Extracellular Vesicles in Corneal Fibrosis/Scarring

Abstract

Communication between cells and the microenvironment is a complex, yet crucial, element in the development and progression of varied physiological and pathological processes. Accumulating evidence in different disease models highlights roles of extracellular vesicles (EVs), either in modulating cell signaling paracrine mechanism(s) or harnessing their therapeutic moiety. Of interest, the human cornea functions as a refractive and transparent barrier that protects the intraocular elements from the external environment. Corneal trauma at the ocular surface may lead to diminished corneal clarity and detrimental effects on visual acuity. The aberrant activation of corneal stromal cells, which leads to myofibroblast differentiation and a disorganized extracellular matrix is a central biological process that may result in corneal fibrosis/scarring. In recent years, understanding the pathological and therapeutic EV mechanism(s) of action in the context of corneal biology has been a topic of increasing interest. In this review, we describe the clinical relevance of corneal fibrosis/scarring and how corneal stromal cells contribute to wound repair and their generation of the stromal haze. Furthermore, we will delve into EV characterization, their subtypes, and the pathological and therapeutic roles they play in corneal scarring/fibrosis.

Doxorubicin-Loaded Extracellular Vesicles Enhance Tumor Cell Death in Retinoblastoma

“…There has been great progress in creating novel methods for different therapeutic approaches, such as 3D bioprinting, hydrogels, and nanoparticles in different diseases [ 56 , 57 , 58 , 59 , 60 ]. Yet, within the past decade, EVs have emerged as a therapeutic tool and potential vehicle for targeted therapy due to their exceptional biocompatibility and physiochemical stability [ 36 , 61 , 62 ]. EVs are nanosized particles with a lipid bilayer that contains a repertoire of intrinsic cargo: mRNA, miRNA, lipids, and proteins derived from the origin cell type [ 63 ].…”

“…EVs as diagnostic modalities and treatment tools are being used for a variety of ocular diseases [ 36 , 37 ]. In patients with uveal melanoma, EVs isolated from serum and other tissues depicted miRNA alterations, aiding in differentiation from healthy controls [ 38 , 39 ].…”

Extracellular vesicles as a new horizon in the diagnosis and treatment of inflammatory eye diseases: A narrative review of the literature

“…Studies demonstrated that EVs are secreted in the wounded cornea and are able to communicate between the corneal stroma and epithelium ( 56 , 95 , 97 ). Also, Han et al.…”

Celastrol Alleviates Corneal Stromal Fibrosis by Inhibiting TGF-β1/Smad2/3-YAP/TAZ Signaling After Descemet Stripping Endothelial Keratoplasty

“…Ultimately, excessive deposition of extracellular matrix (ECM) leads to corneal stromal fibrosis. 6 , 7 Transforming growth factor-β1 (TGF-β1), which induces keratocyte transformation to myofibroblasts, plays a vital role in corneal fibrosis. TGF-β1/Smad2/3 pathway activity causes myofibroblasts to produce large amounts of disordered ECM to generate corneal scarring.…”

“…TGF-β1/Smad2/3 pathway activity causes myofibroblasts to produce large amounts of disordered ECM to generate corneal scarring. 6 , 8 Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ) proteins, which bind to TEAD transcription factors, are essential for profibrotic cues induced by TGF-β in the microenvironment. 9 Elevated YAP/TAZ levels correlate with local tissue fibrosis.…”