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Graefe's Archive for Clinical and Experimental Ophthalmology

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Open Access 01-06-2020 | Glaucoma | Basic Science

Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract

Authors: Si Chen, Susannah Waxman, Chao Wang, Sarah Atta, Ralitsa Loewen, Nils A. Loewen

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 6/2020

Abstract

Purpose

To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). We hypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT) that removes the TM.

Methods

Sixty-four porcine anterior segment cultures were randomly assigned to groups with (n = 32) and without circumferential AIT (n = 32). Cultures were exposed to 0.1, 1, and 10 μM netarsudil (N = 8 eyes per concentration). For each concentration, IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters were assessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series).

Results

Netarsudil at 1 μM reduced IOP both in eyes with TM (− 0.60 ± 0.24 mmHg, p = 0.01) and in eyes without TM (− 1.79 ± 0.42 mmHg, p < 0.01). At this concentration, vessels of the distal outflow tract dilated by 72%. However, at 0.1 μM netarsudil elevated IOP in eyes with TM (1.59 ± 0.36 mmHg, p < 0.001) as well as in eyes without TM (0.23 ± 0.32 mmHg, p < 0.001). Vessels of the distal outflow tract constricted by 31%. Similarly, netarsudil at a concentration of 10 μM elevated IOP both in eyes with TM (1.91 ± 0.193, p < 0.001) and in eyes without TM (3.65 ± 0.86 mmHg, p < 0.001). At this concentration, outflow tract vessels constricted by 27%.

Conclusion

In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameter changes of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal.

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Title: Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract
Authors: Si Chen
Susannah Waxman
Chao Wang
Sarah Atta
Ralitsa Loewen
Nils A. Loewen
Publication date: 01-06-2020
Publisher: Springer Berlin Heidelberg
Keyword: Glaucoma
Published in: Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 6/2020
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI: https://doi.org/10.1007/s00417-020-04691-y

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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