Diabetic Retinopathy (DR) is a potentially blinding retinal
disorder that develops through the pathogenesis of diabetes.
The lack of disease predictors implies a poor prognosis with
frequent irreversible retinal damage and vision loss.
Extracellular Vesicles (EVs) present a novel opportunity for
pre-symptomatic disease diagnosis and prognosis, both
severely limited in DR. All biological fluids contain EVs, which
are currently being studied as disease biomarkers. EV proteins
derived from urine have emerged as potential noninvasive
biomarkers. In this study, we isolated EVs from DR retinal
tissue explants and from DR patients urine, and characterized
the vesicles, finding differences in particle number and size.
Next, we performed proteomic analysis on human explanted
DR retinal tissue conditioned media, DR retinal EVs and DR
urinary EVs and compared to normal human retinal tissue,
retinal EVs, and urinary EVs, respectively. Our system biology
analysis of DR tissue and EV expression profiles revealed
biological pathways related to cell-to-cell junctions, vesicle
biology, and degranulation processes. Junction Plakoglobin
(JUP), detected in DR tissue-derived EVs and DR urinary EVs,
but not in controls, was revealed to be a central node in many
identified pathogenic pathways. Proteomic results were
validated by western blot. Urinary EVs obtained from healthy
donors and diabetic patient without DR did not contain JUP.
The absence of JUP in healthy urinary EVs provide the basis
for development of a novel Diabetic Retinopathy biomarker,
potentially facilitating diagnosis.
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