The Experts below are selected from a list of 1611 Experts worldwide ranked by ideXlab platform

Noriko Koizumi - One of the best experts on this subject based on the ideXlab platform.

  • effect of the rho associated kinase inhibitor eye drop ripasudil on corneal endothelial wound healing
    Investigative Ophthalmology & Visual Science, 2016
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Shigeru Kinoshita, Kazuya Kakutani, Noriko Koizumi
    Abstract:

    PURPOSE Ripasudil (Glanatec), a selective rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved as a glaucoma and ocular hypertension treatment in Japan in 2014. The purpose of this study was to investigate the feasibility of using ripasudil eye drops to treat corneal endothelial injuries. METHODS Cultured human corneal endothelial cells (HCECs) were treated with ripasudil, and 5-bromo-2'-deoxyuridine (BrdU) incorporation was evaluated by ELISA. A rabbit corneal endothelial damage model was also created by mechanically scraping the corneal endothelium, followed by topical ripasudil eye drop application for 2 weeks. The anterior segment was evaluated by Slit-Lamp Microscopy, and central corneal thickness was measured by ultrasound pachymetry. Corneal specimens were evaluated by phalloidin staining and immunohistochemical analysis using antibodies against Ki67, N-cadherin, and Na+/K+-ATPase. RESULTS Many more BrdU-positive cells were observed among the HCECs treated with ripasudil (0.3-30 μM) than among the control HCECs. Ripasudil-treated eyes in a rabbit model showed 91.5 ± 2.0% Ki67-positive cells after 48 hours, whereas control eyes showed 52.6 ± 1.3%. Five of six corneas became transparent in ripasudil-treated eyes, whereas zero of six corneas became transparent in the control eyes. Regenerated cell densities were higher in the eyes treated with ripasudil than in eyes treated with vehicle. Eyes treated with ripasudil expressed N-cadherin and Na+/K+-ATPase in almost all CECs, whereas this expression was decreased in control eyes. CONCLUSIONS Ripasudil promoted corneal endothelial wound healing, supporting its development as eye drops for treating acute corneal endothelial damage due to eye surgeries, especially cataract surgery.

  • Effect of the Rhoassociated kinase inhibitor eye drop (ripasudil) on corneal endothelial wound healing. Invest Ophthalmol Vis Sci.
    2016
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Nigel J Fullwood, Shigeru Kinoshita, Noriko Koizumi
    Abstract:

    PURPOSE. Ripasudil (Glanatec), a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved in Japan in September 2014 for the treatment of glaucoma and ocular hypertension. The purpose of this study was to investigate the effect of ripasudil eye drops on corneal endothelial morphology, as ROCK signaling is known to modulate the actin cytoskeleton. METHODS. Morphological changes in the corneal endothelium were evaluated in human subjects by specular and Slit-Lamp Microscopy, following topical administration of ripasudil. We also used a rabbit model to evaluate the effect of ripasudil on clinical parameters of the corneal endothelium. Twenty-four hours after ripasudil application, corneal specimens were evaluated by phalloidin staining, immunohistochemical analysis, and electron Microscopy. RESULTS. Specular Microscopy revealed morphological changes in human eyes, and Slit-Lamp Microscopy showed guttae-like findings. The rabbit model showed morphological changes similar to those seen in human eyes after ripasudil administration. Electron Microscopy demonstrated that these alterations are due to the formation of protrusions along the cell-cell borders, but this formation is transient. Expression of corneal endothelial function-related markers was not disrupted; corneal thickness and corneal volume were not changed; and no cell death was observed following ripasudil administration. CONCLUSIONS. Ripasudil induces transient guttae-like findings in humans, most likely due to protrusion formation along intracellular borders caused by the reduction in actomyosin contractility of the corneal endothelial cells. No severe adverse effects were observed. Physicians should be aware that ROCK inhibitors can cause these guttae-like findings, to avoid misdiagnosing patients as having Fuchs endothelial corneal dystrophy. (www.umin.ac.jp/ctr number, UMIN000018340.

  • Rho-associated kinase inhibitor eye drop (ripasudil) transiently alters the morphology of corneal endothelial cells.
    2016
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Shigeru Kinoshita, Noriko Koizumi, Kazuya Kakutani
    Abstract:

