Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior

Exosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification...

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Main Authors: Víctor Lozano, Carla Martín, Noelia Blanco, Ignacio Alcalde, Luis Fernandez-Vega Cueto, Jesús Merayo-Lloves, Luis M. Quirós
Format: Article
Language:English
Published: MDPI AG 2022-09-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/10/10/2348
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author Víctor Lozano
Carla Martín
Noelia Blanco
Ignacio Alcalde
Luis Fernandez-Vega Cueto
Jesús Merayo-Lloves
Luis M. Quirós
author_facet Víctor Lozano
Carla Martín
Noelia Blanco
Ignacio Alcalde
Luis Fernandez-Vega Cueto
Jesús Merayo-Lloves
Luis M. Quirós
author_sort Víctor Lozano
collection DOAJ
description Exosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification of 14 new proteins with altered expression, related to molecules previously associated with the pathology. miRNA analysis detected 16 altered species, including miR-184, responsible for familial severe keratoconus. The prediction of its potential biological targets identified 1121 genes, including some related to this pathology. Exosomes produced by keratoconic cells induced a marked increase in the migration of stromal cells and corneal epithelium, while those produced by healthy cells had no effect on stromal cells. Both types of nanovesicles reduced the proliferation of stromal and corneal cells, but those produced by healthy cells had less effect. Exosomes produced by healthy cells had concentration-dependent effects on the transcription of genes encoding proteoglycans by keratoconus cells, with a relative normalization observed at concentrations of 240 µg/mL. These results show the alteration of stromal exosomes in keratoconus and suggest an influence on the development of the pathology, although the use of healthy exosomes could also have therapeutic potential.
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spelling doaj.art-d9019921d85f46f1817aa6fa2c6be46c2023-11-23T23:01:40ZengMDPI AGBiomedicines2227-90592022-09-011010234810.3390/biomedicines10102348Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular BehaviorVíctor Lozano0Carla Martín1Noelia Blanco2Ignacio Alcalde3Luis Fernandez-Vega Cueto4Jesús Merayo-Lloves5Luis M. Quirós6Department of Functional Biology, University of Oviedo, 33006 Oviedo, SpainDepartment of Functional Biology, University of Oviedo, 33006 Oviedo, SpainDepartment of Functional Biology, University of Oviedo, 33006 Oviedo, SpainInstituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, University of Oviedo, 33012 Oviedo, SpainInstituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, University of Oviedo, 33012 Oviedo, SpainInstituto Universitario Fernández-Vega, Fundación de Investigación Oftalmológica, University of Oviedo, 33012 Oviedo, SpainDepartment of Functional Biology, University of Oviedo, 33006 Oviedo, SpainExosomes have been related to various disorders, but their study in relation to ocular pathologies has been limited. In this article, we analyze exosomes produced by corneal stromal cells from healthy individuals and from patients with keratoconus. The proteomic study allowed for the identification of 14 new proteins with altered expression, related to molecules previously associated with the pathology. miRNA analysis detected 16 altered species, including miR-184, responsible for familial severe keratoconus. The prediction of its potential biological targets identified 1121 genes, including some related to this pathology. Exosomes produced by keratoconic cells induced a marked increase in the migration of stromal cells and corneal epithelium, while those produced by healthy cells had no effect on stromal cells. Both types of nanovesicles reduced the proliferation of stromal and corneal cells, but those produced by healthy cells had less effect. Exosomes produced by healthy cells had concentration-dependent effects on the transcription of genes encoding proteoglycans by keratoconus cells, with a relative normalization observed at concentrations of 240 µg/mL. These results show the alteration of stromal exosomes in keratoconus and suggest an influence on the development of the pathology, although the use of healthy exosomes could also have therapeutic potential.https://www.mdpi.com/2227-9059/10/10/2348exosomeskeratoconuscorneal stromaproteomicsmiRNA
spellingShingle Víctor Lozano
Carla Martín
Noelia Blanco
Ignacio Alcalde
Luis Fernandez-Vega Cueto
Jesús Merayo-Lloves
Luis M. Quirós
Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior
Biomedicines
exosomes
keratoconus
corneal stroma
proteomics
miRNA
title Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior
title_full Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior
title_fullStr Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior
title_full_unstemmed Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior
title_short Exosomes Released by Corneal Stromal Cells Show Molecular Alterations in Keratoconus Patients and Induce Different Cellular Behavior
title_sort exosomes released by corneal stromal cells show molecular alterations in keratoconus patients and induce different cellular behavior
topic exosomes
keratoconus
corneal stroma
proteomics
miRNA
url https://www.mdpi.com/2227-9059/10/10/2348
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