The trabecular meshwork is a tissue located in the anterior chamber angle of the eye, and it is a crucial determinant of intraocular pressure values because of its resistance to the evacuation of aqueous humor from the eye. Here we bring together classical and recent discoveries on the function of the trabecular meshwork, keys to understanding eye pathophysiology.
Cell swelling activates a regulatory volume decrease mechanism that implies activation of K(+) and Cl(-) currents and participation of P2Y(2) receptors. Because previous studies have shown that intracellular volume of TM cells is an important determinant of outflow facility, it seems feasible that cell volume regulation would be part of the homeostatic mechanisms of the TM, to regulate the outflow pathway.
Sensory nerve fibers innervating the ocular anterior surface detect external stimuli producing innocuous and painful sensations. Protons are among the first mediators released by damaged cells during inflammation, tissue injury, or other chronic ophthalmic conditions. We studied whether acid-sensing ion channels (ASICs) are expressed in corneal sensory neurons and their roles in the response to moderate acidifications of the ocular surface and in pathologies producing ocular surface inflammation. Moderate acidic pH (6.6) activated ASIC-like currents in corneal sensory neurons, which were blocked by ASIC1- or ASIC3-specific toxins. Acidic pH depolarizes corneal sensory neurons to fire action potentials, an effect blocked by the ASIC3 inhibitor APETx2. 2-Guanidino-4-methylquinazoline, an ASIC3 agonist, activated a population of corneal polymodal sensory nerve fibers and significantly increased the blinking and tearing rate. The nocifensive behaviors produced by application of either a moderate acidic stimulus or ophthalmic drugs formulated in acidic solution were abolished by ASIC blockers. In a model of allergic keratoconjunctivitis, nocifensive behavior was greatly reduced by ASIC3 blockade, presumably by reducing nociceptor sensitization during the inflammatory process. Our results show that, in addition to the established role of TRPV1, ASICs play a significant role in the detection of acidic insults at the ocular surface. The identification of ASICs in corneal neurons and their alterations during different diseases is critical for the understanding of sensory ocular pathophysiology. They are likely to mediate some of the discomfort sensations accompanying several ophthalmic formulations and may represent novel targets for the development of new therapeutics for ocular pathologies.
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