    PURPOSE. Ripasudil (Glanatec), a selective rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved as a glaucoma and ocular hypertension treatment in Japan in 2014. The purpose of this study was to investigate the feasibility of using ripasudil eye drops to treat corneal endothelial injuries. METHODS. Cultured human corneal endothelial cells (HCECs) were treated with ripasudil, and 5-bromo-2 0 -deoxyuridine (BrdU) incorporation was evaluated by ELISA. A rabbit corneal endothelial damage model was also created by mechanically scraping the corneal endothelium, followed by topical ripasudil eye drop application for 2 weeks. The anterior segment was evaluated by Slit-Lamp Microscopy, and central corneal thickness was measured by ultrasound pachymetry. Corneal specimens were evaluated by phalloidin staining and immunohistochemical analysis using antibodies against Ki67, N-cadherin, and Na RESULTS. Many more BrdU-positive cells were observed among the HCECs treated with ripasudil (0.3-30 lM) than among the control HCECs. Ripasudil-treated eyes in a rabbit model showed 91.5 6 2.0% Ki67-positive cells after 48 hours, whereas control eyes showed 52.6 6 1.3%. Five of six corneas became transparent in ripasudil-treated eyes, whereas zero of six corneas became transparent in the control eyes. Regenerated cell densities were higher in the eyes treated with ripasudil than in eyes treated with vehicle. Eyes treated with ripasudil expressed N-cadherin and Na þ /K þ -ATPase in almost all CECs, whereas this expression was decreased in control eyes. CONCLUSIONS. Ripasudil promoted corneal endothelial wound healing, supporting its development as eye drops for treating acute corneal endothelial damage due to eye surgeries, especially cataract surgery

  • rho associated kinase inhibitor eye drop ripasudil transiently alters the morphology of corneal endothelial cells
    Investigative Ophthalmology & Visual Science, 2015
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Nigel J Fullwood, Shigeru Kinoshita, Noriko Koizumi
    Abstract:

    PURPOSE: Ripasudil (Glanatec), a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved in Japan in September 2014 for the treatment of glaucoma and ocular hypertension. The purpose of this study was to investigate the effect of ripasudil eye drops on corneal endothelial morphology, as ROCK signaling is known to modulate the actin cytoskeleton. METHODS: Morphological changes in the corneal endothelium were evaluated in human subjects by specular and Slit-Lamp Microscopy, following topical administration of ripasudil. We also used a rabbit model to evaluate the effect of ripasudil on clinical parameters of the corneal endothelium. Twenty-four hours after ripasudil application, corneal specimens were evaluated by phalloidin staining, immunohistochemical analysis, and electron Microscopy. RESULTS: Specular Microscopy revealed morphological changes in human eyes, and Slit-Lamp Microscopy showed guttae-like findings. The rabbit model showed morphological changes similar to those seen in human eyes after ripasudil administration. Electron Microscopy demonstrated that these alterations are due to the formation of protrusions along the cell-cell borders, but this formation is transient. Expression of corneal endothelial function-related markers was not disrupted; corneal thickness and corneal volume were not changed; and no cell death was observed following ripasudil administration. CONCLUSIONS: Ripasudil induces transient guttae-like findings in humans, most likely due to protrusion formation along intracellular borders caused by the reduction in actomyosin contractility of the corneal endothelial cells. No severe adverse effects were observed. Physicians should be aware that ROCK inhibitors can cause these guttae-like findings, to avoid misdiagnosing patients as having Fuchs endothelial corneal dystrophy. (www.umin.ac.jp/ctr number, UMIN000018340.).

  • the rock inhibitor eye drop accelerates corneal endothelium wound healing
    Investigative Ophthalmology & Visual Science, 2013
    Co-Authors: Naoki Okumura, Noriko Koizumi, Eunduck P Kay, Morio Ueno, Yuji Sakamoto, Shinichiro Nakamura, Junji Hamuro, Shigeru Kinoshita
    Abstract:

    Purpose To evaluate the effect of Rho kinase (ROCK)-inhibitor eye drops on a corneal endothelial dysfunction primate model and human clinical case series of corneal endothelial dysfunction. Methods As a corneal-endothelial partially injured model, the corneal endothelium of seven cynomolgus monkeys was damaged by transcorneal freezing; 10 mm of rock inhibitor Y-27632 was then applied topically 6 times daily. The phenotype of the reconstructed corneal endothelium was evaluated by immunohistochemical analysis and noncontact specular Microscopy. For clinical study, the effect of Y-27632 eye drops after transcorneal freezing was evaluated in eight corneal endothelial dysfunction patients: four central corneal edema patients and four diffuse corneal edema patients. Results Slit-Lamp Microscopy revealed that both Y-27632-treated and -nontreated corneas became hazy after transcorneal freezing, and then recovered their transparency within 4 weeks. ROCK inhibitor Y-27632 promoted recovery of corneal endothelial cell density and wound healing in terms of both morphology and function. The percentage of ZO-1 and Na(+)/K(+)-ATPase positive cells in the regenerated area in the Y-27632 group was significantly higher than in the controls. Noncontact specular Microscopy revealed that corneal endothelial cell density was significantly higher in the Y-27632 group compared with the controls at 4 weeks; cell density reached approximately 3000 cells/mm(2), as opposed to 1500 cells/mm(2) in the control group. In addition to the animal study findings, the clinical study findings showed that Y-27632 eye drops effectively improved corneal edema of corneal endothelial dysfunction patients with central edema. Conclusions These findings show that rock inhibitor Y-27632 eye drops promote corneal endothelial wound healing in a primate animal model and suggest the possibility of Y-27632 as a novel therapeutic modality for certain forms of corneal endothelial dysfunction. (http://www.umin.ac.jp/ctr/ number, UMIN000003625.).

