapes the eye, and provides mechanical and nutritional support to the retina. The study of the vitreous proteome isolated from RRD patients may help decipher the pathobiology of the disease and that of its complications, such as proliferative vitreo-retinopathy (PVR), which predispose to recurrent retinal detachment (observed in 20% of cases), a sight threatening condition. Herein, we set up a pilot shot-gun proteomics study (Data are available via ProteomeXchange with identifier PXD057155) to investigate the perturbations of vitreous proteome comparing RRD patients (n = 8) to patients affected by idiopathic Epiretinal Membranes (ERM), used as controls (n = 8). Spectra were first searched and analyzed to identify proteome perturbations. Thereafter, starting from the hypothesis that RRD could be sustained by altered proteolytic processing of structural and non-structural elements of vitreous gel, N- and C-termini were mined to uncover endogenous proteolytic events. Our search revealed a comprehensive array of proteolytic events and sites across numerous proteins. While some of these were previously documented in different biological samples (like plasma, cell models, etc.), our findings point to new, potentially specific cleavage sites on macromolecular components unique to the vitreous fluid and retinal layers (e.g., interphotoreceptor matrix proteoglycan 1 and 2). Comparison between the N- and C-termini landscapes and the perturbations of global proteome highlighted robust alterations of the repertoire of cleaved proteins between RRD patients and reference control subjects. Additional immunoblotting studies on a selection of proteins envisage that RRD is characterized by unbalanced proteolysis of structural and non-structural components involved in the regulation of immune processes, proteolytic control and, particularly, angiogenesis.", "claims": [{"id": "claim-method", "statement": "A moderated Bayesian t-test (LIMMA) was then used to identify differentially expressed proteins (DEPs) between the two experimental groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41087496", "locator": "sections[6] \"Statistical analysis\" paragraph 3", "quote": "A moderated Bayesian t-test (LIMMA) was then used to identify differentially expressed proteins (DEPs) between the two experimental groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "“The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD057155 and 10.6019/PXD057155\"45.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41087496", "locator": "sections[19] \"Data availability\" paragraph 2", "quote": "“The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD057155 and 10.6019/PXD057155\"45."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using a moderated Bayesian t-test, the study identified 93 differentially expressed proteins between RRD and control vitreous humor and revealed altered proteolytic processing of structural and non-structural vitreous components.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41087496", "locator": "sections[1] \"Introduction\" paragraph 10", "quote": "Without immunodepleting for most abundant proteins and working on a single-subject scale, using a moderated Bayesian t-test we identified a total 93 differentially expressed proteins (DEPs) between RRD and Control VH, uncovering precise alterations of key pathways for cell metabolism and tissue homeostasis."}, {"asset": "source:pmid:41087496", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Comparison between the N- and C-termini landscapes and the perturbations of global proteome highlighted robust alterations of the repertoire of cleaved proteins between RRD patients and reference control subjects."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Using a moderated Bayesian t-test, the study identified 93 differentially expressed proteins between RRD and control vitreous humor and revealed altered proteolytic processing of structural and non-structural vitreous components.", "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:41087496"], "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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