Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract.
Animals
Aqueous Humor
/ physiology
Benzoates
/ administration & dosage
Dose-Response Relationship, Drug
Intraocular Pressure
/ drug effects
Ocular Physiological Phenomena
Organ Culture Techniques
Protein Kinase Inhibitors
/ administration & dosage
Sclera
/ blood supply
Swine
Tomography, Optical Coherence
Tonometry, Ocular
Trabecular Meshwork
/ diagnostic imaging
Trabeculectomy
Veins
/ diagnostic imaging
beta-Alanine
/ administration & dosage
rho-Associated Kinases
/ antagonists & inhibitors
Anterior chamber perfusion model
Distal outflow tract
Netarsudil
Porcine eyes
Rho-kinase inhibitor
Journal
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
ISSN: 1435-702X
Titre abrégé: Graefes Arch Clin Exp Ophthalmol
Pays: Germany
ID NLM: 8205248
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
received:
28
11
2019
accepted:
07
04
2020
revised:
24
03
2020
pubmed:
7
5
2020
medline:
7
4
2021
entrez:
7
5
2020
Statut:
ppublish
Résumé
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. 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). 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%. 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.
Identifiants
pubmed: 32372330
doi: 10.1007/s00417-020-04691-y
pii: 10.1007/s00417-020-04691-y
pmc: PMC7237522
doi:
Substances chimiques
Benzoates
0
Protein Kinase Inhibitors
0
beta-Alanine
11P2JDE17B
rho-Associated Kinases
EC 2.7.11.1
netarsudil
W6I5QDT7QI
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1211-1216Subventions
Organisme : NIH HHS
ID : P30-EY08098
Pays : United States
Organisme : Xiangya Hospital of Central South University
ID : fellowship award
Organisme : Research to Prevent Blindness
ID : Departmental Grant
Organisme : Eye and Ear Foundation of Pittsburgh
ID : Initiative to Cure Glaucoma
Organisme : Julius-Maximilians-Universität Würzburg
ID : Unrestricted Departmental
Organisme : NEI NIH HHS
ID : K08EY022737
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY008098
Pays : United States
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