Shigeru Kinoshita - One of the best experts on this subject based on the ideXlab platform.

  • effect of the rho associated kinase inhibitor eye drop ripasudil on corneal endothelial wound healing
    Investigative Ophthalmology & Visual Science, 2016
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Shigeru Kinoshita, Kazuya Kakutani, Noriko Koizumi
    Abstract:

    PURPOSE Ripasudil (Glanatec), a selective rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved as a glaucoma and ocular hypertension treatment in Japan in 2014. The purpose of this study was to investigate the feasibility of using ripasudil eye drops to treat corneal endothelial injuries. METHODS Cultured human corneal endothelial cells (HCECs) were treated with ripasudil, and 5-bromo-2'-deoxyuridine (BrdU) incorporation was evaluated by ELISA. A rabbit corneal endothelial damage model was also created by mechanically scraping the corneal endothelium, followed by topical ripasudil eye drop application for 2 weeks. The anterior segment was evaluated by Slit-Lamp Microscopy, and central corneal thickness was measured by ultrasound pachymetry. Corneal specimens were evaluated by phalloidin staining and immunohistochemical analysis using antibodies against Ki67, N-cadherin, and Na+/K+-ATPase. RESULTS Many more BrdU-positive cells were observed among the HCECs treated with ripasudil (0.3-30 μM) than among the control HCECs. Ripasudil-treated eyes in a rabbit model showed 91.5 ± 2.0% Ki67-positive cells after 48 hours, whereas control eyes showed 52.6 ± 1.3%. Five of six corneas became transparent in ripasudil-treated eyes, whereas zero of six corneas became transparent in the control eyes. Regenerated cell densities were higher in the eyes treated with ripasudil than in eyes treated with vehicle. Eyes treated with ripasudil expressed N-cadherin and Na+/K+-ATPase in almost all CECs, whereas this expression was decreased in control eyes. CONCLUSIONS Ripasudil promoted corneal endothelial wound healing, supporting its development as eye drops for treating acute corneal endothelial damage due to eye surgeries, especially cataract surgery.

  • Effect of the Rhoassociated kinase inhibitor eye drop (ripasudil) on corneal endothelial wound healing. Invest Ophthalmol Vis Sci.
    2016
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Nigel J Fullwood, Shigeru Kinoshita, Noriko Koizumi
    Abstract:

    PURPOSE. Ripasudil (Glanatec), a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved in Japan in September 2014 for the treatment of glaucoma and ocular hypertension. The purpose of this study was to investigate the effect of ripasudil eye drops on corneal endothelial morphology, as ROCK signaling is known to modulate the actin cytoskeleton. METHODS. Morphological changes in the corneal endothelium were evaluated in human subjects by specular and Slit-Lamp Microscopy, following topical administration of ripasudil. We also used a rabbit model to evaluate the effect of ripasudil on clinical parameters of the corneal endothelium. Twenty-four hours after ripasudil application, corneal specimens were evaluated by phalloidin staining, immunohistochemical analysis, and electron Microscopy. RESULTS. Specular Microscopy revealed morphological changes in human eyes, and Slit-Lamp Microscopy showed guttae-like findings. The rabbit model showed morphological changes similar to those seen in human eyes after ripasudil administration. Electron Microscopy demonstrated that these alterations are due to the formation of protrusions along the cell-cell borders, but this formation is transient. Expression of corneal endothelial function-related markers was not disrupted; corneal thickness and corneal volume were not changed; and no cell death was observed following ripasudil administration. CONCLUSIONS. Ripasudil induces transient guttae-like findings in humans, most likely due to protrusion formation along intracellular borders caused by the reduction in actomyosin contractility of the corneal endothelial cells. No severe adverse effects were observed. Physicians should be aware that ROCK inhibitors can cause these guttae-like findings, to avoid misdiagnosing patients as having Fuchs endothelial corneal dystrophy. (www.umin.ac.jp/ctr number, UMIN000018340.

