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Extracellular vesicles of human diabetic retinopathy retinal tissue and urine of diabetic retinopathy patients analyzed using mass spectrometry

ABSTRACT: Diabetic Retinopathy (DR) is a potentially blinding retinal disorder which develops through the pathogenesis of diabetes. Extracellular Vesicles (EVs) provide a novel biomarker for pre-symptomatic disease diagnosis and prognosis. Proteomic analysis was performed on explanted DR retinal tissue, DR retinal EVs and DR urinary EVs. DR samples were compared to normal retinal tissue, retinal EVs and urinary EVs, respectively

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Urine

DISEASE(S): Diabetic Retinopathy

SUBMITTER: Soren Heissel

LAB HEAD: Stephen Redenti

PROVIDER: PXD034626 | Pride | 2022-12-31

REPOSITORIES: Pride

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Project description:The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the enzyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Background: Synaptic dysfunction and neuronal damage have been extensively associated with diabetic retinopathy (DR). Our group evidenced that chronic hyperglycemia reduces the retinal expression of presynaptic proteins, which are crucial for a proper synaptic function. The aim of the study was to explore the effect of topically administered sitagliptin, an inhibitor of the en-zyme dipeptidyl peptidase-4, on the retinal expression patterns of an experimental model of DR. Methods: Transcriptome analysis was performed comparing the retinas of 10 diabetic (db/db) mice randomly treated with sitagliptin eye drops (10 mg/mL) twice daily, and the reti-nas of 10 additional db/db mice that received vehicle eye drops. 10 non diabetic mice (db/+) were used as control group. Gene Ontology (GO) and Reactome databases were used to assess the Gene Set Enrichment Analysis (GSEA) in order to explore the most enriched biological pathways among groups. The most differentiated genes of these pathways were validated through quantitative RT-PCR. Results: Transcriptome analysis revealed that sitagliptin eye drops have a significant effect on retinal expression patterns and that neurotransmission was the most enriched biological process. Our study evidenced enriched pathways that contain genes involved in membrane trafficking, transmission across chemical synapses, vesi-cle-mediated transport, neurotransmitter receptors and postsynaptic signal transmission with negative regulation of signaling as a consequence of neuroprotector treatment with sitagliptin. This improves the modulation of macromolecule biosynthetic process with positive regulation of cell communication which provides beneficial effects for neuronal metabolism. Conclu-sions: This study suggests that topical administration of sitagliptin ameliorates the abnormali-ties on presynaptic and postsynaptic signal transmission during experimental DR, and that this improvement is one of the main mechanisms behind the previously demonstrated beneficial effects.

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Extracellular vesicles of human diabetic retinopathy retinal tissue and urine of diabetic retinopathy patients analyzed using mass spectrometry

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