Overexpression of myocilin in cultured human trabecular meshwork cells

Exp Cell Res. 2004 Jul 1;297(1):39-48. doi: 10.1016/j.yexcr.2004.02.024.

Abstract

The trabecular meshwork, a specialized eye tissue, is a major site for regulation of the aqueous humor outflow. Malfunctioning of the trabecular meshwork is believed to be responsible for development of glaucoma, a blinding disease. Myocilin is a gene linked to the most common form of glaucoma. Its expression is known to be upregulated by glucocorticoids in trabecular meshwork cells and the altered myocilin level may be the culprit for glaucomatous conditions such as corticosteroid-induced glaucoma. In this study, we examined the influence of myocilin overexpression on the adhesion, spreading, migration, phagocytosis, and apoptosis of human trabecular meshwork cells in culture. When the myocilin expression was increased by 3- to 4-fold, the transfectants showed a dramatic loss of actin stress fibers and focal adhesions. Cell adhesion to fibronectin and spreading were also compromised. Myocilin thus appeared to have a de-adhesive activity, similar to that reported extensively with matricellular proteins. The transfected cells in addition displayed an increased sensitivity to apoptosis. These results demonstrate that overexpression of myocilin renders trabecular meshwork cells in a de-adhesive and vulnerable state. This vulnerability may be the basis for pathologic consequences in subtypes of glaucoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Apoptosis / genetics
  • Aqueous Humor / physiology*
  • Cell Adhesion / genetics
  • Cell Movement / genetics
  • Cells, Cultured
  • Cytoskeletal Proteins
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Focal Adhesions / metabolism
  • Gene Expression Regulation / physiology
  • Glaucoma / genetics
  • Glaucoma / metabolism*
  • Glaucoma / physiopathology
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Middle Aged
  • Phagocytosis / genetics
  • Stress Fibers / metabolism
  • Trabecular Meshwork / cytology
  • Trabecular Meshwork / metabolism*
  • Trabecular Meshwork / physiopathology
  • Transfection
  • Up-Regulation / genetics

Substances

  • Cytoskeletal Proteins
  • Eye Proteins
  • Glycoproteins
  • trabecular meshwork-induced glucocorticoid response protein