  • Rho-associated kinase inhibitor eye drop (ripasudil) transiently alters the morphology of corneal endothelial cells.
    2016
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Shigeru Kinoshita, Noriko Koizumi, Kazuya Kakutani
    Abstract:

    PURPOSE. Ripasudil (Glanatec), a selective rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved as a glaucoma and ocular hypertension treatment in Japan in 2014. The purpose of this study was to investigate the feasibility of using ripasudil eye drops to treat corneal endothelial injuries. METHODS. Cultured human corneal endothelial cells (HCECs) were treated with ripasudil, and 5-bromo-2 0 -deoxyuridine (BrdU) incorporation was evaluated by ELISA. A rabbit corneal endothelial damage model was also created by mechanically scraping the corneal endothelium, followed by topical ripasudil eye drop application for 2 weeks. The anterior segment was evaluated by Slit-Lamp Microscopy, and central corneal thickness was measured by ultrasound pachymetry. Corneal specimens were evaluated by phalloidin staining and immunohistochemical analysis using antibodies against Ki67, N-cadherin, and Na RESULTS. Many more BrdU-positive cells were observed among the HCECs treated with ripasudil (0.3-30 lM) than among the control HCECs. Ripasudil-treated eyes in a rabbit model showed 91.5 6 2.0% Ki67-positive cells after 48 hours, whereas control eyes showed 52.6 6 1.3%. Five of six corneas became transparent in ripasudil-treated eyes, whereas zero of six corneas became transparent in the control eyes. Regenerated cell densities were higher in the eyes treated with ripasudil than in eyes treated with vehicle. Eyes treated with ripasudil expressed N-cadherin and Na þ /K þ -ATPase in almost all CECs, whereas this expression was decreased in control eyes. CONCLUSIONS. Ripasudil promoted corneal endothelial wound healing, supporting its development as eye drops for treating acute corneal endothelial damage due to eye surgeries, especially cataract surgery

  • rho associated kinase inhibitor eye drop ripasudil transiently alters the morphology of corneal endothelial cells
    Investigative Ophthalmology & Visual Science, 2015
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Nigel J Fullwood, Shigeru Kinoshita, Noriko Koizumi
    Abstract:

    PURPOSE: Ripasudil (Glanatec), a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved in Japan in September 2014 for the treatment of glaucoma and ocular hypertension. The purpose of this study was to investigate the effect of ripasudil eye drops on corneal endothelial morphology, as ROCK signaling is known to modulate the actin cytoskeleton. METHODS: Morphological changes in the corneal endothelium were evaluated in human subjects by specular and Slit-Lamp Microscopy, following topical administration of ripasudil. We also used a rabbit model to evaluate the effect of ripasudil on clinical parameters of the corneal endothelium. Twenty-four hours after ripasudil application, corneal specimens were evaluated by phalloidin staining, immunohistochemical analysis, and electron Microscopy. RESULTS: Specular Microscopy revealed morphological changes in human eyes, and Slit-Lamp Microscopy showed guttae-like findings. The rabbit model showed morphological changes similar to those seen in human eyes after ripasudil administration. Electron Microscopy demonstrated that these alterations are due to the formation of protrusions along the cell-cell borders, but this formation is transient. Expression of corneal endothelial function-related markers was not disrupted; corneal thickness and corneal volume were not changed; and no cell death was observed following ripasudil administration. CONCLUSIONS: Ripasudil induces transient guttae-like findings in humans, most likely due to protrusion formation along intracellular borders caused by the reduction in actomyosin contractility of the corneal endothelial cells. No severe adverse effects were observed. Physicians should be aware that ROCK inhibitors can cause these guttae-like findings, to avoid misdiagnosing patients as having Fuchs endothelial corneal dystrophy. (www.umin.ac.jp/ctr number, UMIN000018340.).

  • the rock inhibitor eye drop accelerates corneal endothelium wound healing
    Investigative Ophthalmology & Visual Science, 2013
    Co-Authors: Naoki Okumura, Noriko Koizumi, Eunduck P Kay, Morio Ueno, Yuji Sakamoto, Shinichiro Nakamura, Junji Hamuro, Shigeru Kinoshita
    Abstract:

    Purpose To evaluate the effect of Rho kinase (ROCK)-inhibitor eye drops on a corneal endothelial dysfunction primate model and human clinical case series of corneal endothelial dysfunction. Methods As a corneal-endothelial partially injured model, the corneal endothelium of seven cynomolgus monkeys was damaged by transcorneal freezing; 10 mm of rock inhibitor Y-27632 was then applied topically 6 times daily. The phenotype of the reconstructed corneal endothelium was evaluated by immunohistochemical analysis and noncontact specular Microscopy. For clinical study, the effect of Y-27632 eye drops after transcorneal freezing was evaluated in eight corneal endothelial dysfunction patients: four central corneal edema patients and four diffuse corneal edema patients. Results Slit-Lamp Microscopy revealed that both Y-27632-treated and -nontreated corneas became hazy after transcorneal freezing, and then recovered their transparency within 4 weeks. ROCK inhibitor Y-27632 promoted recovery of corneal endothelial cell density and wound healing in terms of both morphology and function. The percentage of ZO-1 and Na(+)/K(+)-ATPase positive cells in the regenerated area in the Y-27632 group was significantly higher than in the controls. Noncontact specular Microscopy revealed that corneal endothelial cell density was significantly higher in the Y-27632 group compared with the controls at 4 weeks; cell density reached approximately 3000 cells/mm(2), as opposed to 1500 cells/mm(2) in the control group. In addition to the animal study findings, the clinical study findings showed that Y-27632 eye drops effectively improved corneal edema of corneal endothelial dysfunction patients with central edema. Conclusions These findings show that rock inhibitor Y-27632 eye drops promote corneal endothelial wound healing in a primate animal model and suggest the possibility of Y-27632 as a novel therapeutic modality for certain forms of corneal endothelial dysfunction. (http://www.umin.ac.jp/ctr/ number, UMIN000003625.).

