title: Sphere-forming cells from peripheral cornea demonstrate a wound-healing response to injury.
abstract: The cornea is the initial refractive interface of the eye. Its transparency is critical for clear vision and is maintained by stem cells which also act to repair injury inflicted by external insults, such as chemical and thermal burns. Damage to the epithelium compromises its clarity and can reduce or eliminate the stem cell population, diminishing the ability for self-repair. This condition has been termed "limbal stem cell deficiency"; severe cases can lead to corneal blindness. Sphere-forming cells isolated from peripheral cornea are a potential source of stem and progenitor cells for corneal repair. When provided with appropriate substrate, these spheres have the ability to adhere and for cells to migrate outwards akin to that of their natural environment. Direct compression injury and remote scratch injury experiments were conducted on the sphere cells to gauge their wound healing capacity. Measures of proliferation, differentiation, and migration were assessed by immunohistochemical detection of EdU incorporation, α-smooth muscle actin expression and confocal image analysis, respectively. Both modes of injury were observed to draw responses from the spheres indicating wound healing processes. Direct wounding induced a rapid, but transient increase in expression of α-SMA, a marker of corneal myofibroblasts, followed by a proliferative and increasing migratory response. The spheres were observed to respond to remote injury as entire units, with no directional response seen for targeted repair over the scratch injury area. These results give strength to the future use of these peripheral corneal spheres as transplantable units for the regeneration of corneal tissue.
authors.affiliation: Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Stephanie U
authors.initials: SU
authors.lastname: Huang
authors.affiliation: Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Jinny J
authors.initials: JJ
authors.lastname: Yoon
authors.affiliation: Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Salim
authors.initials: S
authors.lastname: Ismail
authors.affiliation: Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: McGhee
authors.affiliation: Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Trevor
authors.initials: T
authors.lastname: Sherwin
mesh_terms: D002454:Cell Differentiation / Q000502:physiology; D003315:Cornea / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D065306:Corneal Injuries / Q000378:metabolism / Q000473:pathology*; D019573:Epithelium, Corneal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D012038:Regeneration / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
keywords: cornea; differentiation; migration; polarity; proliferation; stem cell