Fibrotic disorders in the eye: targets of gene therapy

Prog Retin Eye Res. 2008 Mar;27(2):177-96. doi: 10.1016/j.preteyeres.2007.12.002. Epub 2008 Feb 1.

Abstract

Fibrotic diseases, e.g., cutaneous and corneal scarring, keloids, and liver and lung fibrosis, etc., are characterized by appearance of myofibroblasts, the key player of the fibrogenic reaction, and excess accumulation of extracellular matrix with resultant tissue contraction and impaired functions. Inflammatory/fibrogenic growth factors/cytokines produced by injured tissues play a pivotal role in fibrotic tissue formation. Ocular tissues are also susceptible to fibrotic diseases. In this article, the pathogenesis of such fibrotic disorders in the eye, i.e., scarring in the cornea and conjunctiva, post-cataract surgery fibrosis of the lens capsule and proliferative vitreoretinopathy are reviewed. Focus is put on the roles of myofibroblast and signals activated by the fibrogenic cytokine, transforming growth factor beta. Modulation of signal transduction molecules, e.g., Smad and mitogen-activated protein kinases, by gene transfer and other technology is beneficial and can be an important treatment regiment to overcome (prevent or treat) these diseases.

Publication types

  • Review

MeSH terms

  • Animals
  • Conjunctiva / pathology*
  • Cornea / pathology*
  • Eye Diseases / pathology
  • Eye Diseases / therapy*
  • Fibroblasts / pathology
  • Fibrosis / therapy
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Humans
  • Lens Capsule, Crystalline / pathology*
  • Mitogen-Activated Protein Kinases / genetics
  • Retina / pathology*
  • Skin / pathology
  • Smad Proteins / genetics
  • Transforming Growth Factor beta / genetics

Substances

  • Smad Proteins
  • Transforming Growth Factor beta
  • Mitogen-Activated Protein Kinases