Naoki Okumura - One of the best experts on this subject based on the ideXlab platform.

  • effect of the rho associated kinase inhibitor eye drop ripasudil on corneal endothelial wound healing
    Investigative Ophthalmology & Visual Science, 2016
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Shigeru Kinoshita, Kazuya Kakutani, Noriko Koizumi
    Abstract:

    PURPOSE Ripasudil (Glanatec), a selective rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved as a glaucoma and ocular hypertension treatment in Japan in 2014. The purpose of this study was to investigate the feasibility of using ripasudil eye drops to treat corneal endothelial injuries. METHODS Cultured human corneal endothelial cells (HCECs) were treated with ripasudil, and 5-bromo-2'-deoxyuridine (BrdU) incorporation was evaluated by ELISA. A rabbit corneal endothelial damage model was also created by mechanically scraping the corneal endothelium, followed by topical ripasudil eye drop application for 2 weeks. The anterior segment was evaluated by Slit-Lamp Microscopy, and central corneal thickness was measured by ultrasound pachymetry. Corneal specimens were evaluated by phalloidin staining and immunohistochemical analysis using antibodies against Ki67, N-cadherin, and Na+/K+-ATPase. RESULTS Many more BrdU-positive cells were observed among the HCECs treated with ripasudil (0.3-30 μM) than among the control HCECs. Ripasudil-treated eyes in a rabbit model showed 91.5 ± 2.0% Ki67-positive cells after 48 hours, whereas control eyes showed 52.6 ± 1.3%. Five of six corneas became transparent in ripasudil-treated eyes, whereas zero of six corneas became transparent in the control eyes. Regenerated cell densities were higher in the eyes treated with ripasudil than in eyes treated with vehicle. Eyes treated with ripasudil expressed N-cadherin and Na+/K+-ATPase in almost all CECs, whereas this expression was decreased in control eyes. CONCLUSIONS Ripasudil promoted corneal endothelial wound healing, supporting its development as eye drops for treating acute corneal endothelial damage due to eye surgeries, especially cataract surgery.

  • Effect of the Rhoassociated kinase inhibitor eye drop (ripasudil) on corneal endothelial wound healing. Invest Ophthalmol Vis Sci.
    2016
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Nigel J Fullwood, Shigeru Kinoshita, Noriko Koizumi
    Abstract:

    PURPOSE. Ripasudil (Glanatec), a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved in Japan in September 2014 for the treatment of glaucoma and ocular hypertension. The purpose of this study was to investigate the effect of ripasudil eye drops on corneal endothelial morphology, as ROCK signaling is known to modulate the actin cytoskeleton. METHODS. Morphological changes in the corneal endothelium were evaluated in human subjects by specular and Slit-Lamp Microscopy, following topical administration of ripasudil. We also used a rabbit model to evaluate the effect of ripasudil on clinical parameters of the corneal endothelium. Twenty-four hours after ripasudil application, corneal specimens were evaluated by phalloidin staining, immunohistochemical analysis, and electron Microscopy. RESULTS. Specular Microscopy revealed morphological changes in human eyes, and Slit-Lamp Microscopy showed guttae-like findings. The rabbit model showed morphological changes similar to those seen in human eyes after ripasudil administration. Electron Microscopy demonstrated that these alterations are due to the formation of protrusions along the cell-cell borders, but this formation is transient. Expression of corneal endothelial function-related markers was not disrupted; corneal thickness and corneal volume were not changed; and no cell death was observed following ripasudil administration. CONCLUSIONS. Ripasudil induces transient guttae-like findings in humans, most likely due to protrusion formation along intracellular borders caused by the reduction in actomyosin contractility of the corneal endothelial cells. No severe adverse effects were observed. Physicians should be aware that ROCK inhibitors can cause these guttae-like findings, to avoid misdiagnosing patients as having Fuchs endothelial corneal dystrophy. (www.umin.ac.jp/ctr number, UMIN000018340.

