Potential role of corneal epithelial cell-derived exosomes in corneal wound healing and neovascularization.
Specific factors from the corneal epithelium underlying the stimulation of stromal fibrosis and myofibroblast formation in corneal wound healing have not been fully elucidated. Given that exosomes are known to transfer bioactive molecules among cells and play crucial roles in wound healing, angiogenesis, and cancer, we hypothesized that corneal epithelial cell-derived exosomes may gain access to the underlying stromal fibroblasts upon disruption of the epithelial basement membrane and that they induce signaling events essential for corneal wound healing. In the present study, exosome-like vesicles were observed between corneal epithelial cells and the stroma during wound healing after corneal epithelial debridement. These vesicles were also found in the stroma following anterior stromal keratectomy, in which surgical removal of the epithelium, basement membrane, and anterior stroma was performed. Exosomes secreted by mouse corneal epithelial cells were found to fuse to keratocytes in vitro and to induce myofibroblast transformation. In addition, epithelial cell-derived exosomes induced endothelial cell proliferation and ex vivo aortic ring sprouting. Our results indicate that epithelial cell-derived exosomes mediate communication between corneal epithelial cells and corneal keratocytes as well as vascular endothelial cells. These findings demonstrate that epithelial-derived exosomes may be involved in corneal wound healing and neovascularization, and thus, may serve as targets for potential therapeutic interventions.
Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
Kyu-Yeon
KY
Han
Schepens Eye Research Institute/MEE, Boston, Massachusetts, United States.
Jennifer A
JA
Tran
Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
Jin-Hong
JH
Chang
Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.
Dimitri T
DT
Azar
Schepens Eye Research Institute/MEE, Boston, Massachusetts, United States.|Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
James D
JD
Zieske
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D019573:Epithelium, Corneal / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D055354:Exosomes / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008561:Membrane Fusion; D008810:Mice, Inbred C57BL; D058628:Myofibroblasts / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic; D011817:Rabbits; D051381:Rats; D060149:Tetraspanin 30 / Q000378:metabolism; D014945:Wound Healing
D060149:Tetraspanin 30