Toshiyuki Oshitari

National Center for Global Health and Medicine in Japan, Japan

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Publications (68)92.17 Total impact

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    ABSTRACT: The study was conducted to determine whether serum vascular endothelial growth factor (VEGF) levels are significantly correlated with subfoveal choroidal thickness (CT) and foveal thickness (FT) in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome.
    11/2014;
  • Takayuki Baba, Toshiyuki Oshitari, Shuichi Yamamoto
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    ABSTRACT: Alpha-B crystallin (αB-crystallin) is a molecular chaperone, and one of the small heat shock proteins (sHSPs). αB-crystallin has been shown to have neuroprotective properties. The purpose of this study was to determine the level of αB-crystallin in eyes with a rhegmatogenous retinal detachment (RRD).
    10/2014;
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    ABSTRACT: We report a case of unilateral blindness due to ophthalmic artery occlusion following injection of hyaluronic acid into the glabellar area for facial soft-tissue augmentation.
    Nippon Ganka Gakkai zasshi 09/2014; 118(9):783-7.
  • G Bikbova, T Oshitari, S Yamamoto
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    ABSTRACT: Purpose To determine the effect of high doses of AGEs on neurite regeneration in isolated rat retinas, and the regenerative effects of different neurotrophic factors.Methods Retinal explants of 4 adult SD rats were three-dimensionally cultured in collagen gel, and incubated in: 1) serum free control culture media; 2) 100 μg/ml glucose-AGE-BSA, glycolaldehyde-AGE-BSA, glyceraldehyde-AGE-BSA media; 3) glucose, glycol, glycer+100 ng/ml neurotrophin 4 (NT-4)media; 4) glucose, glycol, glycer+100 ng/ml hepatocyte growth factor (HGF) media; 5)glucose, glycol, glycer+100 ng/ml glial cell line derived neurotrophic factor (GDNF) media; or 6) glucose, glycol, glycer+100 ng/ml tauroursodeoxycholic acid (TUDCA) media. After 7 days, the number of regenerating neurites were counted under a phase-contrast microscope. The explants were immunostained for NFkB transcription factor. Statistical analyses were performed by one-way ANOVA.Results In retinas incubated with AGEs, the number of regenerating neurites were fewer than in control. Neurotrophic factors increased the number of neurites, but more significantly in the NT4 group. The number of NFkB immunopositive cells was higher in retinas exposed to AGEs than in control (53,2 ± 7,2% vs.31,6 ± 16,08%,P = 0,0146). Neurotrophic factors decreased the number of immunopositives cell, but more significantly in the NT4 group.Conclusion High dose AGEs induce activation of NFkB and NT4 significantly suppresses this activation and enhances neurite regeneration in isolated retinas compared with other neurotrophic factors such as HGF,GDNF,and TUDCA.
    Acta ophthalmologica 09/2014; 92(s253). · 2.44 Impact Factor
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    ABSTRACT: Diabetes mellitus is a disease with a devastating impact on population. Recent data revealed that early retinal neuropathy in patients with diabetic retinopathy involved a reduced expression of brain-derived neurotrophic factor. Retinal ganglion cells (RGC) neuropathy is a progressive optic nerve neuropathy with RGC death and axonal degeneration, and it leads to blindness in the elderly population worldwide. Thus, neuroprotective therapies that rescue damaged RGCs and inhibit the progression of RGC loss and axonal degeneration are needed. This review introduces potential neuroprotective therapies using different neurotrophic factors for damaged RGC in eyes with RGC neuropathy associated diseases.
    Current diabetes reviews 05/2014;
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    Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
    Neural Regeneration Research 03/2014; 7(10):701-702. · 0.14 Impact Factor
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    ABSTRACT: To present our findings in a case of Werner syndrome with refractory cystoid macular edema (CME) and to determine the expression and the distribution of WRN proteins in human retinas. A 35-year-old man with Werner syndrome who developed CME after YAG laser treatment was studied. Optical coherence tomographic (OCT) scans were used to examine the CME in the right eye. The patient received topical eye drops (0.1% bromfenac sodium hydrate twice daily and 1% dorzolamide hydrochloride thrice daily), sub-Tenon triamcinolone injection thrice, intravitreal bevacizumab injection twice, and pars plana vitrectomy of the right eye. Genetic analyses were performed to diagnose the disease. To examine the expression and distribution of WRN proteins in the retinas, immunohistochemistry for WRN proteins was performed in human retinas. The CME in the right eye was not improved by any of the treatments. During the follow-up period, CME developed in the left eye. Genetic analyses detected compound heterozygosity, Mut4 and Mut11, in the WRN gene and the individual was diagnosed with Werner syndrome. Immunohistochemical analysis of WRN proteins expression in human retinas showed that WRN proteins were expressed in the parts of the Muller cells in the inner nuclear layer and outer nuclear layer. Patients with Werner syndrome can develop severe CME after laser treatment. A pathological link may exist between mutations in the WRN gene and the development of CME in patients with Werner syndrome.
