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Editors Selection IGR 12-1

Medical Treatment: Regulating Outflow Resistance post-Schlemm

Comment by Fotis Topouzis on:

76886 Pharmacological regulation of outflow resistance distal to Schlemm's canal, McDonnell F; Dismuke WM; Overby DR et al., American Journal of Physiology and Cell Physiology, 2018; 315: C44-C51

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McDonnell and colleagues examined the effect of a potent vasodilator, nitric oxide (NO), and its physiological antagonist, endothelin-1 (ET-1), on the regulation of outflow resistance in the distal regions of the conventional outflow pathway.

Human and porcine anterior segments were perfused in organ culture under constant flow conditions, while intrachamber pressure was continually monitored.

In human anterior segments, 100 nM ET-1 significantly decreased distal outflow facility from 0.49 ± 0.26 to 0.31 ± 0.18(mean ± SD) µl-min-1 mmHg, P < 0.01. Perfusion with 100 µ &MICRO; diethylenetriamine- NO in the presence of 1n M ET-1 immediately reversed ET-1 effects, significantly increasing distal outflow facility to 0.54 ± 0.35 µ1 min ^-1 mmHg, P = 0.01. Similar results were obtained in porcine anterior segment experiments. The data show a dynamic range of resistance generation by distal vessels in both the human and porcine conventional outflow pathways.

The majority of current daily pharmacological treatments do not target the conventional outflow, but rather target the production of aqueous humor by the ciliary body or drainage through the unconventional outflow pathway. Current glaucoma treatments that target the conventional outflow pathway are often destructive, involve applying laser energy to the Trabecular Meshwork (TM) tissues or surgical removal/bypass of the TM and inner wall of Schlemm's Canal.

This study provides data on the outflow resistance of the conventional pathway and specifically of the distal vasculature, including collector channels, aqueous veins, and intrascleral venous plexus.

Increasing knowledge in distal conventional outflow resistance would be very valuable. Potential treatment development targeting distal conventional outflow would provide an innovative approach in glaucoma management.

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