Extracellular Vesicles in the Cornea: Insights from Other Tissues

Abstract

Extracellular vesicles (EVs) are phospholipid bilayer-bound particles secreted by cells that have been found to be important in mediating cell-cell communication, signal transduction, and extracellular matrix remodeling. Their role in both physiological and pathological processes has been established in different tissues throughout the human body. The human cornea functions as a transparent and refractive barrier that protects the intraocular elements from the external environment. Injury, infection, or disease may cause the loss of corneal clarity by altering extracellular matrix organization within the stroma that may lead to detrimental effects on visual acuity. Over the years, numerous studies have identified many of the growth factors (e.g., transforming growth factor-β1, thrombospondin-1, and platelet-derived growth factor) important in corneal wound healing and scarring. However, the functional role of bound factors encapsulated in EVs in the context of corneal biology is less defined. In this review, we describe the discovery and characterization of EVs in the cornea. We focus on EV-matrix interactions, potential functions during corneal wound healing, and the bioactivity of mesenchymal stem cell-derived EVs. We also discuss the development of EVs as stable, drug-loaded therapeutics for ocular applications.

Extracellular Vesicles Secreted by Corneal Myofibroblasts Promote Corneal Epithelial Cell Migration

“…Following the isolation of HCK-, HCF-, and HCM-EVs, there are many normalization strategies varying between cell number, lipid concentration, or particle counts, but we kept a constant protein concentration, akin to previous corneal-related studies [ 11 , 16 , 41 ], as this eliminates any bias towards overdosing EV towards a different metric. Hence, the corneal stromal EVs used for the proteomic analysis and functional experiences were normalized by protein concentration and should reflect the differences in EV phenotype.…”

“…To date, our understanding of stromal cells, such as adipocytes, fibrocytes, fibroblasts, and mesenchymal stem cells (MSCs), along with their secreted EVs, has been reported in studies that mediate disease-exacerbating changes in asthma [ 17 ], cancer [ 18 , 19 , 20 , 21 , 22 ], fibrosis [ 23 , 24 , 25 ], and cardiovascular diseases [ 26 , 27 , 28 ], but also show the therapeutic action of MSC-EVs by targeting different tissues, including the lungs, placenta, and thymus [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 ]. By focusing on the cornea, studies have investigated how corneal MSC-EVs can improve corneal epithelial wound healing, reduce corneal epithelial defects, and promote scarless stromal recovery post-corneal injury in vivo [ 38 , 39 , 40 , 41 ]. These studies revealed a novel application of EVs as therapeutic carriers of cargo that promotes corneal tissue regeneration.…”

Bone Marrow Mesenchymal Stem Cells and Their Derived Extracellular Vesicles Attenuate Non-Alcoholic Steatohepatitis-Induced Cardiotoxicity via Modulating Cardiac Mechanisms

“…Among these are bone-marrow-derived MSCs (BM-MSCs), whose potential therapeutic effects in CVDs were theoretically translated from their wide differentiation capacity [ 20 ]. Besides, recent studies revealed that MSCs reparative effects could occur through paracrine manner as well [ 21 , 22 , 23 , 24 , 25 ]. Being one of the best known sources of progenitor cells, BM-MSCs are successfully capable of differentiation into cardiomyocyte, and thus, several reports point to their importance as a reliable therapeutic approach for several CVDs [ 26 , 27 , 28 ].…”

The Role of Exosome and the ESCRT Pathway on Enveloped Virus Infection

“…Consequently, certain proteins, including classic exosomal markers, are present and may be used as exosomes markers following the minimum guidelines set by the International Society of Extracellular Vesicles (ISEV) [10]. An array of exosomes markers such as the tetraspanin proteins (CD9, CD63, and CD81), flotillin-1/-2, ESCRT-related (ALIX and TSG101), RABs, SNAREs, and others have been reported in different disease models [11][12][13][14][15][16][17][18]. However, with a particular focus on budding and infection of viruses, recent studies showed that nucleic acids, proteins, and even virions of enveloped viruses can be wrapped into the exosomes and transmitted between cells by the "free ride" of exosomes.…”