Effects of Rho-associated protein kinase inhibitors Y-27632 and Y-39983 on isolated rabbit ciliary arteries

Watabe, Hiroshi; Abe, Sanae; Yoshitomi, Takeshi

doi:10.1007/s10384-011-0048-9

Cited by 35 publications

(20 citation statements)

References 32 publications

(45 reference statements)

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“…Clinical trials are currently in progress for the treatment of normotensive glaucoma, with methods that increase blood flow in the optic nerve, such as medications that inhibit spasm of the vessels to the eye or that raise systemic blood pressure, removing the plaque in the carotid artery if it exists, or using a catheter with a balloon inserted through the artery in plaques located in smaller or harder‐to‐reach areas, or using Rho‐associated coiled coil‐forming protein kinase (ROCK) inhibitors (Y‐27632 and Y39983) to relax rabbit ciliary arteries (Watabe et al. ).…”

Section: Discussionmentioning

confidence: 99%

Changes in peripapillary choroidal thickness in patients with multiple sclerosis

García‐Martín

Jarauta

Júlvez

et al. 2018

Acta Ophthalmologica

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Purpose: To study peripapillary choroidal thickness (PPCT) around the optic disc and establish zones using a new swept source optical coherence tomography (SS-OCT) device. To evaluate PPCT differences between patients with multiple sclerosis (MS) and age-and sex-matched healthy controls. Methods: A total of 102 healthy subjects and 51 patients with MS were consecutively recruited. Healthy subjects were divided into teaching (n = 51, used to establish choroidal zones) and validating (n = 51, used to compare measurements with MS patients) populations. An optic disc 6.0 3 6.0-mm three-dimensional scan was obtained using SS-OCT Triton. A 26 3 26 cube-grid centred on the optic disc was generated automatically to measure PPCT. Four choroidal zones were established and used to compare PPCT between healthy controls and patients with MS. Results: Peripapillary choroidal thickness (PPCT) was significantly thinner in patients in all concentric zones (p ≤ 0.0001): 134.02 AE 16.59 lm in MS group versus 171.56 AE 12.43 lm in the control group in zone 2; 182.23 AE 20.52 versus 219.03 AE 17.99 lm, respectively, in zone 3; and 223.52 AE 10.70 versus 259.99 AE 10.29 lm, respectively, in zone 4. The choroidal thinning in the MS group tended to decrease as we distanced from the optic nerve head. Peripapillary choroidal thickness (PPCT) had a similar pattern in controls and MS; it was thicker in the superior region, followed by temporal, nasal and inferior regions. Conclusion: Patients with MS showed peripapillary choroidal thinning when compared with healthy subjects in all zones around the optic disc. Peripapillary choroidal tissue shows a concentric pattern, increasing in thickness when increasing the distance from the optic nerve. The new SS-OCT could be useful for evaluating choroidal thinning in clinical practice.

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Section: Discussionmentioning

confidence: 99%

Changes in peripapillary choroidal thickness in patients with multiple sclerosis

García‐Martín

Jarauta

Júlvez

et al. 2018

Acta Ophthalmologica

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“…16 Although conjunctival hyperemia was seen in more than half of the patients treated with AR-13324, its vasodilatory activity was transient, as evidenced by the lower incidence of conjunctival hyperemia as scored by biomicroscopic examination in the morning relative to the incidence of hyperemia in the adverse event reports, which included patient-reported eye redness after dosing in the evening. The biomicroscopy examinations also revealed that the incidence of hyperemia decreased throughout the study for AR-13324.…”

Section: Discussionmentioning

confidence: 99%

Double-masked, Randomized, Dose–Response Study of AR-13324 versus Latanoprost in Patients with Elevated Intraocular Pressure

Bacharach¹,

DuBiner²,

Levy³

et al. 2015

Ophthalmology

130

128

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“…27 The conjunctival hyperemia observed in netarsudil/latanoprost FDC-treated and netarsudil-treated patients is possibly caused by the vasodilatory effects of ROCK inhibition. [28][29][30][31] Conjunctival hemorrhages were observed intermittently via biomicroscopy in patients treated with netarsudil/ latanoprost FDC or single-agent netarsudil and generally resolved with continued dosing. Cornea verticillata, which is a collection of lipid microdeposits localized to the corneal epithelium, was reported in < _5% of netarsudil/latanoprost FDC-treated and netarsudiltreated patients.…”

Section: In the Primary Efficacy Analysis Of This Study Ofmentioning

confidence: 99%

Netarsudil/Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure: Three-Month Data from a Randomized Phase 3 Trial

Robin

Serle

Lewis

et al. 2019

American Journal of Ophthalmology

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PURPOSE: To compare the ocular hypotensive efficacy and safety of a fixed-dose combination (FDC) of the Rho kinase inhibitor netarsudil and latanoprost vs monotherapy with netarsudil or latanoprost. DESIGN: Three-month primary endpoint analysis of a randomized, double-masked, phase 3 clinical trial. METHODS: Adults with open-angle glaucoma or ocular hypertension (unmedicated intraocular pressure [IOP] >20 and <36 mm Hg at 8:00 AM) were randomized to receive once-daily netarsudil/latanoprost FDC, netarsudil 0.02%, or latanoprost 0.005% for up to 12 months. The primary efficacy endpoint was mean IOP at 8:00 AM, 10:00 AM, and 4:00 PM at week 2, week 6, and month 3. RESULTS: Mean treated IOP ranged from 14.8-16.2 mm Hg for netarsudil/latanoprost FDC, 17.2-19.0 mm Hg for netarsudil, and 16.7-17.8 mm Hg for latanoprost. Netarsudil/latanoprost FDC met the criteria for superiority to each active component at all 9 time points (all P < .0001), lowering IOP by an additional 1.8-3.0 mm Hg vs netarsudil and an additional 1.3-2.5 mm Hg vs latanoprost. At month 3, the proportion of patients achieving mean diurnal IOP £15 mm Hg was 43.5% for netarsudil/ latanoprost FDC, 22.7% for netarsudil, and 24.7% for latanoprost. No treatment-related serious adverse events were reported; treatment-related systemic adverse events were minimal. The most frequent ocular adverse event was conjunctival hyperemia (netarsudil/latanoprost FDC, 53.4%; netarsudil, 41.0%; latanoprost, 14.0%), which led to treatment discontinuation in 7.1% (netarsudil/lata-noprost FDC), 4.9% (netarsudil), and 0% (latanoprost) of patients. CONCLUSIONS: Once-daily netarsudil/latanoprost FDC demonstrated IOP reductions that were statistically and clinically superior to netarsudil and latanoprost across all 9 time points through month 3, with acceptable ocular safety.

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Effects of Rho-associated protein kinase inhibitors Y-27632 and Y-39983 on isolated rabbit ciliary arteries

Abstract: We concluded that Y-27632 and Y-39983 relaxed isolated rabbit ciliary artery segments in vitro. The mechanism of relaxation was not dependent on endothelial-derived factors such as nitric oxide (NO) or prostacyclin, nor was it dependent on changes in intracellular Ca(2+) concentration.

Cited by 35 publications

References 32 publications

Changes in peripapillary choroidal thickness in patients with multiple sclerosis

Changes in peripapillary choroidal thickness in patients with multiple sclerosis

Double-masked, Randomized, Dose–Response Study of AR-13324 versus Latanoprost in Patients with Elevated Intraocular Pressure

Netarsudil/Latanoprost Fixed-Dose Combination for Elevated Intraocular Pressure: Three-Month Data from a Randomized Phase 3 Trial

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