Ripasudil Hydrochloride Hydrate

Effect of topical administration of a Rho kinase inhibitor, ripasudil, on epithelial wound healing in a mouse cornea was investigated. Effects of treatment of cultured human corneal epithelial cell (HCEC) line and organ-cultured corneal epithelium with ripasudil on expression of p-ERK was also examined.

Epithelial defects with a diameter of 2.0 mm were prepared in the central corneas of C57BL/6 mice with or without 1-week travoprost pre-treatment, to which ripasudil or PBS as a control was instilled every 6 h immediately after preparation. The mice eyes were cultured with or without travoprost for 24-hrs. The expression levels of p-ERK in epithelium of mice eyes were compared by immunostaining after further 24-hrs culture with or without ripasudil for 24-hrs. HCEC were cultured with or without ripasudil and processed for examination for proliferation activity and protein expression of p-ERK by either immunostaining or Western blotting. The cells were also treated with or without travoprost for 24-hrs, and were further cultured with or without ripasudil. Expression levels of p-ERK were examined by Western blotting.

Ripasudil treatment suppressed post-debridement epithelial healing in association with reduced proliferation activity in peripheral (limbal) epithelium in cornea with or without pre-treatment with travoprost. Ripasudil treatment accelerated p-ERK expression. Ripasudil supplementation upregulated proliferation with increased p-ERK in HCEC.

Ripasudil treatment promotes wound healing of the mouse corneal epithelium by enhancing cell proliferation on peripheral (limbal) epithelium.

Topical therapies targeting Rho-associated protein kinase (ROCK) signalling, including netarsudil (Rhopressa®) and ripasudil (Glanatec®), have become widely adopted as part of standard clinical practice to lower intraocular pressure (IOP) in patients with ocular hypertension or glaucoma. Given the pleiotropic roles of ROCK signalling, ROCK inhibition has the potential to cause unintended ocular side effects beyond IOP lowering in other substructures of the eye, both beneficial and deleterious. Additional experience and observation of patients treated with this class of medications have uncovered both new side effects not reported in the initial clinical trials, as well as potential benefits that have inspired off-label uses and that have been the topic of numerous clinical studies, case series, case reports, and translational studies. Here, we performed a comprehensive systematic review and identified 170 studies describing ocular effects of ROCK inhibition. In addition to describing well-established ocular effects associated with inhibition of ROCK signalling, such as conjunctival hyperaemia, corneal verticillata, and reticular corneal epithelial oedema, we also highlight other effects, such as corneal haemorrhages, changes in corneal contour, anterior subcapsular opacities, contact dermatitis, punctal stenosis, and eyelid wound dehiscence, which have been described in case series and case reports. Finally, we evaluated studies describing potential novel applications of ROCK inhibition for treating disorders affecting the cornea, the retina, and the optic nerve, finding strong evidence in support of a beneficial effect of ROCK inhibitors on corneal oedema due to corneal endothelial cell dysfunction. The other potential applications require further research.