Akihiro Ohira - Academia.edu (original) (raw)

Papers by Akihiro Ohira

Research paper thumbnail of Retinal Ischemia and Cell Proliferation in the Rat

Retina-the Journal of Retinal and Vitreous Diseases, 1990

Research paper thumbnail of Retinal ischemia and cell proliferation in the rat: the role of soluble mitogens

Graefes Archive for Clinical and Experimental Ophthalmology, Mar 1, 1990

Research paper thumbnail of Axonal protection by thioredoxin-1 with inhibition of interleukin-1β in TNF-induced optic nerve degeneration

Experimental Eye Research, Nov 1, 2016

Research paper thumbnail of Basic fibroblast growth factor stimulates 3H-thymidine uptake in retinal venular and capillary endothelial cells in vivo

PubMed, Jul 1, 1990

Recent studies have found basic fibroblast growth factor (bFGF), an angiogenic peptide, in retina... more Recent studies have found basic fibroblast growth factor (bFGF), an angiogenic peptide, in retina and have suggested that bFGF is responsible for retinal vascular proliferation. To test the hypothesis that bFGF stimulates 3H-thymidine uptake in retinal vascular cells in vivo, we injected bFGF (100 ng) into the vitreous cavity of six cats at 0 hr and again at 24 hr. Eight control eyes received boiled bFGF or no injection. After 46 hr, 3H-thymidine was injected into the vitreous cavity of all eyes and 2 hr later the eyes were enucleated. Intense 3H-thymidine uptake was seen in eyes with bFGF (56 +/- 20 SD positive cells per section) but not in control eyes (7-10 positive cells per section (P less than 0.001). Trypsin digest preparations showed that the thymidine uptake was predominantly in the venular (89%) and capillary (10%) endothelium and not in arterioles (1%) (P less than 0.001). The data suggest that retinal venular endothelial cells respond preferentially to exogenous bFGF, and in part may explain their prominent role in the neovascular process. In a second group of experiments to test the hypothesis that retinal ischemia releases a diffusable factor similar to bFGF that can cause 3H-thymidine uptake in retinal vascular cells, we created branch retinal vein occlusion in six cat eyes. The fellow eyes received no injections. In the eyes with branch vein occlusion there was an intense 3H-thymidine uptake within the distribution of the occluded vein (84 +/- 77 SD positive cells per section), but none in the areas outside the occluded vein (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Oxidative stress induces adult T cell leukemia derived factor/thioredoxin in the rat retina

PubMed, Feb 1, 1994

Background: Adult T cell leukemia derived factor (ADF), originally defined as an interleukin-2 re... more Background: Adult T cell leukemia derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin homolog. ADF/thioredoxin has several biologic functions, such as defense against cellular damage, activity to scavenge oxidative stress by hydrogen peroxide radicals and cytokine-like properties. We hypothesized that under certain conditions, ischemia followed by reperfusion and/or light exposure, ADF may be induced in the retina. Experimental design: To test this hypothesis, we prepared experimental animal models in which oxidative stress could be applied to the retina. In the present study, we examined ADF expression in the rat retina using temporary ischemia and reperfusion, and photodynamic retinal vascular thrombosis by immunohistochemical and Western blotting methods. Results: ADF expression was strongly induced in the retinal pigment epithelial cells after 2 hours of ischemia followed by 2, 24, or 48 hours of reperfusion. ADF was also expressed in retinal pigment epithelial cells as early as 3 hours after light exposure followed by rose bengal injection, and this expression increased with time. Western blotting data showed that ADF expression increased in the retinal pigment epithelial cells in the experimental group, as compared with the control group. These results indicate that ADF is actively induced in retinal pigment epithelial cells upon oxidative stress. Conclusions: ADF induction in retinal pigment epithelial cells may be involved in the defense mechanism against cellular damage caused by active oxygen species generated during oxygen stress to the retina.

