TY  - JOUR
A1  - Chen, Si
A1  - Waxman, Susannah
A1  - Wang, Chao
A1  - Atta, Sarah
A1  - Loewen, Ralitsa
A1  - Loewen, Nils A.
T1  - Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract
JF  - Graefe's Archive for Clinical and Experimental Ophthalmology
N2  - Purpose
To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). Wehypothesized 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 10μM netarsudil (N= 8 eyes per concentration). For each concentration,IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters wereassessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series).

Results
Netarsudil at 1μM 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 0.1μMnetarsudilelevated 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 10μM elevated IOP both in eyeswith 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 tractvessels constricted by 27%.

Conclusion
In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameterchanges of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal
KW  - Rho-kinase inhibitor
KW  - Netarsudil
KW  - Distal outflow trac
KW  - Anterior chamber perfusion model
KW  - Porcine eye
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231893
SN  - 0721-832X
VL  - 258
ER  -