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Fiona McDonnell, Heather Schmitt, Alex Huang, Joseph Sherwood, Darryl Overby, Daniel Stamer; Visualization of Vasoregulator Effects on Distal Outflow Vessels in Human Anterior Segments. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2718.
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The trabecular meshwork (TM) and the inner wall of Schlemm’s canal (SC) are widely accepted as the primary source(s) of outflow resistance. It has been demonstrated that vessels distal to SC play a role in outflow resistance generation and are responsible for up to 50% of total resistance, and that their vasomotion affects outflow facility. Thus, IOP-lowering therapies may be more effective if targeted to both the proximal and distal regions of the conventional outflow pathway. Here we visualize the effects of the vasoregulators, endothelin-1 (ET-1) and diethylenetriamine/nitric oxide (DETA-NO) on distal vessel lumen diameter in real time.
Methods: We used the human anterior segment perfusion model under constant flow conditions (2.5µl/min) while continuously monitoring intrachamber pressure using iOnlyHuman software. Cadaveric eyes (n=2) were perfused, and a stable baseline was achieved before treatment. After 24 hours, anterior segments were removed, trabeculotomised and reseated onto the chambers, to isolate the distal region of the conventional outflow pathway. Fluid in the anterior segments was exchanged with the vasoconstrictor ET-1, perfused for 1 hour, and then exchanged with the vasodilator DETA-NO. We imaged the vessels by spectral domain optical coherence tomography (SD-OCT) using the Spectralis FLEX. Masked analysis of intrascleral vessel lumen and collector channel cross-sectional areas was conducted in ImageJ. Data is presented as Mean±Standard Deviation.
In trabeculotomised anterior segments, we found that ET-1 (100nM) decreased collector channel lumen dimensions by 50±17% (P<0.01) and intrascleral vessel lumen cross-sectional areas by 27±28%. In contrast, when the nitric oxide donor DETA-NO (100μM) was introduced subseqeuntly, collector channel dimensions increased by 77±20% (P<0.05) compared to ET-1. Intrascleral vessel lumen cross-sectional areas were increased by 22±14% after exchange with DETA-NO (100μM) compared to ET-1.
Our data shows that the endogenous vasoregulators ET-1 and DETA-NO affect distal vessel lumen cross-sectional areas and collector channels indicating a role for these in regulating outflow resistance.
This is a 2020 ARVO Annual Meeting abstract.
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