Recent developments in understanding the pathophysiology of elevated intraocular pressure.
OBJECTIVE
The state of the actin cytoskeleton and adhesions of trabecular meshwork cells are important determinants of fluid outflow through the trabecular meshwork. Dysregulation of these subcellular structures or cell loss itself, is expected to adversely affect aqueous humour dynamics and intraocular pressure. This article reviews recent research into the regulation of the cytoskeleton and cell adhesions within the trabecular meshwork.


RESULTS
Key cytoskeleton regulatory pathways in trabecular meshwork cells and their extracellular matrix significantly influence outflow facility. Integrins and matrix proteins play an important part in cell-matrix communication and mediate trabecular meshwork cytoskeletal changes. Increased cross-linking of the actin cytoskeleton may render the trabecular meshwork stiffer and more resistant to aqueous outflow. In-vitro studies show that transforming growth factor-beta induces actin stress fibres in trabecular meshwork cells, indicating that the cells become more contractile. Myocilin and the heparin II domain of fibronectin also influence the actin cytoskeleton. Mutated myocilin appears to affect trabecular meshwork cells differently from wild-type myocilin and can reduce cell survival. Reduced cell survival is also associated with primary open angle glaucoma, ageing, cellular senescence and oxidative insults.


CONCLUSIONS
These findings represent advances in understanding physiological and pathogenic mechanisms within the trabecular meshwork that are relevant to intraocular pressure regulation in health and glaucoma. They pave the way for future research on the pathogenesis of glaucoma and new targets for glaucoma therapy.
Tan
James C H
JC
Department of Ophthalmology & Visual Sciences, University of Wisconsin-Madison, Wisconsin, USA.
Peters
Donna M
DM
Kaufman
Paul L
PL
D000199:Actins / Q000502:physiology; D002448:Cell Adhesion / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology; D003599:Cytoskeleton / Q000502:physiology*; D005136:Eye Proteins / Q000502:physiology; D005902:Glaucoma, Open-Angle / Q000503:physiopathology*; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology*; D014129:Trabecular Meshwork / Q000503:physiopathology*; D000099179:Myocilin
D000199:Actins; D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin