Myofibroblast transdifferentiation: The dark force in ocular wound healing and fibrosis

Prog Retin Eye Res. 2017 Sep;60:44-65. doi: 10.1016/j.preteyeres.2017.08.001. Epub 2017 Aug 12.


Wound healing is one of the most complex biological processes to occur in life. Repair of tissue following injury involves dynamic interactions between multiple cell types, growth factors, inflammatory mediators and components of the extracellular matrix (ECM). Aberrant and uncontrolled wound healing leads to a non-functional mass of fibrotic tissue. In the eye, fibrotic disease disrupts the normally transparent ocular tissues resulting in irreversible loss of vision. A common feature in fibrotic eye disease is the transdifferentiation of cells into myofibroblasts that can occur through a process known as epithelial-mesenchymal transition (EMT). Myofibroblasts rapidly produce excessive amounts of ECM and exert tractional forces across the ECM, resulting in the distortion of tissue architecture. Transforming growth factor-beta (TGFβ) plays a major role in myofibroblast transdifferentiation and has been implicated in numerous fibrotic eye diseases including corneal opacification, pterygium, anterior subcapsular cataract, posterior capsular opacification, proliferative vitreoretinopathy, fibrovascular membrane formation associated with proliferative diabetic retinopathy, submacular fibrosis, glaucoma and orbital fibrosis. This review serves to introduce the pathological functions of the myofibroblast in fibrotic eye disease. We also highlight recent developments in elucidating the multiple signaling pathways involved in fibrogenesis that may be exploited in the development of novel anti-fibrotic therapies to reduce ocular morbidity due to scarring.

Keywords: Epithelial-mesenchymal transition (EMT); Fibrosis; Myofibroblast; Ocular; Transforming growth factor-beta (TGFβ); Wound healing.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transdifferentiation / physiology*
  • Epithelial-Mesenchymal Transition / physiology
  • Eye Diseases / physiopathology*
  • Fibrosis / physiopathology*
  • Humans
  • Myofibroblasts / physiology*
  • Signal Transduction / physiology
  • Transforming Growth Factor beta / metabolism
  • Wound Healing / physiology*


  • Transforming Growth Factor beta