Altered pattern of proteolysis in rhegmatogenous retinal detachment by mining of N-termini datasets from vitreous humor proteome
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".