  • Rho-associated kinase inhibitor eye drop (ripasudil) transiently alters the morphology of corneal endothelial cells.
    2016
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Shigeru Kinoshita, Noriko Koizumi, Kazuya Kakutani
    Abstract:

    PURPOSE. Ripasudil (Glanatec), a selective rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved as a glaucoma and ocular hypertension treatment in Japan in 2014. The purpose of this study was to investigate the feasibility of using ripasudil eye drops to treat corneal endothelial injuries. METHODS. Cultured human corneal endothelial cells (HCECs) were treated with ripasudil, and 5-bromo-2 0 -deoxyuridine (BrdU) incorporation was evaluated by ELISA. A rabbit corneal endothelial damage model was also created by mechanically scraping the corneal endothelium, followed by topical ripasudil eye drop application for 2 weeks. The anterior segment was evaluated by Slit-Lamp Microscopy, and central corneal thickness was measured by ultrasound pachymetry. Corneal specimens were evaluated by phalloidin staining and immunohistochemical analysis using antibodies against Ki67, N-cadherin, and Na RESULTS. Many more BrdU-positive cells were observed among the HCECs treated with ripasudil (0.3-30 lM) than among the control HCECs. Ripasudil-treated eyes in a rabbit model showed 91.5 6 2.0% Ki67-positive cells after 48 hours, whereas control eyes showed 52.6 6 1.3%. Five of six corneas became transparent in ripasudil-treated eyes, whereas zero of six corneas became transparent in the control eyes. Regenerated cell densities were higher in the eyes treated with ripasudil than in eyes treated with vehicle. Eyes treated with ripasudil expressed N-cadherin and Na þ /K þ -ATPase in almost all CECs, whereas this expression was decreased in control eyes. CONCLUSIONS. Ripasudil promoted corneal endothelial wound healing, supporting its development as eye drops for treating acute corneal endothelial damage due to eye surgeries, especially cataract surgery

  • rho associated kinase inhibitor eye drop ripasudil transiently alters the morphology of corneal endothelial cells
    Investigative Ophthalmology & Visual Science, 2015
    Co-Authors: Naoki Okumura, Yugo Okazaki, Ryota Inoue, Shinichiro Nakano, Nigel J Fullwood, Shigeru Kinoshita, Noriko Koizumi
    Abstract:

    PURPOSE: Ripasudil (Glanatec), a selective Rho-associated coiled coil-containing protein kinase (ROCK) inhibitor, was approved in Japan in September 2014 for the treatment of glaucoma and ocular hypertension. The purpose of this study was to investigate the effect of ripasudil eye drops on corneal endothelial morphology, as ROCK signaling is known to modulate the actin cytoskeleton. METHODS: Morphological changes in the corneal endothelium were evaluated in human subjects by specular and Slit-Lamp Microscopy, following topical administration of ripasudil. We also used a rabbit model to evaluate the effect of ripasudil on clinical parameters of the corneal endothelium. Twenty-four hours after ripasudil application, corneal specimens were evaluated by phalloidin staining, immunohistochemical analysis, and electron Microscopy. RESULTS: Specular Microscopy revealed morphological changes in human eyes, and Slit-Lamp Microscopy showed guttae-like findings. The rabbit model showed morphological changes similar to those seen in human eyes after ripasudil administration. Electron Microscopy demonstrated that these alterations are due to the formation of protrusions along the cell-cell borders, but this formation is transient. Expression of corneal endothelial function-related markers was not disrupted; corneal thickness and corneal volume were not changed; and no cell death was observed following ripasudil administration. CONCLUSIONS: Ripasudil induces transient guttae-like findings in humans, most likely due to protrusion formation along intracellular borders caused by the reduction in actomyosin contractility of the corneal endothelial cells. No severe adverse effects were observed. Physicians should be aware that ROCK inhibitors can cause these guttae-like findings, to avoid misdiagnosing patients as having Fuchs endothelial corneal dystrophy. (www.umin.ac.jp/ctr number, UMIN000018340.).

  • the rock inhibitor eye drop accelerates corneal endothelium wound healing
    Investigative Ophthalmology & Visual Science, 2013
    Co-Authors: Naoki Okumura, Noriko Koizumi, Eunduck P Kay, Morio Ueno, Yuji Sakamoto, Shinichiro Nakamura, Junji Hamuro, Shigeru Kinoshita
    Abstract:

