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Abstract #48925 Published in IGR 14-1
Current understanding of conventional outflow dysfunction in glaucoma
Stamer WD; Acott TSCurrent Opinions in Ophthalmology 2012; 23: 135-143
PURPOSE OF REVIEW: Regulation of intraocular pressure by the conventional (trabecular) outflow pathway is complicated, involving a myriad of mechanical and chemical signals. In most, intraocular pressure is maintained within a tight range over a lifetime. Unfortunately in some, dysfunction results in ocular hypertension and open-angle glaucoma. In the context of established knowledge, this review summarizes recent investigations of conventional outflow function, with the goal of identifying areas for future inquiry and therapeutic targeting. RECENT FINDINGS: Mechanical stimulation of conventional outflow cells due to intraocular pressure fluctuations impacts contractility, gene expression, pore formation, enzyme activity, and signaling. Numerous local signaling mediators in the conventional pathway such as bioactive lipids, cytokines, nitric oxide, and nucleotides participate in the regulation of outflow. Interestingly outflow through the conventional pathway is not uniform, but segmental, with passageways constantly changing due to focal protease activity of trabecular cells clearing extracellular matrix materials. The relationship between extracellular matrix expression and trabecular meshwork contractility appears to coordinately impact outflow resistance and is the target of a new class of drugs, the Rho kinase inhibitors. SUMMARY: The conventional outflow pathway is a dynamic, pressure-sensitive tissue that is vulnerable to pathology on many fronts, each representing a therapeutic opportunity.
Department of Ophthalmology, Duke University, Durham, NC, USA. Dan.stamer@duke.edu
Full articleClassification:
2.6.2.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.6 Aqueous humor dynamics > 2.6.2 Outflow)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)