Corneal stromal wound healing in refractive surgery: the role of myofibroblasts.
While laser and incisional refractive surgery offer the promise to correct visual refractive errors permanently and predictably, variability and complications continue to hinder wide-spread acceptance. To explain variations, recent studies have focused on the role of corneal wound healing in modulating refractive outcomes. As our understanding of the corneal response to refractive surgery broadens, it has become apparent that the response of one cell, the corneal stromal keratocyte, plays a pivotal role in defining the results of refractive surgery. Studies reviewed herein demonstrate that injury-induced activation and transformation of keratocytes to myofibroblasts control the deposition and organization of extracellular matrix in corneal wounds. Myofibroblasts establish an interconnected meshwork of cells and extracellular matrix that deposits new matrix and contracts wounds using a novel and unexpected "shoe-string-like" mechanism. Transformation of keratocytes to myofibroblasts is induced in culture by transforming growth factor beta (TGFbeta) and blocked in vivo by antibodies to TGFbeta. Overall, myofibroblast appearance in corneal wounds is associated with wound contraction and regression following incisional keratotomy and the development of "haze" or increased scattered light following laser photorefractive keratectomy (PRK). By contrast, absence of myofibroblasts is associated with continued widening of wound gape and progressive corneal flattening after incisional procedures. Based on these studies, we have arrived at the inescapable conclusion that a better understanding of the cellular and molecular biology of this one cell is required if refractive surgery is ever to achieve predictable and safe refractive results.
Jester
J V
JV
Department of Ophthalmology, The University of Texas Southwestern Medical Center at Dallas, 75235-9057, USA.
Petroll
W M
WM
Cavanagh
H D
HD
D000818:Animals; D003319:Corneal Stroma / Q000503:physiopathology*; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D009130:Muscle, Smooth / Q000473:pathology / Q000503:physiopathology*; D012030:Refractive Errors / Q000503:physiopathology; D054140:Refractive Surgical Procedures; D014945:Wound Healing / Q000502:physiology*