No cell is an island: trabecular meshwork ion channels as sensors of the ambient milieu




Regulation of intraocular pressure (IOP) in the mammalian eye is itself pressure-dependent, with aqueous fluid drainage dynamics functioning as the linchpin of IOP homeostasis. Pressure autoregulation in the healthy eye requires efficient mechanotransduction by trabecular meshwork (TM) cells but is compromised in glaucoma, a devastating blinding disease. This chapter reviews the potential functions of polymodal force-transducing (mechanosensitive) ion channels expressed in TM cells as integrators of various facets of the biomechanical milieu within the anterior eye. The flow of aqueous humor imposes shear, tensile, osmotic, and compressive stress on ocular cells, providing steady-state mechanical information that must be integrated with cells’ metabolism, filtering, phagocytic, and contractile activities to maintain function. Recent studies indicate that such integration requires pressure-dependent activation of the non-selective cation channel TRPV4 and two-pore TREK-1 potassium channel, which control cells’ voltage, calcium homeostasis, cytoskeletal dynamics, and architecture (“tensegrity”). The relative balance between TRPV4 vs TREK-1 channels may be modulated by the lipid icroenvironment (cholesterol, polyunsaturated fatty acids, lipid rafts, fluidity), and protons. TRPV4- and TREK-1-dependent mechanotransduction thus integrates the functional status of TM cells with local biomechanical and biochemical milieus, repre-senting a homeostatic system for intraocular pressure regulation.

Glaucoma Research 2020-2022, pp. 35-44 #4
Edited by: Paul A. Knepper and John R. Samples
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