Fasudil, a Rho-associated protein kinase inhibitor, attenuates retinal ischemia and reperfusion injury in rats

Song, Haishan; Dian-wen, Gao

doi:10.3892/ijmm.2011.659

Cited by 15 publications

(4 citation statements)

References 24 publications

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“…Such abnormal temporary phenomenon might be triggered by several factors. On one hand, ROCK inhibitors can interfere with the apoptotic Caspase 3-ROCK signalling pathway (Song and Gao, 2011), and, consequently, increase the number of viable cells. However, a more likely explanation is that as a response to treatment with toxins within certain time-window, cells tend to increase metabolism, which manifests itself as enhanced reduction of resazurin.…”

Section: Discussionmentioning

confidence: 99%

Chemosensitivity and chemoresistance in endometriosis – differences for ectopic versus eutopic cells

Lavõgina

Samuel

Lavrits

et al. 2019

Reproductive BioMedicine Online

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RESEARCH QUESTION Endometriosis is a common gynecological disease defined by the presence of endometrium-like tissue outside uterus. This complex disease, often accompanied by severe pain and infertility, causes significant medical and socioeconomic burden; hence, novel strategies are sought for treatment of endometriosis. Here, we set out to explore cytotoxic effects of a panel of compounds to find toxins with different efficiency in eutopic versus ectopic cells, thus highlighting alterations in the corresponding molecular pathways. DESIGN Effect of 14 compounds on cellular viability was established in a cohort of paired eutopic and ectopic endometrial stromal cell samples from 11 patients. The biological targets covered by the panel included pro-survival enzymes, cytoskeleton proteins, proteasome, and cell repair machinery. RESULTS We showed that protein kinase inhibitors GSK690693, ARC-775, and sorafenib, proteasome inhibitor bortezomib, and microtubule-depolymerizing toxin MMAE, were more effective in eutopic cells. In contrast, 10 M anthracycline toxin doxorubicin caused cellular death in ectopic cells more effectively than in eutopic cells. The large-scale sequencing of mRNA isolated from doxorubicin-treated and control cells indicated different survival strategies in eutopic versus ectopic endometrium. CONCLUSIONS Overall, our results confirm the evidence of large-scale metabolic reprogramming in endometriotic cells, which underlies the observed differences in sensitivity towards toxins. The enhanced efficiency of doxorubicin interfering with redox equilibria and/or DNA repair mechanisms pinpoints key players that can be potentially used for selective targeting of ectopic lesions in endometriosis.

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Section: Discussionmentioning

confidence: 99%

Chemosensitivity and chemoresistance in endometriosis – differences for ectopic versus eutopic cells

Lavõgina

Samuel

Lavrits

et al. 2019

Reproductive BioMedicine Online

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“…A recent report has demonstrated that administration of an oral ROCK inhibitor, K115, delayed RGC death [78]. Fasudil also resulted in ischemia-related apoptosis of retinal cells by inhibiting Bax/Bcl-2, caspase-3, and iNOS in rats [79]. However, the importance of ROCK for neural degeneration in vitreoretinal diseases including DR and AMD is unknown.…”

Section: Future Directions Of Rock Inhibitors: Neuroprotectionmentioning

confidence: 99%

Rho-Kinase/ROCK as a Potential Drug Target for Vitreoretinal Diseases

Yamaguchi

Nakao

Arima

et al. 2017

Journal of Ophthalmology

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Rho-associated kinase (Rho-kinase/ROCK) was originally identified as an effector protein of the G protein Rho. Its involvement in various diseases, particularly cancer and cardiovascular disease, has been elucidated, and ROCK inhibitors have already been applied clinically for cerebral vasospasm and glaucoma. Vitreoretinal diseases including diabetic retinopathy, age-related macular degeneration, and proliferative vitreoretinoapthy are still a major cause of blindness. While anti-VEGF therapy has recently been widely used for vitreoretinal disorders due to its efficacy, attention has been drawn to new unmet needs. The importance of ROCK in pathological vitreoretinal conditions has also been elucidated and is attracting attention as a potential therapeutic target. ROCK is involved in angiogenesis and hyperpermeability and also in the pathogenesis of various pathologies such as inflammation and fibrosis. It has been expected that ROCK inhibitors will become new molecular target drugs for vitreoretinal diseases. This review summarizes the recent progress on the mechanisms of action of ROCK and their applications in disease treatment.

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“…149 R-1 , R-3 and R-4 have been further shown to protect RGCs from apoptosis. R-1 protects the retina of rats from both ischemia/reperfusion induced damage 150 and N-methyl-D-aspartate (NMDA) induced excitotoxicity. 151 In rats treated with R-4 , the number of RGCs with regenerating axons was increased.…”

Section: New Therapies In Late-stage Developmentmentioning

confidence: 99%

Discovery of Molecular Therapeutics for Glaucoma: Challenges, Successes, and Promising Directions

Donegan

Lieberman

2015

J. Med. Chem.

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Glaucoma, a heterogeneous ocular disorder affecting ~60 million people worldwide, is characterized by painless neurodegeneration of retinal ganglion cells (RGCs), resulting in irreversible vision loss. Available therapies, which decrease the common causal risk factor of elevated intraocular pressure, delay, but cannot prevent, RGC death and blindness. Notably, it is changes in the anterior segment of the eye, particularly in the drainage of aqueous humor fluid, which are believed to bring about changes in pressure. Thus, it is primarily this region whose properties are manipulated in current and emerging therapies for glaucoma. Here, we focus on the challenges associated with developing treatments, review the available experimental methods to evaluate the therapeutic potential of new drugs, describe the development and evaluation of emerging Rho-kinase inhibitors and adenosine receptor ligands that offer the potential to improve aqueous humor outflow and protect RGCs simultaneously, and present new targets and approaches on the horizon.

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Fasudil, a Rho-associated protein kinase inhibitor, attenuates retinal ischemia and reperfusion injury in rats

Cited by 15 publications

References 24 publications

Chemosensitivity and chemoresistance in endometriosis – differences for ectopic versus eutopic cells

Chemosensitivity and chemoresistance in endometriosis – differences for ectopic versus eutopic cells

Rho-Kinase/ROCK as a Potential Drug Target for Vitreoretinal Diseases

Discovery of Molecular Therapeutics for Glaucoma: Challenges, Successes, and Promising Directions

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