Abstract
Purpose: :
To determine the effect of DNB-001, a benzopyran derivative ion channel modulator, on trabecular outflow facility of human eyes.
Methods: :
Anterior segment organ explants from three pairs of human donor eyes (ages 60F, 61M, and 80M) were placed in culture and allowed to reach stable baseline pressure. Once stable (2-4 days), one anterior segment from each pair of eyes received DNB-001 (5 µM) by anterior chamber exchange while the fellow anterior segment received vehicle (dimethylsulfoxide). Anterior segments were continuously perfused with either DNB-001 (5 µM) or vehicle at a constant flow rate of 2.5 µl/min for up to 120 hours. Outflow facility was calculated at 0, 12, 24, 72, and 120 hours. Morphology of the trabecular meshwork and Schlemm’s canal was evaluated by light microscopy.
Results: :
Trabecular outflow facility was increased in all three anterior segments that received DNB-001. In DNB-001 treated anterior segments, outflow facility was increased by 17% ± 12% (12 hours) and 18% ± 9% (24 hours) versus control. By 72 hours post-treatment with DNB-001, outflow facility had increased to 34% ± 16% versus control. In two pairs of anterior segments, treatment was extended to 120 hours. Both anterior segments treated with DNB-001 for 120 hours had a 40% increase in outflow facility when compared to control. By light microscopy, no morphological changes were observed in the trabecular meshwork or in Schlemm’s canal in either DNB-001 or vehicle treated anterior segments.
Conclusions: :
DNB-001 increased trabecular outflow facility in human eyes. Given its neuroprotective profile, DNB-001 represents a compelling and novel class of anti-glaucoma drug that may be useful in the treatment of glaucoma.
Keywords: trabecular meshwork • outflow: trabecular meshwork • intraocular pressure