ITRAQ Quantitative Proteomic Analysis of Vitreous from Patients with Retinal Detachment.

Fátima Santos,Alberto Paradela,João Castro E Sousa,Cândida Tomaz,Ana Rocha,Luís Passarinha,Leonor Gaspar,Sergio Ciordia

doi:10.3390/ijms19041157

Abstract

Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition characterized by a physical separation between neurosensory retina and retinal pigment epithelium. Quantitative proteomics can help to understand the changes that occur at the cellular level during RRD, providing additional information about the molecular mechanisms underlying its pathogenesis. In the present study, iTRAQ labeling was combined with two-dimensional LC-ESI-MS/MS to find expression changes in the proteome of vitreous from patients with RRD when compared to control samples. A total of 150 proteins were found differentially expressed in the vitreous of patients with RRD, including 96 overexpressed and 54 underexpressed. Several overexpressed proteins, several such as glycolytic enzymes (fructose-bisphosphate aldolase A, gamma-enolase, and phosphoglycerate kinase 1), glucose transporters (GLUT-1), growth factors (metalloproteinase inhibitor 1), and serine protease inhibitors (plasminogen activator inhibitor 1) are regulated by HIF-1, which suggests that HIF-1 signaling pathway can be triggered in response to RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Also, the accumulation of photoreceptor proteins, including phosducin, rhodopsin, and s-arrestin, and vimentin in vitreous may indicate that photoreceptor degeneration occurs in RRD. Nevertheless, the differentially expressed proteins found in this study suggest that different mechanisms are activated after RRD to promote the survival of retinal cells through complex cellular responses.

Highlights

Retinal Detachment (RD) is a potentially blinding disease characterized by a physical separation between the neurosensory retina (NSR) and the underlying retinal pigment epithelium (RPE) [1,2]
Many proteins involved in acute inflammatory response and in complement and coagulation cascades were found underexpressed in Rhegmatogenous retinal detachment (RRD)
A total of 1030 proteins were identified using isobaric tags for relative and absolute quantitation (iTRAQ) labelling combined with two-dimensional LC-ESI-MS/MS, and 150 proteins were found differentially expressed between RRD and MEM control (96 overexpressed and 54 underexpressed proteins)

Summary

Introduction

Retinal Detachment (RD) is a potentially blinding disease characterized by a physical separation between the neurosensory retina (NSR) and the underlying retinal pigment epithelium (RPE) [1,2]. Modifications in adhesion between the NSR and RPE and the degradation of interphotoreceptor matrix glue can be involved in the onset of RD [3,4]. Risk factors such as age, the level of oxygenation, and other ocular diseases (e.g., myopia, vitreoretinal degeneration) contribute to reducing the retinal adhesion, and to the development of RD [3,4,5]. Rhegmatogenous retinal detachment (RRD) may be triggered by vitreous syneresis, a liquefaction of gel caused by age or by trauma, which reduces the vitreoretinal adhesion and results in deflation and relaxation of the collagen network and in the accumulation of vitreous fluid in subretinal space [3,4,7]. Vitreous falls upon itself causing the physical separation between the NSR and the RPE of the retina, leading to severe and permanent loss of vision [4,5,7]

Methods

Results

Discussion

Conclusion