Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing

Okumura, Naoki; Inoue, Ryota; Okazaki, Yugo; Nakano, Shinichiro; Nakagawa, Hiroko; Kinoshita, Shigeru; Koizumi, Noriko

doi:10.1167/iovs.15-17595

Cited by 81 publications

(71 citation statements)

References 40 publications

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“…These positive changes were maintained up to the final examination, two years later in this case [35]. Last, but not least, in 2015, Okumara et al [31] reported on 3 patients who had severe corneal endothelial damage due to cataract surgery and received Y27632 eye drops. Two of them received 1 mM Y27632 eye drops administered 6 times daily in the first 4 months, and 4 times daily during the following 2 months; the third patient used the drug four times daily only for 3 months.…”

Section: Corneal Wound Healingmentioning

confidence: 58%

“…The third patient had an intact Descemet membrane but the corneal endothelial cell density was critically low (508 cells/mm 2 ). Contrary to expectations, by the third month, the cornea became clear and the visual acuity increased from the initial 20/63 to 20/25 [31]. Although these human studies have a number of limitations, for example patients without treatment were not followed and the results are very preliminary, taken together they suggest that ROCK inhibitors may be effective in reducing corneal edema, and/or improve wound healing.…”

Section: Corneal Wound Healingmentioning

confidence: 79%

“…It can detach spontaneously, or be removed during cataract surgery, or other injuries. The importance of an intact Descemet's membrane in corneal endothelial recovery has been investigated in in vitro studies [31,32]. In a rabbit organ culture model (treated with 10 µM Y27632 for 48 hours) there was no difference between the presence and absence of Descemet's membrane, and the ROCK inhibitor increased CEC proliferation to approximately the same level in both samples [31].…”

Section: Corneal Wound Healingmentioning

confidence: 99%

“…The importance of an intact Descemet's membrane in corneal endothelial recovery has been investigated in in vitro studies [31,32]. In a rabbit organ culture model (treated with 10 µM Y27632 for 48 hours) there was no difference between the presence and absence of Descemet's membrane, and the ROCK inhibitor increased CEC proliferation to approximately the same level in both samples [31]. In contrast, in human CEC culture (treated with 10 µM Y27632 for 14 days), results suggest that the presence of an intact Descemet's membrane does affect corneal endothelial wound healing [32].…”

Section: Corneal Wound Healingmentioning

confidence: 99%

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ROCK inhibitors in ocular disease

Halasz

Townes‐Anderson

2016

ADMET DMPK

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Section: Corneal Wound Healingmentioning

confidence: 58%

Section: Corneal Wound Healingmentioning

confidence: 79%

Section: Corneal Wound Healingmentioning

confidence: 99%

Section: Corneal Wound Healingmentioning

confidence: 99%

See 2 more Smart Citations

ROCK inhibitors in ocular disease

Halasz

Townes‐Anderson

2016

ADMET DMPK

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“…In a recent clinical study, Okumura et al noticed that the use of a topical ROCK inhibitor (Y-27632) could recover corneal transparency in patients with severe corneal oedema following cataract surgery. The authors concluded that ROCK inhibition promotes proliferation of the residual undamaged endothelial cells 19. In addition, previous studies have demonstrated that severe damage to CECs leads to their fibroblastic transformation and a loss of the endothelial cell pump and its barrier function.…”

Section: Introductionmentioning

confidence: 96%

ROCK inhibitors for the treatment of ocular diseases

et al. 2017

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The Rho-kinase/ROCK (Rho-associated coiled-coil-containing protein kinase) pathway is involved in the pathogenesis of multiple ocular and systemic disorders. Recently, ROCK inhibitors have been suggested as novel treatments for various ocular diseases. Several in vitro, in vivo and clinical studies have demonstrated the safety and efficacy of ROCK inhibitors in the management of ocular disorders such as corneal epithelial and endothelial damage, glaucoma, retinal and choroidal neovascularisation, diabetic macular oedema and optic nerve disorders. In this review, these studies are explored with focus on the relevant clinical investigations.

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Association of the Gutta-Induced Microenvironment With Corneal Endothelial Cell Behavior and Demise in Fuchs Endothelial Corneal Dystrophy

et al. 2018

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IMPORTANCEThe number and size of guttae increase over time in Fuchs endothelial corneal dystrophy (FECD); however, the association between these physical parameters and disease pathogenesis is unclear.OBJECTIVE To determine the role of guttae in corneal endothelial cell function. DESIGN, SETTINGS, AND PARTICIPANTSIn an in vitro model, cells from a human corneal endothelial cell line, HCENC-21T, were seeded on decellularized normal (n = 30) and FECD (n = 70) endothelial basement (Descemet) membranes (DMs). Normal human corneas were sent to our laboratory from 3 sources. The study took place at the Schepens Eye Research Institute, Massachusetts Eye and Ear, Boston, and was performed from September 2015 to July 2017. Normal DMs were obtained from 3 different tissue banks and FECD-DMs were obtained from patients undergoing endothelial keratoplasty in 2 departments. MAIN OUTCOMES AND MEASURES Endothelial cell shape, growth, and migration were assessed by live-cell imaging, and gene expression analysis as a function of guttae diameter was assessed by laser capture microscopy. RESULTS Mean (SD) age of normal-DMs donors was 65.6 (4.4) years (16 women [53%]), and mean (SD) age of FECD-DMs donors was 68.9 (10.6) years (43 women [61%]). Cells covered a greater area (mean [SD], 97.7% [8.5%]) with a greater mean (SD) number of cells (2083 [153] cells/mm 2 ) on the normal DMs compared with the FECD DMs (72.8% [11%]; P = .02 and 1541[221] cells/mm 2 221/mm 2 ; P = .01, respectively). Differences in endothelial cell growth over guttae were observed on FECD DMs depending on the guttae diameter. Guttae with a mean (SD) diameter of 10.5 (2.9) μm did not impede cell growth, whereas those with a diameter of 21.1 (4.9) μm were covered only by the cell cytoplasm. Guttae with the largest mean (SD) diameter, 31.8 (3.8) μm, were not covered by cells, which instead surrounded them in a rosette pattern. Moreover, cells adjacent to large guttae upregulated αSMA, N-cadherin, Snail1, and NOX4 genes compared with ones grown on normal DMs or small guttae. Furthermore, large guttae induced TUNEL-positive apoptosis in a rosette pattern, similar to ex vivo FECD specimens.CONCLUSIONS AND RELEVANCE These findings highlight the important role of guttae in endothelial cell growth, migration, and survival. These data suggest that cell therapy procedures in FECD might be guided by the diameter of the host guttae if subsequent clinical studies confirm these laboratory findings.

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Effect of the Rho Kinase Inhibitor Y-27632 on Corneal Endothelial Wound Healing

Abstract: ROCK inhibitor may be developed as an eye drop for treating acute corneal endothelial damage to prevent progression of bullous keratopathy. (University Hospital Medical Information Network Clinical Trial Registry no. UMIN000003625; www.umin.ac.jp/ctr).

Cited by 81 publications

References 40 publications

ROCK inhibitors in ocular disease

ROCK inhibitors in ocular disease

ROCK inhibitors for the treatment of ocular diseases

Association of the Gutta-Induced Microenvironment With Corneal Endothelial Cell Behavior and Demise in Fuchs Endothelial Corneal Dystrophy

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