Recent developments in understanding the pathophysiology of elevated intraocular pressure.

PubMed ID: 16552252

Author(s): Tan JC, Peters DM, Kaufman PL. Recent developments in understanding the pathophysiology of elevated intraocular pressure. Curr Opin Ophthalmol. 2006 Apr;17(2):168-74. Review. PMID 16552252

Journal: Current Opinion In Ophthalmology, Volume 17, Issue 2, Apr 2006

PURPOSE OF REVIEW 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.

RECENT FINDINGS 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.

SUMMARY 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.