Liquid biopsy of vitreous reveals an abundant vesicle population consistent with the size and morphology of exosomes

Yuanjun Zhao, Sarah R. Weber, Joshua Lease, Mariano Russo, Christopher Siedlecki, Lichong Xu, Han Chen, Weiwei Wang, Michael Ford, Rafael Simó, Jeffrey Sundstrom

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Purpose: To investigate the molecular components of the vitreous in order to better understand retinal physiology and disease. Methods: Vitreous was acquired from patients undergoing vitrectomy for macular hole and/or epiretinal membrane, postmortem donors, and C57BL/6J mice. Unbiased proteomic analysis was performed via electrospray ionization tandem mass spectrometry (MS/MS). Gene ontology analysis was performed and results were confirmed with transmission electron microscopy, atomic force microscopy, and nanoparticle tracking analysis (NTA). Results: Proteomic analysis of vitreous obtained prior to vitrectomy identified a total of 1121 unique proteins. Gene ontology analysis revealed that 62.6% of the vitreous proteins were associated with the gene ontology term ‘‘extracellular exosome.’’ Ultrastructural analyses, Western blot, and NTA confirmed the presence of an abundant population of vesicles consistent with the size and morphology of exosomes in human vitreous. The concentrations of vitreous vesicles in vitrectomy patients, postmortem donors, and mice were 1.3, 35, and 9 billion/mL, respectively. Conclusions: Overall, these data strongly suggest that information-rich exosomes are a major constituent of the vitreous. The abundance of these vesicles and the presence of retinal proteins imply a dynamic interaction between the vitreous and retina. Future studies will be required to identify the cellular origin of vitreal exosomes as well as to assess the potential role of these vesicles in retinal disease and treatment. Translational Relevance: The identification of vitreous exosomes lays the groundwork for a transformed understanding of pathophysiology and treatment mechanisms in retinal disease, and further validates the use of vitreous as a proximal biofluid of the retina.

Original languageEnglish (US)
Article number6
JournalTranslational Vision Science and Technology
Volume7
Issue number3
DOIs
StatePublished - May 1 2018

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Exosomes
Biopsy
Ontology
Genes
Retinal Diseases
Gene Ontology
Proteins
Vitrectomy
Liquids
Population
Nanoparticles
Electrospray ionization
Proteomics
Physiology
Retina
Mass spectrometry
Tissue Donors
Atomic force microscopy
Epiretinal Membrane
Retinal Perforations

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Ophthalmology

Cite this

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title = "Liquid biopsy of vitreous reveals an abundant vesicle population consistent with the size and morphology of exosomes",
abstract = "Purpose: To investigate the molecular components of the vitreous in order to better understand retinal physiology and disease. Methods: Vitreous was acquired from patients undergoing vitrectomy for macular hole and/or epiretinal membrane, postmortem donors, and C57BL/6J mice. Unbiased proteomic analysis was performed via electrospray ionization tandem mass spectrometry (MS/MS). Gene ontology analysis was performed and results were confirmed with transmission electron microscopy, atomic force microscopy, and nanoparticle tracking analysis (NTA). Results: Proteomic analysis of vitreous obtained prior to vitrectomy identified a total of 1121 unique proteins. Gene ontology analysis revealed that 62.6{\%} of the vitreous proteins were associated with the gene ontology term ‘‘extracellular exosome.’’ Ultrastructural analyses, Western blot, and NTA confirmed the presence of an abundant population of vesicles consistent with the size and morphology of exosomes in human vitreous. The concentrations of vitreous vesicles in vitrectomy patients, postmortem donors, and mice were 1.3, 35, and 9 billion/mL, respectively. Conclusions: Overall, these data strongly suggest that information-rich exosomes are a major constituent of the vitreous. The abundance of these vesicles and the presence of retinal proteins imply a dynamic interaction between the vitreous and retina. Future studies will be required to identify the cellular origin of vitreal exosomes as well as to assess the potential role of these vesicles in retinal disease and treatment. Translational Relevance: The identification of vitreous exosomes lays the groundwork for a transformed understanding of pathophysiology and treatment mechanisms in retinal disease, and further validates the use of vitreous as a proximal biofluid of the retina.",
author = "Yuanjun Zhao and Weber, {Sarah R.} and Joshua Lease and Mariano Russo and Christopher Siedlecki and Lichong Xu and Han Chen and Weiwei Wang and Michael Ford and Rafael Sim{\'o} and Jeffrey Sundstrom",
year = "2018",
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Liquid biopsy of vitreous reveals an abundant vesicle population consistent with the size and morphology of exosomes. / Zhao, Yuanjun; Weber, Sarah R.; Lease, Joshua; Russo, Mariano; Siedlecki, Christopher; Xu, Lichong; Chen, Han; Wang, Weiwei; Ford, Michael; Simó, Rafael; Sundstrom, Jeffrey.

In: Translational Vision Science and Technology, Vol. 7, No. 3, 6, 01.05.2018.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Liquid biopsy of vitreous reveals an abundant vesicle population consistent with the size and morphology of exosomes

AU - Zhao, Yuanjun

AU - Weber, Sarah R.

AU - Lease, Joshua

AU - Russo, Mariano

AU - Siedlecki, Christopher

AU - Xu, Lichong

AU - Chen, Han

AU - Wang, Weiwei

AU - Ford, Michael

AU - Simó, Rafael

AU - Sundstrom, Jeffrey

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Purpose: To investigate the molecular components of the vitreous in order to better understand retinal physiology and disease. Methods: Vitreous was acquired from patients undergoing vitrectomy for macular hole and/or epiretinal membrane, postmortem donors, and C57BL/6J mice. Unbiased proteomic analysis was performed via electrospray ionization tandem mass spectrometry (MS/MS). Gene ontology analysis was performed and results were confirmed with transmission electron microscopy, atomic force microscopy, and nanoparticle tracking analysis (NTA). Results: Proteomic analysis of vitreous obtained prior to vitrectomy identified a total of 1121 unique proteins. Gene ontology analysis revealed that 62.6% of the vitreous proteins were associated with the gene ontology term ‘‘extracellular exosome.’’ Ultrastructural analyses, Western blot, and NTA confirmed the presence of an abundant population of vesicles consistent with the size and morphology of exosomes in human vitreous. The concentrations of vitreous vesicles in vitrectomy patients, postmortem donors, and mice were 1.3, 35, and 9 billion/mL, respectively. Conclusions: Overall, these data strongly suggest that information-rich exosomes are a major constituent of the vitreous. The abundance of these vesicles and the presence of retinal proteins imply a dynamic interaction between the vitreous and retina. Future studies will be required to identify the cellular origin of vitreal exosomes as well as to assess the potential role of these vesicles in retinal disease and treatment. Translational Relevance: The identification of vitreous exosomes lays the groundwork for a transformed understanding of pathophysiology and treatment mechanisms in retinal disease, and further validates the use of vitreous as a proximal biofluid of the retina.

AB - Purpose: To investigate the molecular components of the vitreous in order to better understand retinal physiology and disease. Methods: Vitreous was acquired from patients undergoing vitrectomy for macular hole and/or epiretinal membrane, postmortem donors, and C57BL/6J mice. Unbiased proteomic analysis was performed via electrospray ionization tandem mass spectrometry (MS/MS). Gene ontology analysis was performed and results were confirmed with transmission electron microscopy, atomic force microscopy, and nanoparticle tracking analysis (NTA). Results: Proteomic analysis of vitreous obtained prior to vitrectomy identified a total of 1121 unique proteins. Gene ontology analysis revealed that 62.6% of the vitreous proteins were associated with the gene ontology term ‘‘extracellular exosome.’’ Ultrastructural analyses, Western blot, and NTA confirmed the presence of an abundant population of vesicles consistent with the size and morphology of exosomes in human vitreous. The concentrations of vitreous vesicles in vitrectomy patients, postmortem donors, and mice were 1.3, 35, and 9 billion/mL, respectively. Conclusions: Overall, these data strongly suggest that information-rich exosomes are a major constituent of the vitreous. The abundance of these vesicles and the presence of retinal proteins imply a dynamic interaction between the vitreous and retina. Future studies will be required to identify the cellular origin of vitreal exosomes as well as to assess the potential role of these vesicles in retinal disease and treatment. Translational Relevance: The identification of vitreous exosomes lays the groundwork for a transformed understanding of pathophysiology and treatment mechanisms in retinal disease, and further validates the use of vitreous as a proximal biofluid of the retina.

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