Dataset Information

ALTERED PATTERN OF PROTEOLYSIS OF EXTRACELLULAR PROTEINS IN RHEGMATOGENOUS RETINAL DETACHMENT BY MINING OF TRYPTIC AND N-TERMINI DATASETS FROM VITREOUS HUMOR PROTEOME

ABSTRACT: Retinal detachment is a severe eye condition characterized by the detachment of the neurosensory retina from the retinal pigment epithelium and caused by retinal tears. Pars plana vitrectomy is the elective surgical procedure during which vitreous humor, a fluid which shapes the eye globe and supports mechanically the adherence of the retina to the posterior chamber of the eye, is collected. Therefore, profiling of the vitreous humor proteome of subjects diagnosed with retinal detachment is supposed to provide molecular evidence on the pathobiology of the disease and on its secondary complications, such as proliferative vitreo-retinopathy, which predispose to recurrent RD (observed in 20% of cases), a sight threatening condition. Herein, we investigated the perturbations of vitreous proteome between subjects affected by primary retinal detachment and controls by shot-gun proteomics approaches. Proteomic datasets were first analyzed and searched for global proteome changes. Thereafter, starting from the assumption that the disease could be sustained by altered proteolytic processing of structural and non-structural elements of the VH, mining of N- and C-termini was performed to uncover endogenous proteolytic events underscoring the disease condition. The search retrieved evidence of a wide repertoire of either previously characterized or uncharacterized proteolytic events. Most notably, comparison of the N- and C-termini landscape between experimental groups highlighted robust alterations in the repertoire of cleaved proteins. Further strengthened by immunoblotting studies on a select panel of proteins, the data envisage that retinal detachment is promoted or characterized, as a secondary process, by proteolytic-based alterations of structural and non-structural components involved in the regulation of immune process, proteases inhibition and most notably, angiogenesis.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Vitreous Humor

DISEASE(S): Retinal Detachment

SUBMITTER: Diego Sbardella

LAB HEAD: M.D. Ph.D. Diego Sbardella

PROVIDER: PXD057155 | Pride | 2025-10-20

REPOSITORIES: Pride

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Publications

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

Zingale Gabriele Antonio GA Giammaria Sara S Pandino Irene I Placentino Luca L Ripandelli Guido G Tundo Grazia Raffaella GR Grasso Giuseppe G Bocedi Alessio A Bell Peter A PA Rossi Tommaso T Sbardella Diego D

Scientific reports 20251014 1

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 di ...[more]

PMID: 41087496

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Project description:The vitreous humor can provide important information about physiological and pathophysiological processes within the eye, particularly concerning the retina. Despite the widespread prevalence of various vitreoretinal diseases, that can ultimately lead to blindness, there is not a clear understanding of many molecular processes underlying these conditions. Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults in U.S. and developed world. It can result in macular edema and tractional retinal detachment (TRD). Hyperglycemia can induce damage to retinal cells and capillary closure, leading to retinal ischemia and elevated levels of nitric oxide (NO). This, in turn, increases the activity of protein kinase C and the levels of different growth factors, including vascular endothelial growth factor (VEGF). These events can stimulate the development of new blood vessels from existing matured vessels, which are subsequently encompassed by glial cells and fibrous proliferation, potentially leading to TRD. Rhegmatogenous retinal detachment (RD) is the separation of neuroretinal layers from the retinal pigment epithelium (RPE), induced by a break in the neuroretina that allows the influx of liquefied vitreous. In the detached retina outer layers become ischemic and photoreceptors undergo cell death mainly by apoptosis. Moreover, 3–4 days after retinal detachment, a peak of proliferation of non-neuronal cells, such as astrocytes, endothelial cells, pericytes, and microglia, can be observed. A possible complication of rhegmatogenous retinal detachment is proliferative vitreoretinopathy (PVR), a condition defined by the growth and contraction of cellular membranes within the vitreous cavity. Fibroblast or fibrocyte cells have been detected in epiretinal membranes in PVR, and the origin of these cells is debated. Different authors have suggested that they could be transformed RPE cells or metaplastic vascular endothelial cells, glial cells, macrophages, or hyalocytes. Macular pucker is a condition defined by an epiretinal membrane described as a semi-translucent avascular membrane over the internal limiting membrane (ILM) on the surface of the retina. It can be idiopathic or secondary to various conditions, such as trauma, intraocular inflammation, etc. The initial event that can induce an idiopathic pucker is posterior vitreous detachment (PVD), which can cause dehiscence in the internal limiting membrane. Through this opening, microglial cells move to the preretinal surface, where they can interact with hyalocytes and laminocytes. Subsequent transdifferentiation to fibroblast-like cells leads to the development of an epiretinal membrane.

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