June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Proteomic and transcriptomic analysis of human extracellular vesicles as surrogate markers of Age-related Macular Degeneration
Author Affiliations & Notes
  • Timothy Domashevich
    Department of Ophthalmology, CellSightOcular Stem Cell and Regeneration Program, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, United States
  • Anthony Saviola
    Biochemistry & Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • Hector Peinado
    Centro Nacional de Investigaciones Oncologicas, Madrid, Madrid, Spain
  • Naresh Mandava
    Sue Anschutz-Rodgers Eye Center, Department of Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Stephen Redenti
    Biology, Lehman College of CUNY Division of Natural and Social Science, Bronx, New York, United States
  • Anne M Lynch
    Sue Anschutz-Rodgers Eye Center, Department of Ophthalmology, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Miguel Flores-Bellver
    Department of Ophthalmology, CellSightOcular Stem Cell and Regeneration Program, Sue Anschutz-Rodgers Eye Center, University of Colorado, School of Medicine, Aurora, Colorado, United States
  • Footnotes
    Commercial Relationships   Timothy Domashevich None; Anthony Saviola None; Hector Peinado None; Naresh Mandava None; Stephen Redenti None; Anne Lynch None; Miguel Flores-Bellver None
  • Footnotes
    Support  CellSight Development Fund, Research to Prevent Blindness (RPB), The Bert M. Glaser, MD Award for Innovative Research in Retina
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2739. doi:
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    • Get Citation

      Timothy Domashevich, Anthony Saviola, Hector Peinado, Naresh Mandava, Stephen Redenti, Anne M Lynch, Miguel Flores-Bellver; Proteomic and transcriptomic analysis of human extracellular vesicles as surrogate markers of Age-related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2739.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment in the elderly. Emerging evidence suggests extracellular vesicles (EVs), such as exosomes and microvesicles, participate in the pathogenesis of AMD. EVs released by all cells contain lipids, proteins, and nucleic acids. The cargo of EVs is related to the nature and physiology of their cell of origin and any change in cell homeostasis might modify their molecular composition. EVs can travel through different biofluids (i.e., blood, tears, saliva). The purpose of this study was to investigate the cargo contained in plasma-derived EVs in patients with different phenotypes of AMD and to specifically characterize the proteome and transcriptome cargo which has not been previously described

Methods : 40 patients enrolled in the University of Colorado AMD Registry were used in the study. AMD phenotypes were determined using multimodal imaging. Plasma from 10 control (CT), 10 intermediate AMD (iAMD), 10 Geographic Atrophy (GA), and 10 Neovascular (NV) AMD patients was used to study EVs. We isolated EVs using size exclusion chromatography. We characterized vesicle morphology, molecular composition, size, and distribution by electron microscopy (TEM), immunoblotting, and Nanosight (NTA). Finally, EV cargo was characterized by proteomic and transcriptomic analysis

Results : We observed typical rounded membrane vesicles within a size range of 30–170 nm. The physical characteristics of the vesicle preparations and their biochemical composition (presence of Syntenin, and absence of GM130) confirmed that they fulfilled the criteria for EVs. EVs isolated from the plasma of patients with intermediate AMD and late AMD (NV and GA) had different protein and RNA profiles than those of CT group. Furthermore, proteomic profiling of plasma-derived EV cargo revealed that EVs were enriched in proteins related to the complement and the immune system

Conclusions : This study represents the first description of the transcriptomic and proteomic profile from EV released in plasma from AMD patients. Our results are aligned with the findings of other investigators who have shown that that EVs reflect intracellular changes that occur in response to pathological conditions. Assessing EV biomarkers in circulating extracellular vesicles could be a powerful non-invasive approach to monitor AMD disease progression

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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