Research paper thumbnail of Cytoprotective effect of thioredoxin against retinal photic injury in mice

PubMed, Apr 1, 2002

Purpose: To determine the protective role of thioredoxin (TRX), an endogenous redox (reduction an... more Purpose: To determine the protective role of thioredoxin (TRX), an endogenous redox (reduction and oxidation) regulator, against retinal photic injury in mice. Methods: Four-week-old BALB/c mice were exposed to white fluorescent light (8000 lux) for 2 hours. The number of both the photoreceptor cell nuclei and the TUNEL-positive photoreceptor cell nuclei were counted to determine the severity of damage. Expression of endogenous TRX was analyzed in the retinal samples by immunohistochemistry and Western blot. Recombinant (r)TRX or mutant rTRX, in which cysteines in the active site are replaced with serines, was injected intravitreously into BALB/c mice before light exposure. Oxidized and tyrosine-phosphorylated proteins were analyzed in retinal samples to examine the antioxidative effect of TRX. The number of photoreceptor cell nuclei and the DNA ladder in the retinal samples were analyzed. Results: A significant reduction was observed in the number of photoreceptor cells and induction of TUNEL-positive nuclei after light exposure. TRX expression was enhanced in both the neural retina and retinal pigment epithelium after light exposure. The amounts of oxidized and tyrosine-phosphorylated proteins decreased in the neural retinas of the rTRX-treated mice compared with the vehicle- or mutant rTRX-treated mice. The reduction of photoreceptor cells and formation of a DNA ladder were suppressed by rTRX pretreatment but not with mutant rTRX. Conclusions: TRX is induced in the retinal tissue after light exposure. Intraocular injection of rTRX suppresses photo-oxidative stress. TRX intensification may be a useful therapeutic strategy to prevent retinal photic injury.

Research paper thumbnail of Characterization of Glial Involvement in Proliferative Diabetic Retinopathy

Ophthalmologica, 1990

We studied the relationship of glial cells and other supporting tissues associated with newly for... more We studied the relationship of glial cells and other supporting tissues associated with newly formed blood vessels in proliferative diabetic retinopathy. Seventeen postmortem, freshly enucleated eyes from diabetic patients and 34 epiretinal and preretinal membranes removed during vitreous surgery for proliferative diabetic retinopathy were analyzed using the peroxidase-antiperoxidase method for light microscopy and protein A/gold labeling of ultrathin cryosections for transmission electron microscopy in addition to routine transmission and scanning electron microscopy. We found that glial cells are commonly and characteristically found in elevated diabetic proliferations and present at the vitreous surface. The newly formed blood vessels, however, were not seen at the edge of elevated epiretinal and preretinal membranes in early and intermediate stages. These results suggest that glial cells may extend beyond the vascularized areas of the proliferative tissue. It is possible that glial cells and their extracellular matrix contribute to the framework leading to the development of new blood vessels.

Research paper thumbnail of Change of redox status and modulation by thiol replenishment in retinal photooxidative damage

PubMed, Jul 1, 2002

Purpose: Cellular or tissue reduction-oxidation (redox) is crucial in various diseases. The prese... more Purpose: Cellular or tissue reduction-oxidation (redox) is crucial in various diseases. The present study was conducted to analyze how tissue redox status is affected by photooxidative stress and whether the exogenous thiol antioxidant N-acetylcysteine (NAC) affects photooxidative stress-induced retinal damage. Methods: Mice were intraperitoneally injected with either NAC (250 mg/kg) or phosphate-buffered saline (PBS) and exposed to white fluorescent light (8000 lux) for 2 hours. Levels of thioredoxin (TRX), glutaredoxin (GRX), and glutathione (GSH), endogenous regulators of redox; 4-hydroxy-2-nonenal (HNE)-modified protein, a marker of lipid peroxidation; and nuclear factor (NF)-kappaB, a redox-sensitive transcription factor in retinal samples, was measured by immunohistochemistry and Western blot or enzymatic recycling assay. Light-induced retinal damage estimated by electroretinography and quantitative immunohistochemistry for 8-hydroxy-2-deoxyguanosine (8OHdG index), a marker of oxidative stress-induced DNA damage, was compared in NAC- and PBS-treated mice. Results: Upregulation of TRX and HNE-modified protein, decrease of GSH, and nuclear translocation of NF-kappaB were noted after light exposure in PBS-treated mice. These changes were suppressed in NAC-treated mice compared with PBS-treated mice. GRX was not upregulated after light exposure in any mice. The a- and b-wave amplitudes were significantly higher, and the 8OHdG index was significantly lower after light exposure in NAC-treated mice than in PBS-treated mice. Conclusions: Retinal redox status is altered by intense light and is normalized partially by the effect of NAC on TRX and GSH tissue levels. Manipulation of the tissue redox state by exogenous thiol replenishment may be a useful strategy to prevent retinal photooxidative damage.

