Putative Biomarkers in Tears for Diabetic Retinopathy Diagnosis

Overview

Journal Front Med (Lausanne)

Specialty General Medicine

Date 2022 Jun 13

PMID 35692536

Authors

Madania Amorim

Beatriz Martins

Francisco Caramelo

Conceicao Goncalves

Grimalde Trindade

Jorge Simao

Patricia Barreto

Ines Marques

Ermelindo Carreira Leal

Eugenia Carvalho

Flavio Reis

Teresa Ribeiro-Rodrigues

Henrique Girao

Paulo Rodrigues-Santos

Claudia Farinha

Antonio Francisco Ambrosio

Rufino Silva

Rosa Fernandes

Affiliations

Soon will be listed here.

Abstract

Purpose: Tear fluid biomarkers may offer a non-invasive strategy for detecting diabetic patients with increased risk of developing diabetic retinopathy (DR) or increased disease progression, thus helping both improving diagnostic accuracy and understanding the pathophysiology of the disease. Here, we assessed the tear fluid of nondiabetic individuals, diabetic patients with no DR, and diabetic patients with nonproliferative DR (NPDR) or with proliferative DR (PDR) to find putative biomarkers for the diagnosis and staging of DR.

Methods: Tear fluid samples were collected using Schirmer test strips from a cohort with 12 controls and 54 Type 2 Diabetes (T2D) patients, and then analyzed using mass spectrometry (MS)-based shotgun proteomics and bead-based multiplex assay. Tear fluid-derived small extracellular vesicles (EVs) were analyzed by transmission electron microscopy, Western Blotting, and nano tracking.

Results: Proteomics analysis revealed that among the 682 reliably quantified proteins in tear fluid, 42 and 26 were differentially expressed in NPDR and PDR, respectively, comparing to the control group. Data are available via ProteomeXchange with identifier PXD033101. By multicomparison analyses, we also found significant changes in 32 proteins. Gene ontology (GO) annotations showed that most of these proteins are associated with oxidative stress and small EVs. Indeed, we also found that tear fluid is particularly enriched in small EVs. T2D patients with NPDR have higher IL-2/-5/-18, TNF, MMP-2/-3/-9 concentrations than the controls. In the PDR group, IL-5/-18 and MMP-3/-9 concentrations were significantly higher, whereas IL-13 was lower, compared to the controls.

Conclusions: Overall, the results show alterations in tear fluid proteins profile in diabetic patients with retinopathy. Promising candidate biomarkers identified need to be validated in a large sample cohort.

Citing Articles

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