    Purpose To evaluate the effect of Rho kinase (ROCK)-inhibitor eye drops on a corneal endothelial dysfunction primate model and human clinical case series of corneal endothelial dysfunction. Methods As a corneal-endothelial partially injured model, the corneal endothelium of seven cynomolgus monkeys was damaged by transcorneal freezing; 10 mm of rock inhibitor Y-27632 was then applied topically 6 times daily. The phenotype of the reconstructed corneal endothelium was evaluated by immunohistochemical analysis and noncontact specular Microscopy. For clinical study, the effect of Y-27632 eye drops after transcorneal freezing was evaluated in eight corneal endothelial dysfunction patients: four central corneal edema patients and four diffuse corneal edema patients. Results Slit-Lamp Microscopy revealed that both Y-27632-treated and -nontreated corneas became hazy after transcorneal freezing, and then recovered their transparency within 4 weeks. ROCK inhibitor Y-27632 promoted recovery of corneal endothelial cell density and wound healing in terms of both morphology and function. The percentage of ZO-1 and Na(+)/K(+)-ATPase positive cells in the regenerated area in the Y-27632 group was significantly higher than in the controls. Noncontact specular Microscopy revealed that corneal endothelial cell density was significantly higher in the Y-27632 group compared with the controls at 4 weeks; cell density reached approximately 3000 cells/mm(2), as opposed to 1500 cells/mm(2) in the control group. In addition to the animal study findings, the clinical study findings showed that Y-27632 eye drops effectively improved corneal edema of corneal endothelial dysfunction patients with central edema. Conclusions These findings show that rock inhibitor Y-27632 eye drops promote corneal endothelial wound healing in a primate animal model and suggest the possibility of Y-27632 as a novel therapeutic modality for certain forms of corneal endothelial dysfunction. (http://www.umin.ac.jp/ctr/ number, UMIN000003625.).

Jodhbir S Mehta - One of the best experts on this subject based on the ideXlab platform.

  • Biological corneal inlay for presbyopia derived from small incision lenticule extraction (SMILE)
    Nature Publishing Group, 2018
    Co-Authors: Yu-chi Liu, Ericia Pei Wen Teo, Heng Pei Ang, Xin Yi Seah, Nyein Chan Lwin, Gary Hin Fai Yam, Jodhbir S Mehta
    Abstract:

    Abstract Corneal inlays are a relatively new treatment option for presbyopia. Using biological inlays, derived from lenticules extracted from small incision lenticule extraction, may offer advantages over commercialized synthetic inlays in the aspect of biocompatibility. We conducted a non-human primate study to evaluate the safety, predictability, efficacy and tissue response after autogeneic, decellularized xenogeneic and xenogeneic lenticule implantation. The lenticule implantation effectively resulted in central corneal steepening (simulated keratometric values increased by 1.8–2.3 diopters), central hyper-prolate changes (asphericity Q values changed by −0.26 to −0.36), corneal anterior surface elevation (7.7–9.3 μm) and reasonable effective zone (1.5–1.8 times of the lenticule physical diameter), with no differences among the three groups. Slit Lamp Microscopy, transmission electron Microscopy, confocal Microscopy, histology and immunohistochemistry analyses confirmed the biocompatibility of the autogeneic and decellularized lenticules, whereas one eye in the xenogeneic group developed corneal stromal rejection during the study period. Our results showed that lenticule implantation has the potential for the management of presbyopia, and provide the basis for future clinical studies. The decellularization process may increase the potential utilization of lenticules without changing the efficacy

  • early corneal wound healing and inflammatory responses after refractive lenticule extraction relex
    Investigative Ophthalmology & Visual Science, 2011
    Co-Authors: Andri K Riau, Romesh I Angunawela, Shyam S Chaurasia, Wing Shan Lee, Donald T Tan, Jodhbir S Mehta
    Abstract:

    PURPOSE To compare the early corneal wound repair and inflammatory responses after refractive lenticule extraction (ReLEx) and LASIK. METHODS Eighteen rabbits underwent ReLEx and another 18 underwent LASIK. Each group was divided into three subgroups of six rabbits each and these were subjected to refractive corrections of -3.00 diopters (D), -6.00 D, and -9.00 D. Slit Lamp photography, anterior segment optical coherence tomography (AS-OCT), corneal topography, and in vivo confocal Microscopy were performed 1 day after surgery. After euthanatization, the corneas were subjected to immunofluorescent staining for fibronectin, CD11b, Ki-67, and TUNEL assay. RESULTS On Slit Lamp Microscopy, all corneas appeared clear pre- and postoperatively in both ReLEx and LASIK eyes. Corneal topography showed a more significant corneal flattening after LASIK than after ReLEx as the degree of correction was increased (P = 0.916 after -3.00 D correction to P = 0.097 after -9.00 D correction). In vivo confocal Microscopy showed less light-scattering particles at the flap interface after ReLEx compared with LASIK. Immunostaining of fibronectin showed a less abundant expression in corneas that underwent ReLEx than LASIK. The differences became more marked as the power of correction was increased. Similar trend was seen in the number of CD11b-positive cells (P = 0.476 after -3.00 D correction to P < 0.001 after -9.00D correction). There was no marked disparity observed in cell death and proliferation between post-ReLEx and -LASIK eyes. CONCLUSIONS This study has shown that the ReLEx procedure may result in less topographic changes, inflammation, and early extracellular matrix deposition than LASIK, especially at high refractive correction.

Yang Jiang - One of the best experts on this subject based on the ideXlab platform.