    BMC Ophthalmology 03/2014; 14(1):31. · 1.44 Impact Factor
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    ABSTRACT: Abstract Purpose: Vascular endothelial growth factor 165b (VEGF165b) is a splice variant of VEGF-A and is an anti-angiogenic form as opposed to a pro-angiogenic form of VEGF. We compared the level of VEGF165b in the aqueous humor of 77 eyes with exudative age-related macular degeneration (AMD) and 38 eyes with retinal vein occlusion (RVO). Design: A prospective, interventional case series. Methods: The concentration of aqueous VEGF165b was measured by enzyme-linked immunosorbent assay (ELISA), and its level in the subgroups of AMD, classic and occult choroidal neovascularization (CNV) and polypoidal choroidal vasculopathy (PCV), was compared. The relationships between the VEGF165b level and the greatest linear dimension (GLD), central foveal thickness (CFT), and the height of the subretinal fluid (SRF) were determined for the AMD and RVO cases. Results: The level of VEGF165b was higher than the lower limit of detection (15 pg/ml) in 57% of the AMD cases (median, 16.4; range, <15-98 pg/ml) and 63% of the controls (median, 20.6; range, <15-46 pg/ml). The percentage of eyes with >15 pg/ml of VEGF165b was significantly lower in eyes with RVO (32%, p = 0.038). The VEGF165b level was not significantly different among the AMD subtypes, and it was not significantly correlated with the GLD, CFT, and SRF. In the RVO cases, the CFT and SRF thickness were greater in eyes with a VEGF level <15 pg/ml (p = 0.006, 0.048 respectively). Conclusions: The anti-angiogenic VEGF165b was low in eyes with RVO. Therapy based on balancing the pro- and anti-angiogenic factors might be a new approach to treat ocular vascular disorders.
    Current eye research 02/2014; · 1.51 Impact Factor
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    ABSTRACT: To compare the effect of posterior sub-Tenon's capsule triamcinolone acetonide (STTA) injection to that of pars plana vitrectomy (PPV) for diabetic macular edema (DME). The medical records of 50 patients (52 eyes) with DME were reviewed. Twenty-six eyes underwent STTA (20 mg) and the other 26 eyes underwent vitrectomy combined with cataract surgery. The central macular thickness (CMT), measured by optical coherence tomography, and best-corrected visual acuity (BCVA) were determined before and 1, 3, and 6 months after treatment. The differences in the BCVA and the CMT between the STTA group and the PPV group were not significant before or at any time after the treatment. In both the STTA and PPV groups, there were significant differences between the pre-treatment CMT and BCVA at any time after treatment. We recommend STTA injection for the treatment of DME.
    Clinical ophthalmology (Auckland, N.Z.) 01/2014; 8:825-30.
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    ABSTRACT: To compare the 1-year results of intravitreal ranibizumab combined with reduced-fluence photodynamic therapy (RF-PDT) to intravitreal ranibizumab (IVR) alone for eyes with polypoidal choroidal vasculopathy (PCV). We reviewed the medical records from 47 consecutive patients with PCV (47 naïve eyes). Seventeen eyes from 17 patients had one IVR treatment combined with RF-PDT followed by two additional IVR treatments (combined group), and 30 eyes from 30 patients were treated with 3 monthly IVR treatments (IVR group). All eyes had a follow-up period of at least 12 months. At 12 months, the mean logarithm of the minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) significantly improved from 0.55 to 0.38 logMAR units in the combined group (P=0.041) but did not change significantly in the IVR group (P=0.371). The central foveal thickness (CFT) was significantly thinner in both groups at 6 months (P<0.01). Additional IVR injections were required less frequently in the combined group (n=3; 17%) than in the IVR group (n=16; 53%) during the 12 month follow-up (P=0.029). The IVR and RF-PDT combination led to significant BCVA improvements and required fewer additional IVR treatments for at least 12 months in eyes with PCV.
    Clinical ophthalmology (Auckland, N.Z.) 01/2014; 8:235-41.