Research paper thumbnail of Attenuation of retinal photooxidative damage in thioredoxin transgenic mice

Neuroscience Letters, Jun 1, 2002

Research paper thumbnail of Enhanced Oxidative Stress and Impaired Thioredoxin Expression in Spontaneously Hypertensive Rats

Antioxidants & Redox Signaling, Feb 1, 2004

As oxidative stress plays a crucial role in the development and pathogenesis of hypertension, we ... more As oxidative stress plays a crucial role in the development and pathogenesis of hypertension, we analyzed the redox (reduction/oxidation) status in tissues from Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP). Expressions of 8-hydroxy-2'-deoxyguanosine, a marker for oxidative stress-induced DNA damage, and protein carbonylation, a marker for oxidation status of proteins, were enhanced in aorta, heart, and kidney from SHR and SHRSP compared with WKY. The expression of redox regulating protein, thioredoxin (TRX), estimated by immunohistochemistry and western blot, and expression of TRX gene estimated by real-time RT-PCR were markedly suppressed in those tissues from SHR and SHRSP compared with WKY. Induction of TRX was impaired after angiotension II treatment in peripheral blood mononuclear cells isolated from SHR and SHRSP compared with those isolated from WKY. Although previous reports have shown that TRX is induced by a variety of oxidative stress in tissues, the present study shows the impaired induction of TRX in tissues from genetically hypertensive rats despite the relative increment of oxidative stress. Redox imbalance in essential organs may play a crucial role in the development and pathogenesis of hypertension.

Research paper thumbnail of Cytoprotective Effect of Thioredoxin against Retinal Light Damage in Mice

Investigative Ophthalmology & Visual Science, Dec 1, 2002

Research paper thumbnail of Topical Dexamethasone gamma-Cyclodextrin Nanoparticle Eye Drops increase Visual Acuity and decrease Macular Thickness in Diabetic Macular Edema

Investigative Ophthalmology & Visual Science, Jun 11, 2015

Purpose: To test the efficacy and safety of topical 1.5% dexamethasone γ-cyclodextrin nanoparticl... more Purpose: To test the efficacy and safety of topical 1.5% dexamethasone γ-cyclodextrin nanoparticle eye drops (dexNP) for diabetic macular edema (DME) and compare to posterior subtenon injection of ...

Research paper thumbnail of Thioredoxin Gene Expression in Rat Knee Articular Cartilage After Full-Thickness Injury

Connective Tissue Research, 2005

To study the expression of the antioxidative protein thioredoxin (TRX) in intact and injured arti... more To study the expression of the antioxidative protein thioredoxin (TRX) in intact and injured articular cartilage, we examined the presence of trx mRNA in rat knee joints by in situ hybridization. Our results showed that in the intact knee, most cells, including articular cartilage chondrocytes, expressed trx mRNA. We examined joints at 1, 7, 14, and 28 days after the infliction of full-thickness cartilage injuries on distal femoral condyles. At 1 day after injury, no significant changes were observed in the wound or in trx expression pattern. However, at 7 to 28 days after injury, the wound became filled with repair tissue. Also, trx expression was detected in differentiating mesenchymal cells in the deeper zones of the wound but not in fibroblast-like cells in the upper part of the repair tissue, toward the joint cavity. This lack of TRX expression in the fibroblast-like cells may underlie the susceptibility of the repair tissue fibrocartilage to oxidative stress.

Research paper thumbnail of Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina

Research paper thumbnail of Treatment of non‐infectious ophthalmic inflammatory diseases with 1.5% dexamethasone γ ‐cyclodextrin nanoparticle eye drops

Acta Ophthalmologica, 2019

Research paper thumbnail of Induction of Thioredoxin via Antioxidant Responsive Element, and Attenuation of Retinal Light Damage in Mice by Sulforaphane

Investigative Ophthalmology & Visual Science, 2005

Research paper thumbnail of Structural and Functional Change in Albino Rat Retina Induced by Various Visible Light Wavelengths

