Trabecular meshwork and outflow

Core Concepts • iOP elevation results from increased outflow resistance in the outflow pathways: the trabecular meshwork (TM) and the uveoscleral pathway. • steady-state iOP is found in normal eyes where iOP builds up in response to inflow of aqueous humour to the level sufficient to drive fluid across the resistance of the outflow pathways. • in most glaucomatous eyes, the resistance of the outflow pathways is unusually high, causing an elevated iOP. • With increasing age the uveoscleral outflow declines and the TM pathway increasingly dominates. • As the TM seems to be a responsive self-aware, self-regulating tissue, it is a potential target for therapeutics aimed at enhancing outflow such as rho-kinase modulators, protein kinase inhibitor H7, cytochalasins and latrunculins. • The TM is affected by TGFβ2 and consequent downstream mediators that change the extracellular matrix. • Adenosine A1 and A2a agonists are being developed as iOP lowering therapies. • understanding how the outflow system functions is critical to determinine how to effectively manipulate elements of the system for therapeutic effect. The glaucomas are a leading cause of blindness globally, and their prevalence is increasing as the population ages. Primary open-angle glaucoma (POAG) is the most common form of the disease, although in some regions of Asia angle closure glaucoma (ACG) is more prevalent. POAG is predominantly composed of high-tension glaucoma (HTG), where intraocular pressure (IOP) is “raised” (IOP >21 mmHg). Normal-tension glaucoma (NTG), which is another important subgroup of POAG, is an optic neuropathy similar to HTG, in which IOP levels are within the statistically normal range (IOP ≤21 mmHg). Lowering IOP reduces the risk of disease 3. Feltgen N, Leifert D, Funk J. Correlation between central corneal thickness, applanation tonometry, and direct intracameral iOP readings. British Journal of Ophthalmology 2001;85:85–7.