  • Toshiyuki Oshitari, Guzel Bikbova, Shuichi Yamamoto
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    ABSTRACT: The aim of this study is to examine whether the increased expression of phosphorylated c-Jun (p-c-Jun) and phosphorylated c-Jun N-terminal kinase (p-JNK) are significantly associated with neuronal cell death in diabetic rat retinas and retinas exposed to high glucose. Retinas isolated from six adult male Sprague-Dawley rats and six streptozotocin-induced diabetic rats (DM) were cultured in serum-free medium. The explants from non-diabetic controls were cultured in normal-glucose (N) or high-glucose (HG) medium. Furthermore, neurotrophin-4 (NT-4) and Taurine-conjugated ursodeoxycholic acid (TUDCA) were incubated in HG medium. After 7 days, the numbers of regenerating neurites were counted per explant. After counting, the explants were fixed, cryosectioned, and stained by TUNEL, and also immunostained for p-c-Jun and p-JNK. The numbers of TUNEL-positive, p-c-Jun- and p-JNK-immunopositive cells in the GCL were significantly higher and the numbers of regenerating neurites were significantly lower in the HG and the DM groups than in the N groups. In the HG groups supplemented with NT-4 and TUDCA, the numbers of TUNEL-positive, p-c-Jun- and p-JNK-immunopositive cells were significantly lower and the numbers of neurites were significantly higher than in the HG group without NT-4 and TUDCA. Increased expression of p-c-Jun and p-JNK are associated with neuronal cell death in diabetic rat retinas and retinas exposed to high glucose. Neuroprotective effect of TUDCA and NT-4 is correlated with the suppression of p-c-Jun and p-JNK expression. These results provide a better understanding of the neurodegenerative process underlying DR.
    Brain research bulletin 12/2013; · 2.18 Impact Factor
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    ABSTRACT: To compare the surgical outcomes during pars plana vitrectomy (PPV) for diffuse diabetic macular edema (DME) with pretreatment to those without pretreatment. The medical charts of 43 eyes of 46 patients who underwent PPV for DME were reviewed. The previously treated (Prev. Tx) group included 19 eyes of 20 patients who were pretreated with intravitreal bevacizumab, sub-Tenon injection of triamcinolone acetonide, and/or subthreshold micropulse diode laser photocoagulation before the PPV. The treatment naïve (Tx.Naïve) group included 24 eyes of 26 patients who underwent PPV alone. The central macular thickness (CMT) and best-corrected visual acuity (BCVA) were measured before treatment and 1, 3, and 6 months after. In both groups, BCVA at 3 and 6 months and CMT at 1 month or later were significantly better than preoperative visual acuity. CMT at 1 month or later significantly decreased from the preoperative value (p<0.05). The differences in the BCVA and CMT between the Prev. Tx and Tx.Naïve group were not significant. PPV either with or without preoperative treatments can significantly improve the BCVA and reduce the CMT in patients with diffuse DME.
    Nippon Ganka Gakkai zasshi 10/2013; 117(10):785-92.
  • Toshiyuki Oshitari, Shuichi Yamamoto, Sayon Roy
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    ABSTRACT: Abstract Purpose: To examine whether c-Fos, phosphorylated c-Jun (p-c-Jun), members of transcriptional factor activator protein 1 (AP-1) family and phosphorylated c-Jun N-terminal kinase (p-JNK) are associated with neuronal degeneration in retinas of diabetic patients. Materials and Methods: Retinal cryosections from five pairs of normal and five pairs of diabetic human eyes were immunostained for c-Fos, p-c-Jun and p-JNK followed by costaining with Fluoro-Jade B (FJB), a marker for identifying degenerative neurons. Additionally, cells were stained with 4, 6-diamidino-2-phenyl indole (DAPI) to facilitate counting the total number of cells. The number of c-Fos, p-c-Jun and p-JNK positive cells costained with FJB was assessed in the ganglion cell layer (GCL) together with the total number of DAPI-positive cells. Results: The number of FJB-positive cells in the GCL of diabetic retinas was significantly increased compared to those of non-diabetic retinas. The GCL of diabetic retinas, compared to those of the non-diabetic retinas, showed increased number of c-Fos, p-c-Jun and p-JNK-positive cells that coexisted with FJB-positive signals. Conclusions: This study indicates that increased expression of c-Fos, p-c-Jun, members of AP-1 transcriptional factor and p-JNK is associated with neuronal degeneration in the GCL of retinas in diabetic patients.