International Journal of Molecular Sciences, 2021

The effects of visible light, from short to long wavelengths, on the retina were investigated fun... more The effects of visible light, from short to long wavelengths, on the retina were investigated functionally and histologically. The left eyes of Sprague–Dawley albino rats (6-weeks old, n = 6 for each wavelength) were exposed to seven narrow-band wavelengths (central wavelengths, 421, 441, 459, 501, 541, 581, and 615 nm) with bandwidths of 16 to 29 nm (half bandwidth, ±8–14.5 nm) using a xenon lamp source with bandpass filters at the retinal radiant exposures of 340 and 680 J/cm2. The right unexposed eyes served as controls. Seven days after exposure, flash electroretinograms (ERGs) were recorded, and the outer nuclear layer (ONL) thickness was measured. Compared to the unexposed eyes, significant reductions in the a- and b-wave ERG amplitudes were seen in eyes exposed to 460-nm or shorter wavelengths of light. The ONL thickness near the optic nerve head also tended to decrease with exposure to shorter wavelengths. The decreased ERG amplitudes and ONL thicknesses were most prominent ...

Research paper thumbnail of Mitochondrial induction of adult T cell leukemia derived factor (ADF/hTx) after oxidative stresses in retinal pigment epithelial cells

Adult T cell leukemia derived factor (ADF) is a human homologue of thioredoxin (hTx), which exhib... more Adult T cell leukemia derived factor (ADF) is a human homologue of thioredoxin (hTx), which exhibits scavenging activity with reactive oxygen intermediates. In their previous study, the authors found that after transient retinal ischemia, the expression of thioredoxin in rat retinal pigment epithelium (RPE) layer increased markedly. The present investigation is to determine intracellular ADF localization in RPE after transient ischemia and in cultured human RPE cells after oxidative insult by H2O2. The authors employed immunoelectron microscopy to examine ADF localization in RPE. Labeling density analysis was performed to supplement the main observation in the experiment of transient retinal ischemia. 3-(4,5-dimethylthiazol-2yl)-2-5-diphenyltetrazolium bromide (MTT) assay was performed to verify the protective role of recombinant ADF (rADF) against H2O2. In immunogold electron microscopy, sparse ADF-positive labeling was seen in the cytosol and mitochondria in normal rat RPE and in untreated cultured RPE cells. After oxidative stress, it was concentrated in mitochondria in both groups. MTT assay proved that rADF protected cultured RPE from the toxicity of H2O2. This study shows the induction of ADF/hTx in mitochondria of RPE after oxidative stresses and its protective effect on cultured RPE exposed to H2O2. The data indicate the possibly important role of ADF/hTx in the protection of retinal cells from the oxidative stresses associated with retinal ischemic disease and probably with regular visual activity.

Research paper thumbnail of Improving efficiency through analysis of data obtained from an RFID tag system for surgical instruments

2015 IEEE 5th International Conference on Consumer Electronics - Berlin (ICCE-Berlin), 2015

The number of surgical instruments that must be managed can be up to 100 for a single operation. ... more The number of surgical instruments that must be managed can be up to 100 for a single operation. Careful counting before and after an operation and proper identification of each instrument being stored in a container after sterilization are indispensable to patient safety. In the past this has required a great amount of hand labor. To improve efficiency, Shimane University Hospital introduced a system called SIMSAFE that uses RFID tags. The data obtained promotes effective and efficient instrument management. This paper introduces the management of surgical instruments when using SIMSAFE and shows the results of a preliminary data analysis.

Research paper thumbnail of Retinal risks of high-dose ornithine supplements: a review

British Journal of Nutrition, 2011

We reviewed the literature on ornithine supplementation and related topics. Nutritionists and phy... more We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful. Paediatricians and biochemists have reported that ornithine is supplemented for NH3 detoxification in the hyperornithinaemia–hyperammonaemia–homocitrullinuria (HHH) syndrome. In contrast, ophthalmic researchers have reported retinotoxicity associated with high-dose ornithine. In vivo and in vitro experiments have shown that high concentrations of ornithine or its metabolites are toxic to the retinal pigment epithelial (RPE) cells. Long-term (exceeding a few years) and high concentrations (exceeding 600 μmol/l) of ornithine in the blood induce retinal toxicity in gyrate atrophy of the choroid and retina (GA). Intermittent high levels of ornithine do not lead to retinal lesions. Constant blood ornithine levels between 250 and 600 μmol/l do not induce retinal lesions or cause a very slowly progressive retinal degeneration. Bloo...