  • Tuck-in Lamellar keratoplasty with an lenticule obtained by small incision lenticule extraction for treatment of Post- LASIK Ectasia.
    Scientific reports, 2017
    Co-Authors: Yang Jiang, Shan Yang
    Abstract:

    Corneal ectasia is a rare but serious post-operative complication of LASIK. Our main aim was to describe and evaluate the efficacy and safety of tuck-in lamellar keratoplasty with an lenticule obtained by SMILE for treatment of Post LASIK Ectasia. Tuck-in lamellar keratoplasty was performed on three post-LASIK cornea ectasia patients (three eyes) with central corneal thickness less than 400 µm. Each patient was monitored for at least 12 months. Our primary outcomes measured pre and post-operatively included: Anterior segment optical coherence tomography(AS-OCT), corneal topography and monitored by Slit-Lamp Microscopy. The mean total corneal thickness preoperatively and 1 day, 1 month, 3 months and 12 months post-op were 360.00 ± 32.07 µm, 590.00 ± 10.00 µm, 536.67 ± 11.54 µm, 523.33 ± 37.85 µm, 466.67 ± 41.63 µm. The mean lenticule implanted 1 day, 1 month, 3 months and 12 months post-op were 173.33 ± 41.63 µm,136.67 ± 25.16 µm, 133.33 ± 40.41 µm, 130.00 ± 17.32 µm. There was no evidence of immune rejection or other complications. Tuck-in lamellar keratoplasty with an lenticule obtained by SMILE seems to be a safe and alternative surgical approach in the treatment of post - LASIK cornea ectasia, especially for severe cases with cornea thickness less than 400 μm.

  • a novel tectonic keratoplasty with femtosecond laser intrastromal lenticule for corneal ulcer and perforation
    Chinese Medical Journal, 2016
    Co-Authors: Yang Jiang, Xiao-wei Liu
    Abstract:

    Background: Small incision refractive lenticule extraction (SMILE) is an effective laser procedure that treats myopia. This research was to describe a novel approach to treat corneal ulcer or perforation using the corneal lenticules obtained from SMILE and to evaluate the safety and effectiveness of tectonic keratoplasty with femtosecond laser intrastromal lenticule (TEKIL). Methods: A total of twenty patients (22 eyes) were monitored for at least 6 months and were assessed using Slit Lamp Microscopy, optical coherence tomography, and best-corrected visual acuity (BCVA). Postoperative complications throughout the study period were recorded. Results: Corneal ulcer in 14 patients (16 eyes) and corneal perforation in six patients (6 eyes) were treated with TEKIL. The patients were ten females and ten males, with a mean age of 58.5 ± 16.3 years (range: 16–81 years). In this study, the most causes of corneal ulcer or perforation were immunologic causes (54.5%). After TEKIL procedure, global integrity was achieved in all cases. No immune rejection or perforation was detected. The mean BCVA improved from 0.17 ± 0.20 preoperatively to 0.27 ± 0.25 postoperatively at the final follow-up ( t = 2.095, P = 0.052). The postoperative BCVA improved in 12 eyes (54.5%) and maintained in nine eyes (40.9%). Vision function successfully maintained in all eyes (100%). In three cases, corneal ulcers were treated by reoperation of TEKIL at 3 months after the initial surgery for the reason that the residual corneal thickness was Conclusions: TEKIL seems to be an effective treatment for corneal ulcer and perforation in the condition of emergency and donor shortage.

  • A Novel Tectonic Keratoplasty with Femtosecond Laser Intrastromal Lenticule for Corneal Ulcer and Perforation
    Wolters Kluwer, 2016
    Co-Authors: Yang Jiang, Xiao-wei Liu
    Abstract:

    Background: Small incision refractive lenticule extraction (SMILE) is an effective laser procedure that treats myopia. This research was to describe a novel approach to treat corneal ulcer or perforation using the corneal lenticules obtained from SMILE and to evaluate the safety and effectiveness of tectonic keratoplasty with femtosecond laser intrastromal lenticule (TEKIL). Methods: A total of twenty patients (22 eyes) were monitored for at least 6 months and were assessed using Slit Lamp Microscopy, optical coherence tomography, and best-corrected visual acuity (BCVA). Postoperative complications throughout the study period were recorded. Results: Corneal ulcer in 14 patients (16 eyes) and corneal perforation in six patients (6 eyes) were treated with TEKIL. The patients were ten females and ten males, with a mean age of 58.5 ± 16.3 years (range: 16–81 years). In this study, the most causes of corneal ulcer or perforation were immunologic causes (54.5%). After TEKIL procedure, global integrity was achieved in all cases. No immune rejection or perforation was detected. The mean BCVA improved from 0.17 ± 0.20 preoperatively to 0.27 ± 0.25 postoperatively at the final follow-up (t = 2.095, P = 0.052). The postoperative BCVA improved in 12 eyes (54.5%) and maintained in nine eyes (40.9%). Vision function successfully maintained in all eyes (100%). In three cases, corneal ulcers were treated by reoperation of TEKIL at 3 months after the initial surgery for the reason that the residual corneal thickness was