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Fiona McDonnell, W. Michael Dismuke, Darryl R Overby, W Daniel Stamer; DISTAL OUTFLOW RESISTANCE CAN BE REGULATED PHARMACOLOGICALLY. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6039.
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© ARVO (1962-2015); The Authors (2016-present)
The trabecular meshwork (TM) and Schlemm’s canal “SC” are responsible for generating the majority of outflow resistance; however three independent studies have shown that distal regions of the conventional outflow pathway account for 25-50% of total outflow resistance. Parts of these distal vessels are surrounded by α-smooth muscle actin containing cells, indicating that distal vessels may be vasoregulated. This study examined the effect of a potent vasodilator, nitric oxide (NO) and its physiological antagonist endothelin-1 (ET-1, a potent vasoconstrictor) on the regulation of outflow resistance in the distal regions of the conventional outflow pathway.
Human and porcine anterior segments, with vascular and pigmented tissues removed, were perfused in organ culture. Anterior segments were perfused under constant flow of 2.5µl/min for human and 4.5µl/min for porcine, while pressure was continually monitored. For porcine anterior segments, a stable baseline outflow facility with TM intact was first achieved before anterior segments were removed and a trabeculotomy performed. For human anterior segments a trabeculotomy was immediately performed on segments, thus an outflow facility with TM intact was not obtained.
In trabeculotomized human anterior segments (n=7), 100nM ET-1 decreased outflow facility from 0.54±0.12 to 0.33±0.08 µl/min/mmHg (Δ41.63±6.57%, P<0.01). Perfusion with DETA-NO in the presence of 1nM ET-1 immediately reversed ET-1 effects, increasing outflow facility to 0.54±0.13 µl/min/mmHg (Δ175.17±18.32%,P<0.01). Over time (6±2 hrs), we observed a rebound in facility in control eyes following a second exchange with 100nM ET-1; whereby facility returned to 0.37±0.06 µl/min/mmHg. Using a lower dose of ET-1 (1nM) in control eyes for the second exchange resulted in a facility that remained stable at 0.23±0.09 µl/min/mmHg for 72 hours (n=2). In experimental contralateral eyes, DETA-NO increased facility to 0.46±0.06 µl/min/mmHg (Δ138.25±30.26%) like the rest. The pattern of responses to ET1 and DETA-NO were similar in perfused porcine anterior segments.
Data show a dynamic range of resistance generation by distal vessels in both the human and porcine conventional outflow pathways. Interestingly, maximal contraction of vessels in the distal outflow tract generated resistance very near physiological levels for both species.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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