Research paper thumbnail of Retinal Ischemia and Cell Proliferation in the Rat

Retina-the Journal of Retinal and Vitreous Diseases, 1990

Research paper thumbnail of Retinal ischemia and cell proliferation in the rat: the role of soluble mitogens

Graefes Archive for Clinical and Experimental Ophthalmology, Mar 1, 1990

Research paper thumbnail of Axonal protection by thioredoxin-1 with inhibition of interleukin-1β in TNF-induced optic nerve degeneration

Experimental Eye Research, Nov 1, 2016

Research paper thumbnail of Basic fibroblast growth factor stimulates 3H-thymidine uptake in retinal venular and capillary endothelial cells in vivo

PubMed, Jul 1, 1990

Recent studies have found basic fibroblast growth factor (bFGF), an angiogenic peptide, in retina... more Recent studies have found basic fibroblast growth factor (bFGF), an angiogenic peptide, in retina and have suggested that bFGF is responsible for retinal vascular proliferation. To test the hypothesis that bFGF stimulates 3H-thymidine uptake in retinal vascular cells in vivo, we injected bFGF (100 ng) into the vitreous cavity of six cats at 0 hr and again at 24 hr. Eight control eyes received boiled bFGF or no injection. After 46 hr, 3H-thymidine was injected into the vitreous cavity of all eyes and 2 hr later the eyes were enucleated. Intense 3H-thymidine uptake was seen in eyes with bFGF (56 +/- 20 SD positive cells per section) but not in control eyes (7-10 positive cells per section (P less than 0.001). Trypsin digest preparations showed that the thymidine uptake was predominantly in the venular (89%) and capillary (10%) endothelium and not in arterioles (1%) (P less than 0.001). The data suggest that retinal venular endothelial cells respond preferentially to exogenous bFGF, and in part may explain their prominent role in the neovascular process. In a second group of experiments to test the hypothesis that retinal ischemia releases a diffusable factor similar to bFGF that can cause 3H-thymidine uptake in retinal vascular cells, we created branch retinal vein occlusion in six cat eyes. The fellow eyes received no injections. In the eyes with branch vein occlusion there was an intense 3H-thymidine uptake within the distribution of the occluded vein (84 +/- 77 SD positive cells per section), but none in the areas outside the occluded vein (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Oxidative stress induces adult T cell leukemia derived factor/thioredoxin in the rat retina

PubMed, Feb 1, 1994

Background: Adult T cell leukemia derived factor (ADF), originally defined as an interleukin-2 re... more Background: Adult T cell leukemia derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin homolog. ADF/thioredoxin has several biologic functions, such as defense against cellular damage, activity to scavenge oxidative stress by hydrogen peroxide radicals and cytokine-like properties. We hypothesized that under certain conditions, ischemia followed by reperfusion and/or light exposure, ADF may be induced in the retina. Experimental design: To test this hypothesis, we prepared experimental animal models in which oxidative stress could be applied to the retina. In the present study, we examined ADF expression in the rat retina using temporary ischemia and reperfusion, and photodynamic retinal vascular thrombosis by immunohistochemical and Western blotting methods. Results: ADF expression was strongly induced in the retinal pigment epithelial cells after 2 hours of ischemia followed by 2, 24, or 48 hours of reperfusion. ADF was also expressed in retinal pigment epithelial cells as early as 3 hours after light exposure followed by rose bengal injection, and this expression increased with time. Western blotting data showed that ADF expression increased in the retinal pigment epithelial cells in the experimental group, as compared with the control group. These results indicate that ADF is actively induced in retinal pigment epithelial cells upon oxidative stress. Conclusions: ADF induction in retinal pigment epithelial cells may be involved in the defense mechanism against cellular damage caused by active oxygen species generated during oxygen stress to the retina.

Research paper thumbnail of Cytoprotective effect of thioredoxin against retinal photic injury in mice