    Current eye research 09/2013; · 1.51 Impact Factor
  • Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
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    ABSTRACT: The purpose of this study was to determine the effect of low concentrations of advanced glycation end-products on neurite regeneration in isolated rat retinas, and to determine the effects of neurotrophin-4 on regeneration in advanced glycation end-products exposed retinas. Retinal explants of 4 adult Sprague-Dawley rats were cultured on collagen gel and were incubated in; 1) serum-free control culture media, 2) glucose-advanced glycation end-products-bovine serum albumin media, 3) glycolaldehyde-advanced glycation end-products-bovine serum albumin media, 4) glyceraldehyde-advanced glycation end-products-bovine serum albumin media, 5) glucose-advanced glycation end-products+neurotrophin-4 media, 6) glycolaldehyde-advanced glycation end-products+neurotrophin-4 media, or 7) glyceraldehyde-advanced glycation end-products+neurotrophin-4 supplemented culture media. After 7 days, the number of regenerating neurites from the explants was counted. Then, explants were fixed, cryosectioned, and stained for TUNEL. The ratio of TUNEL-positive cells to all cells in the ganglion cell layer was determined. Immunohistochemical examinations for the active-form of caspase-9 and apoptosis-inducing factor were performed. In retinas incubated with advanced glycation end-products containing media, the number of regenerating neurites were fewer than in retinas without advanced glycation end-products, and the number of TUNEL-positive cells and caspase-9- and apoptosis-inducing factor-immunopositive cells was significantly higher than in control media. Neurotrophin-4 supplementation increased the numbers of regenerating neuritis, and the number of TUNEL-positives, caspase-9-, and apoptosis-inducing factor-immunopositive cells were significantly fewer than that in advanced glycation end-products without neurotrophin-4 media. Low doses of advanced glycation end-products impede neurite regeneration in the rat retinas. Neurotrophin-4 significantly enhances neurite regeneration in retinas exposed to advanced glycation end-products.
    Brain research 08/2013; · 2.46 Impact Factor
  • T OSHITARI, S NONOMURA, M ARAI, S YAMAMOTO
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    ABSTRACT: Purpose To investigate the association of the Fourier domain optical coherence tomography (FD-OCT, Optovue) parameters with the level of HbA1c and duration of the diabetes mellitus (DM) in patients at the early stage of diabetic retinopathy (DR). Methods Thirty eyes of 30 patients with minimal DR (non-DR or mild NPDR) that were examined at the Chiba University Hospital from December 2011 to March 2012 were studied. The participants had no other ocular diseases and no history of surgeries. Three parameters embedded in the Optovue, the macular mapping 5 (MM5), RNFL, and ganglion cell complex (GCC), were performed, and the coefficients of correlation between these parameters and the HbA1c and the DM duration were analyzed with the Spearman rank correlation. A P
    Acta ophthalmologica 08/2013; 91(s252). · 2.44 Impact Factor
  • Guzel Bikbova, Toshiyuki Oshitari, Shuichi Yamamoto
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    ABSTRACT: Purpose: To determine whether the neuroprotective and regenerative effects of neurotrophin-4 (NT-4) is correlated with a reduction of caspase-9 and AIF expression in rat retinas exposed to AGEs. Methods: All of the procedures were performed in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Retinal explants of 4 adult SD rats were three- dimensionally cultured on collagen gels and incubated in; serum free control culture media, 10 μg/ml glucose-AGE-BSA media, 10 μg/ml glycolaldehyde-AGE-BSA media, 10 μg/ml glyceraldehyde-AGE- BSA media, glucose-AGE+100 ng/ml NT-4 media, glycol-AGE+100 ng/ml NT-4 media, or glycer-AGE+100 ng/ml NT-4 culture media. After 7 days, the number of regenerating neurites from the explants was counted under a phase-contrast microscope. After counting, the retinal explants were fixed, cryosectioned, and stained by TUNEL and DAPI. The ratio of TUNEL-positive cells to the number of DAPI-staining nuclei in the ganglion cell layer was calculated. Immunohistochemistry for the active form of caspase-9 and apoptosis-inducing factor (AIF) was performed. Statistical analyses were performed by one-way ANOVA. Results: In retinas incubated with AGEs (glucose-AGE, glycol-AGE, and glycer-AGE), the number of regenerating neurites was fewer than in retinas without AGE (P=0.0033, P=0.0044, P=0.0238). The number of TUNEL-positive cells (P<0.0001, P<0.0001, P<0.0001) and caspase-9-positive cells (P<0.0001; P<0.0001; P<0.0001) and AIF-positive cells (P=0.0004, P=0.0002, P=0.056) in the ganglion cell layer was higher than in controls. NT-4 supplementation increased, the number of regenerating neurites (P<0.0001, P<0.0001, P<0.0001). The number of TUNEL-positives cells (P<0.001, P=0.005, P=0.0003), caspase-9-positive cells (P<0.0001, P<0.0001, P<0.0001), and AIF-positive cells (P=0.026, P=0.026, P=0.016) was significantly fewer than in glucose-AGE without NT-4 and in glycol- AGE without NT-4 and in glycer-AGE without NT-4. Conclusions: Both caspase-dependent and caspase-independent cell death pathways are associated with retinal neuronal cell death in low dose AGE-BSA exposed rat retinas. Neuroprotective and regenerative effect of NT-4 is correlated with a reduction of caspase- 9 and AIF activation.
