Key points: An elevation in intracranial pressure (ICP) lowers conventional outflow facility (increases aqueous outflow resistance) of rat eyes. The reduction in outflow facility correlates with an increase in intraocular pressure (IOP). The effect of ICP elevation on outflow facility and IOP is blocked by TTX. The results indicate that aqueous humour dynamics is modulated by ICP-driven neural feedback from the brain. This feedback mechanism may act to stabilize translaminar pressure across the optic nerve head and may provide a new avenue for glaucoma therapy.
Abstract: While intraocular pressure (IOP) is a well-known risk factor for glaucoma, intracranial pressure (ICP) is attracting heightened interest because of its influence on optic nerve head biomechanics. Studies have shown that ICP can have marked impacts on posterior eye health by modifying the translaminar pressure gradient across the optic nerve. There is also growing evidence that IOP and ICP may be interconnected, although the mechanism of their putative interaction is unknown. We sought to test the hypothesis that ICP modulates IOP by altering aqueous humour dynamics. The anterior chamber and lateral ventricle of anaesthetized Brown-Norway rats were cannulated with fine-gauge needles connected to a programmable pump and saline reservoir, respectively. ICP was manipulated by varying reservoir height, and eye outflow facility (C) was determined from the pump flow rate required to hold IOP at different levels. C was 22 ± 4 nl/min/mmHg at resting ICP and 13 ± 3 nl/min/mmHg when ICP was raised 15 mmHg, a reduction of 41 ± 13% (n = 18). The decrease in outflow facility was independent of blood pressure, reversible, scaled with ICP elevation and correlated with increases in resting IOP. It was physiological in origin because C returned to baseline values after the rats were killed and corneal application of TTX though ICP remained elevated. These results indicate that a neural feedback mechanism driven by ICP regulates conventional outflow facility in rats. The mechanism may protect the eye from translaminar pressure swings and may offer a new target for glaucoma treatment.
Keywords: conventional outflow facility; glaucoma; intraocular pressure.
© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.