PubMed, Apr 1, 2002

Purpose: To determine the protective role of thioredoxin (TRX), an endogenous redox (reduction an... more Purpose: To determine the protective role of thioredoxin (TRX), an endogenous redox (reduction and oxidation) regulator, against retinal photic injury in mice. Methods: Four-week-old BALB/c mice were exposed to white fluorescent light (8000 lux) for 2 hours. The number of both the photoreceptor cell nuclei and the TUNEL-positive photoreceptor cell nuclei were counted to determine the severity of damage. Expression of endogenous TRX was analyzed in the retinal samples by immunohistochemistry and Western blot. Recombinant (r)TRX or mutant rTRX, in which cysteines in the active site are replaced with serines, was injected intravitreously into BALB/c mice before light exposure. Oxidized and tyrosine-phosphorylated proteins were analyzed in retinal samples to examine the antioxidative effect of TRX. The number of photoreceptor cell nuclei and the DNA ladder in the retinal samples were analyzed. Results: A significant reduction was observed in the number of photoreceptor cells and induction of TUNEL-positive nuclei after light exposure. TRX expression was enhanced in both the neural retina and retinal pigment epithelium after light exposure. The amounts of oxidized and tyrosine-phosphorylated proteins decreased in the neural retinas of the rTRX-treated mice compared with the vehicle- or mutant rTRX-treated mice. The reduction of photoreceptor cells and formation of a DNA ladder were suppressed by rTRX pretreatment but not with mutant rTRX. Conclusions: TRX is induced in the retinal tissue after light exposure. Intraocular injection of rTRX suppresses photo-oxidative stress. TRX intensification may be a useful therapeutic strategy to prevent retinal photic injury.

Research paper thumbnail of Characterization of Glial Involvement in Proliferative Diabetic Retinopathy

Ophthalmologica, 1990

We studied the relationship of glial cells and other supporting tissues associated with newly for... more We studied the relationship of glial cells and other supporting tissues associated with newly formed blood vessels in proliferative diabetic retinopathy. Seventeen postmortem, freshly enucleated eyes from diabetic patients and 34 epiretinal and preretinal membranes removed during vitreous surgery for proliferative diabetic retinopathy were analyzed using the peroxidase-antiperoxidase method for light microscopy and protein A/gold labeling of ultrathin cryosections for transmission electron microscopy in addition to routine transmission and scanning electron microscopy. We found that glial cells are commonly and characteristically found in elevated diabetic proliferations and present at the vitreous surface. The newly formed blood vessels, however, were not seen at the edge of elevated epiretinal and preretinal membranes in early and intermediate stages. These results suggest that glial cells may extend beyond the vascularized areas of the proliferative tissue. It is possible that glial cells and their extracellular matrix contribute to the framework leading to the development of new blood vessels.

Research paper thumbnail of Change of redox status and modulation by thiol replenishment in retinal photooxidative damage

PubMed, Jul 1, 2002

Purpose: Cellular or tissue reduction-oxidation (redox) is crucial in various diseases. The prese... more Purpose: Cellular or tissue reduction-oxidation (redox) is crucial in various diseases. The present study was conducted to analyze how tissue redox status is affected by photooxidative stress and whether the exogenous thiol antioxidant N-acetylcysteine (NAC) affects photooxidative stress-induced retinal damage. Methods: Mice were intraperitoneally injected with either NAC (250 mg/kg) or phosphate-buffered saline (PBS) and exposed to white fluorescent light (8000 lux) for 2 hours. Levels of thioredoxin (TRX), glutaredoxin (GRX), and glutathione (GSH), endogenous regulators of redox; 4-hydroxy-2-nonenal (HNE)-modified protein, a marker of lipid peroxidation; and nuclear factor (NF)-kappaB, a redox-sensitive transcription factor in retinal samples, was measured by immunohistochemistry and Western blot or enzymatic recycling assay. Light-induced retinal damage estimated by electroretinography and quantitative immunohistochemistry for 8-hydroxy-2-deoxyguanosine (8OHdG index), a marker of oxidative stress-induced DNA damage, was compared in NAC- and PBS-treated mice. Results: Upregulation of TRX and HNE-modified protein, decrease of GSH, and nuclear translocation of NF-kappaB were noted after light exposure in PBS-treated mice. These changes were suppressed in NAC-treated mice compared with PBS-treated mice. GRX was not upregulated after light exposure in any mice. The a- and b-wave amplitudes were significantly higher, and the 8OHdG index was significantly lower after light exposure in NAC-treated mice than in PBS-treated mice. Conclusions: Retinal redox status is altered by intense light and is normalized partially by the effect of NAC on TRX and GSH tissue levels. Manipulation of the tissue redox state by exogenous thiol replenishment may be a useful strategy to prevent retinal photooxidative damage.