    ARVO 2013; 05/2013
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    ABSTRACT: The purpose of this study is to describe the 26-year-old patient with developed macular hole after bilateral laser in situ keratomileusis (LASIK). A macular hole with sharp margins and irregular surface of surrounding retina appeared in the left eye of the female 26-year-old patient two months after LASIK for correction of myopia (followup of 6 months). Although the best corrected visual acuity (BCVA) after LASIK was 1.0, after the macular hole has developed BCVA became 0.5. After surgery, the final visual acuity recovered to 0.7. Macular hole may develop after LASIK for myopia correction due to unknown changes of vitreoretinal interface. Complete informed consent must be obtained from patients with high myopic eyes before LASIK.
    Case reports in ophthalmological medicine. 01/2013; 2013:739474.
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    ABSTRACT: An 87-year-old Japanese man presented with retinal angiomatous proliferation (RAP) and a retinal pigment epithelium (RPE) detachment in his right eye. His decimal best-corrected visual acuity was 0.15 in the right eye, and optical coherence tomography (OCT) showed a vitreomacular adhesion in the right eye as well. After 3 monthly intravitreal injections of ranibizumab, the size and height of the RPE detachment was significantly reduced. The accumulated intra- and subretinal fluid also disappeared, but the vitreomacular traction remained. Pars plana vitrectomy was performed, and the posterior hyaloid was separated from the retina with a vitrectomy cutter without any intraoperative complications. Two months after the surgery, a large RPE tear was observed over the macular area. His visual acuity decreased to 0.06 and remained unchanged thereafter. We suggest that the small tear led to the larger RPE tear because vitreomacular traction was transmitted to the RPE through the fibrovascular tissue of the RAP during the creation of the hyaloid detachment. Because such an RPE tear has not been reported after vitrectomy for vitreomacular traction, surgeons need to pay special attention to this potential complication in eyes with vitreomacular traction and RAP.
    Case reports in ophthalmology. 01/2013; 4(3):165-171.
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    ABSTRACT: We present our findings in a case of primary neuroendocrine carcinoma (NEC) of the lacrimal gland and a case of primary Merkel cell carcinoma (MCC) of the eyelid. An 86-year-old man noticed a swelling of the left upper eyelid three months earlier. We performed excision biopsy and histopathological examination indicated that he had a primary NEC of the left lacrimal gland. He underwent chemotherapy followed by excision including the clinically visible margins and 50 Gy radiotherapy of the surgical margins. He had neither recurrence nor metastasis for 6 months since the last radiotherapy. An 80-year-old man noticed a nodule in the right upper eyelid and was referred to our hospital because the size was increasing rapidly. A complete surgical excision of the margins of the tumor was performed with histopathological confirmation of negative margins. The final diagnosis was a primary MCC of the right upper eyelid. After surgery, he underwent 50 Gy radiotherapy on the neck to prevent metastasis. No recurrence or metastasis was found for two years. Although primary NEC of the ocular adnexa is extremely rare, the tumor has high malignancy and readily metastasizes. Thus, combined therapy including surgery, radiotherapy, and/or chemotherapy is needed for complete management of NEC.
    Case reports in ophthalmological medicine. 01/2013; 2013:281351.
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    Albrecht von Graæes Archiv für Ophthalmologie 12/2012; · 1.93 Impact Factor

Publication Stats

490 Citations
92.17 Total Impact Points

Institutions

  • 2012
    • National Center for Global Health and Medicine in Japan
      Japan
  • 2001–2009
    • Chiba University
      • Department of Ophthalmology and Visual Science
      Chiba-shi, Chiba-ken, Japan
    • Chiba University Hospital
      Tiba, Chiba, Japan
  • 2005–2006
    • Boston University
      • Department of Medicine
      Boston, MA, United States