Effects of Y-39983, a Selective Rho-Associated Protein Kinase Inhibitor, on Blood Flow in Optic Nerve Head in Rabbits and Axonal Regeneration of Retinal Ganglion Cells in Rats | Semantic Scholar (2024)

It is demonstrated that Y-39983 significantly enhanced the survival and axonal regeneration of RGCs after ONC and downregulated the expression of active-RhoA, ROCK1 and ROCK2 during its promotion of axonal Regeneration.

Fasudil treatment could significantly reduce the apoptosis of RGCs and relieved retinal nerve injury in vitro and in vivo, and showed that RhoA/Rock signaling in the retina was activated during the traumatic optic neuropathy.

The results indicate that intravitreal injection of unoprostone promotes regeneration of crushed optic nerve fibers in adult cats.

The findings show that K-115 has a potential use in neuroprotective treatment for glaucoma and other neurodegenerative diseases and that it did not suppress ROS production directly.

Preliminary human cases confirmed that ROCK inhibitor eye drops were considerably effective for treatment of corneal edema associated with cataract surgery, and ROCK inhibitor may be developed as an eye drop for treating acuteCorneal endothelial damage to prevent progression of bullous keratopathy.

Topical instillation of ripasudil increased blood flow around the ONH in the eyes of normal rats, and mean blur rate was evaluated in the total area, the vessel region, and the tissue region.

H-1152P exerted a neuroprotective effect against necrosis on the isolated bovine retina under Hypoxia together with a reduction in glial cell reactivity, however, the inhibitor could not prevent the hypoxia induced retinal dysfunction possibly due to the interference with synaptic modulation.

The Y-27632 effect on IOP in hypertensive NHP eyes is caused by increases in outflow facility and uveoscleral outflow, and an increase in aqueous humor formation attenuates but does not prevent an IOP decrease.

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Y-39983 ophthalmic solution may be a candidate drug for lowering of intraocular pressure (IOP), since it increases conventional outflow and produces relatively few side effects.

Results show that systemic or topical fasudil suppresses impairment of ONH blood flow, function, and morphology induced by L-NAME or ET-1, and a ROCK inhibitor can be useful for the treatment of impaired ONHBlood flow.

In vitro experiments suggest that the IOP-lowering effects of Y-27632 may be related to the altered cellular behavior of TM cells and relaxation of CM contraction, and suggest that ROCK inhibitors may have great potential to be developed for treatment of glaucoma and other ocular diseases.

The results demonstrate the neuroprotective effect of H-1152P-mediated ROCK-inhibition on retinal cells under stress, which may rely partly on the attenuation of glial cell reactivity.

This is the first report to show the functional role of calcium-permeable AMPA-KA receptors in cultured RGCs, which causes increases in intracellular calcium and decreases in cell survival.

The ROCK inhibitor reduced intraocular pressure in rabbits by topical instillation and relaxed the excised ciliary muscle which was previously constricted by carbachol suggesting that the inhibitor acts to increase the uveoscleral outflow.

It is shown that p160ROCK activation is necessary and sufficient for the agonist-induced neurite retraction and cell rounding, and Rho/ROCK-dependent tonic inhibition of cell process extension is exerted via activation of the actomysin-based contractility, in conjunction with a suppression of assembly of intermediate filaments and microtubules in many cell types including, but not exclusive to, neuronal cells.

The findings suggest the importance of vascular smooth muscle in maintaining stable ONH circulation against reduction of IOP in a fashion nearly independent of NO, endogenous prostaglandins, and the sympathetic nervous system.

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