Research paper thumbnail of Attenuation of retinal photooxidative damage in thioredoxin transgenic mice

Neuroscience Letters, Jun 1, 2002

Research paper thumbnail of Enhanced Oxidative Stress and Impaired Thioredoxin Expression in Spontaneously Hypertensive Rats

Antioxidants & Redox Signaling, Feb 1, 2004

As oxidative stress plays a crucial role in the development and pathogenesis of hypertension, we ... more As oxidative stress plays a crucial role in the development and pathogenesis of hypertension, we analyzed the redox (reduction/oxidation) status in tissues from Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), and stroke-prone SHR (SHRSP). Expressions of 8-hydroxy-2'-deoxyguanosine, a marker for oxidative stress-induced DNA damage, and protein carbonylation, a marker for oxidation status of proteins, were enhanced in aorta, heart, and kidney from SHR and SHRSP compared with WKY. The expression of redox regulating protein, thioredoxin (TRX), estimated by immunohistochemistry and western blot, and expression of TRX gene estimated by real-time RT-PCR were markedly suppressed in those tissues from SHR and SHRSP compared with WKY. Induction of TRX was impaired after angiotension II treatment in peripheral blood mononuclear cells isolated from SHR and SHRSP compared with those isolated from WKY. Although previous reports have shown that TRX is induced by a variety of oxidative stress in tissues, the present study shows the impaired induction of TRX in tissues from genetically hypertensive rats despite the relative increment of oxidative stress. Redox imbalance in essential organs may play a crucial role in the development and pathogenesis of hypertension.

Research paper thumbnail of Cytoprotective Effect of Thioredoxin against Retinal Light Damage in Mice

Investigative Ophthalmology & Visual Science, Dec 1, 2002

Research paper thumbnail of Topical Dexamethasone gamma-Cyclodextrin Nanoparticle Eye Drops increase Visual Acuity and decrease Macular Thickness in Diabetic Macular Edema

Investigative Ophthalmology & Visual Science, Jun 11, 2015

Purpose: To test the efficacy and safety of topical 1.5% dexamethasone γ-cyclodextrin nanoparticl... more Purpose: To test the efficacy and safety of topical 1.5% dexamethasone γ-cyclodextrin nanoparticle eye drops (dexNP) for diabetic macular edema (DME) and compare to posterior subtenon injection of ...

Research paper thumbnail of Thioredoxin Gene Expression in Rat Knee Articular Cartilage After Full-Thickness Injury

Connective Tissue Research, 2005

To study the expression of the antioxidative protein thioredoxin (TRX) in intact and injured arti... more To study the expression of the antioxidative protein thioredoxin (TRX) in intact and injured articular cartilage, we examined the presence of trx mRNA in rat knee joints by in situ hybridization. Our results showed that in the intact knee, most cells, including articular cartilage chondrocytes, expressed trx mRNA. We examined joints at 1, 7, 14, and 28 days after the infliction of full-thickness cartilage injuries on distal femoral condyles. At 1 day after injury, no significant changes were observed in the wound or in trx expression pattern. However, at 7 to 28 days after injury, the wound became filled with repair tissue. Also, trx expression was detected in differentiating mesenchymal cells in the deeper zones of the wound but not in fibroblast-like cells in the upper part of the repair tissue, toward the joint cavity. This lack of TRX expression in the fibroblast-like cells may underlie the susceptibility of the repair tissue fibrocartilage to oxidative stress.

Research paper thumbnail of Protective Effect of Highly Polymeric A-Type Proanthocyanidins from Seed Shells of Japanese Horse Chestnut (Aesculus turbinata BLUME) against Light-Induced Oxidative Damage in Rat Retina

Research paper thumbnail of Treatment of non‐infectious ophthalmic inflammatory diseases with 1.5% dexamethasone γ ‐cyclodextrin nanoparticle eye drops

Acta Ophthalmologica, 2019

Research paper thumbnail of Induction of Thioredoxin via Antioxidant Responsive Element, and Attenuation of Retinal Light Damage in Mice by Sulforaphane

Investigative Ophthalmology & Visual Science, 2005

Research paper thumbnail of Structural and Functional Change in Albino Rat Retina Induced by Various Visible Light Wavelengths

International Journal of Molecular Sciences, 2021

The effects of visible light, from short to long wavelengths, on the retina were investigated fun... more The effects of visible light, from short to long wavelengths, on the retina were investigated functionally and histologically. The left eyes of Sprague–Dawley albino rats (6-weeks old, n = 6 for each wavelength) were exposed to seven narrow-band wavelengths (central wavelengths, 421, 441, 459, 501, 541, 581, and 615 nm) with bandwidths of 16 to 29 nm (half bandwidth, ±8–14.5 nm) using a xenon lamp source with bandpass filters at the retinal radiant exposures of 340 and 680 J/cm2. The right unexposed eyes served as controls. Seven days after exposure, flash electroretinograms (ERGs) were recorded, and the outer nuclear layer (ONL) thickness was measured. Compared to the unexposed eyes, significant reductions in the a- and b-wave ERG amplitudes were seen in eyes exposed to 460-nm or shorter wavelengths of light. The ONL thickness near the optic nerve head also tended to decrease with exposure to shorter wavelengths. The decreased ERG amplitudes and ONL thicknesses were most prominent ...

Research paper thumbnail of Mitochondrial induction of adult T cell leukemia derived factor (ADF/hTx) after oxidative stresses in retinal pigment epithelial cells

Adult T cell leukemia derived factor (ADF) is a human homologue of thioredoxin (hTx), which exhib... more Adult T cell leukemia derived factor (ADF) is a human homologue of thioredoxin (hTx), which exhibits scavenging activity with reactive oxygen intermediates. In their previous study, the authors found that after transient retinal ischemia, the expression of thioredoxin in rat retinal pigment epithelium (RPE) layer increased markedly. The present investigation is to determine intracellular ADF localization in RPE after transient ischemia and in cultured human RPE cells after oxidative insult by H2O2. The authors employed immunoelectron microscopy to examine ADF localization in RPE. Labeling density analysis was performed to supplement the main observation in the experiment of transient retinal ischemia. 3-(4,5-dimethylthiazol-2yl)-2-5-diphenyltetrazolium bromide (MTT) assay was performed to verify the protective role of recombinant ADF (rADF) against H2O2. In immunogold electron microscopy, sparse ADF-positive labeling was seen in the cytosol and mitochondria in normal rat RPE and in untreated cultured RPE cells. After oxidative stress, it was concentrated in mitochondria in both groups. MTT assay proved that rADF protected cultured RPE from the toxicity of H2O2. This study shows the induction of ADF/hTx in mitochondria of RPE after oxidative stresses and its protective effect on cultured RPE exposed to H2O2. The data indicate the possibly important role of ADF/hTx in the protection of retinal cells from the oxidative stresses associated with retinal ischemic disease and probably with regular visual activity.

Research paper thumbnail of Improving efficiency through analysis of data obtained from an RFID tag system for surgical instruments

2015 IEEE 5th International Conference on Consumer Electronics - Berlin (ICCE-Berlin), 2015

The number of surgical instruments that must be managed can be up to 100 for a single operation. ... more The number of surgical instruments that must be managed can be up to 100 for a single operation. Careful counting before and after an operation and proper identification of each instrument being stored in a container after sterilization are indispensable to patient safety. In the past this has required a great amount of hand labor. To improve efficiency, Shimane University Hospital introduced a system called SIMSAFE that uses RFID tags. The data obtained promotes effective and efficient instrument management. This paper introduces the management of surgical instruments when using SIMSAFE and shows the results of a preliminary data analysis.

Research paper thumbnail of Retinal risks of high-dose ornithine supplements: a review

British Journal of Nutrition, 2011

We reviewed the literature on ornithine supplementation and related topics. Nutritionists and phy... more We reviewed the literature on ornithine supplementation and related topics. Nutritionists and physicians have reported that ornithine supplementation is useful. Paediatricians and biochemists have reported that ornithine is supplemented for NH3 detoxification in the hyperornithinaemia–hyperammonaemia–homocitrullinuria (HHH) syndrome. In contrast, ophthalmic researchers have reported retinotoxicity associated with high-dose ornithine. In vivo and in vitro experiments have shown that high concentrations of ornithine or its metabolites are toxic to the retinal pigment epithelial (RPE) cells. Long-term (exceeding a few years) and high concentrations (exceeding 600 μmol/l) of ornithine in the blood induce retinal toxicity in gyrate atrophy of the choroid and retina (GA). Intermittent high levels of ornithine do not lead to retinal lesions. Constant blood ornithine levels between 250 and 600 μmol/l do not induce retinal lesions or cause a very slowly progressive retinal degeneration. Bloo...