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安川 力ヤスカワ ツトム

所属部署医学研究科視覚科学分野
職名准教授
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Last Updated :2020/05/22

研究者基本情報

基本情報

    ORCID ID:0000-0001-9913-1905

学歴

  • 1996年04月 - 2000年03月, 京都大学大学院, 医学研究科
  • 1987年04月 - 1993年03月, 京都大学, 医学部
  • 1983年04月 - 1986年03月, 大阪府立天王寺高校

学位

  • 医学博士, 京都大学

所属学協会

  • 日本網膜硝子体学会
  • 日本眼薬理学会
  • 日本DDS学会
  • Association for Research in Vision and Ophthalmology
  • 日本眼科学会

委員歴

  •   2019年09月 - 現在, 日本眼薬理学会評議員
  •   2017年04月 - 現在, 日本眼科学会, 評議員
  •   2012年04月 - 現在, 理化学研究所, トランスレーショナルリサーチ倫理審査委員会委員

経歴

  •   2005年06月 - 現在, 名古屋市立大学

研究活動情報

研究分野

  • ライフサイエンス, 眼科学

研究キーワード

    加齢黄斑変性, ドラッグデリバリーシステム, 網膜, 眼科学

論文

  • Experimental proliferative vitreoretinopathy in rabbits by delivery of bioactive proteins with gelatin microspheres., Hirose F, Kiryu J, Tabata Y, Tamura H, Musashi K, Takase N, Usui H, Kuwayama S, Kato A, Yoshimura N, Ogura Y, Yasukawa T, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 129, 267 - 272,   2018年08月, 査読有り
  • In vitro drusen model - three-dimensional spheroid culture of retinal pigment epithelial cells., Usui H, Nishiwaki A, Landiev L, Kacza J, Eichler W, Wako R, Kato A, Takase N, Kuwayama S, Ohashi K, Yafai Y, Bringmann A, Kubota A, Ogura Y, Seeger J, Wiedemann P, Yasukawa T, Journal of cell science, 132, (4) ,   2018年08月, 査読有り
  • Flattening of retinal pigment epithelial detachments after pneumatic displacement of submacular hemorrhages secondary to age-related macular degeneration., Kimura M, Yasukawa T, Shibata Y, Kato A, Hirano Y, Uemura A, Yoshida M, Ogura Y, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie,   2018年07月, 査読有り
  • Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration., Akiyama M, Takahashi A, Momozawa Y, Arakawa S, Miya F, Tsunoda T, Ashikawa K, Oshima Y, Yasuda M, Yoshida S, Enaida H, Tan X, Yanagi Y, Yasukawa T, Ogura Y, Nagai Y, Takahashi K, Fujisawa K, Inoue M, Arakawa A, Tanaka K, Yuzawa M, Kadonosono K, Sonoda KH, Ishibashi T, Kubo M, Journal of human genetics,   2018年07月, 査読有り
  • A simple lens-sparing technique to treat hypotonic maculopathy secondary to large cyclodialysis., Kimura M, Yasukawa T, Ogura Y, American journal of ophthalmology case reports, 10, 300 - 303,   2018年06月, 査読有り
  • Peripheral Microvascular Abnormalities Detected by Wide-Field Fluorescein Angiography in Eyes with Branch Retinal Vein Occlusion., Yasuda Y, Hirano Y, Esaki Y, Tomiyasu T, Suzuki N, Yasukawa T, Yoshida M, Ogura Y, Ophthalmic research, 1 - 8,   2018年05月, 査読有り
  • Best surgical technique and outcomes for large macular holes: retrospective multicentre study in Japan., Yamashita T, Sakamoto T, Terasaki H, Iwasaki M, Ogushi Y, Okamoto F, Takeuchi M, Yasukawa T, Takamura Y, Ogata N, Nakamura Y, writing committee of Japan-Clinical Retina, Research Team, J-CREST, Acta ophthalmologica,   2018年04月, 査読有り
  • Tissue Plasminogen Activator as an Antiangiogenic Agent in Experimental Corneal Neovascularization in Rabbits., Arai KI, Yasukawa T, Kato A, Kubota A, Usui H, Takase N, Kuwayama S, Ogura Y, Ophthalmic research, 59, (3) 170 - 175,   2018年, 査読有り
  • Six-month results of intravitreal ranibizumab for macular edema after branch retinal vein occlusion in a single-center prospective study: visual outcomes and microaneurysm formation., Kawamura M, Hirano Y, Yoshida M, Mizutani T, Sugitani K, Yasukawa T, Ogura Y, Clinical ophthalmology (Auckland, N.Z.), 12, 1487 - 1494,   2018年, 査読有り
  • Wide-field fluorescein and indocyanine green angiography findings in the eyes with Vogt-Koyanagi-Harada disease., Kurobe R, Hirano Y, Niwa N, Sugitani K, Yasukawa T, Yoshida M, Ogura Y, Journal of ophthalmic inflammation and infection, 7, (1) ,   2017年12月, 査読有り
  • A Multicenter Randomized Controlled Study of Antioxidant Supplementation with Lutein for Chronic Central Serous Chorioretinopathy, Ari Shinojima, Miki Sawa, Tetsuju Sekiryu, Yuji Oshima, Ryusaburo Mori, Chikako Hara, Yukinori Sugano, Aki Kato, Hitomi Asato, Mitsuko Yuzawa, Fumi Gomi, Yuichiro Ogura, Tatsuro Ishibashi, Tomoaki Nanri, Tsutomu Yasukawa, OPHTHALMOLOGICA, 237, (3) 159 - 166,   2017年, 査読有り, Purpose: To investigate functional and morphological changes in patients with chronic central serous chorioretinopathy after supplementation with antioxidants containing lutein or a placebo. Procedures: One hundred eyes of 100 patients were randomly divided into 2 groups, one taking tablets with lutein plus other antioxidants and the other taking a placebo for 6 months. Best-corrected visual acuity (BCVA) and the subfoveal fluid height on optical coherence tomography were measured. Results: Seventy-nine patients (37 in the supplementation and 42 in the placebo group) completed the 6-month follow-up. In the supplementation group, mean BCVA showed significant improvement (p = 0.003), while there was no significant change in the placebo group (p = 0.589). The mean subfoveal fluid height was significantly reduced, by 28.6%, in the supplementation group (p = 0.028), in contrast to 3.3% in the placebo group (p = 0.898). Conclusions: Antioxidant supplementation significantly reduced subfoveal fluid height. The impacts of antioxidant supplementation on BCVA remain to be elucidated in future studies. (C) 2017 S. Karger AG, Basel
  • Low-frequency coding variants in CETP and CFB are associated with susceptibility of exudative age-related macular degeneration in the Japanese population, Yukihide Momozawa, Masato Akiyama, Yoichiro Kamatani, Satoshi Arakawa, Miho Yasuda, Shigeo Yoshida, Yuji Oshima, Ryusaburo Mori, Koji Tanaka, Keisuke Mori, Satoshi Inoue, Hiroko Terasaki, Tetsuhiro Yasuma, Shigeru Honda, Akiko Miki, Maiko Inoue, Kimihiko Fujisawa, Kanji Takahashi, Tsutomu Yasukawa, Yasuo Yanagi, Kazuaki Kadonosono, Koh-Hei Sonoda, Tatsuro Ishibashi, Atsushi Takahashi, Michiaki Kubo, HUMAN MOLECULAR GENETICS, 25, (22) 5027 - 5034,   2016年11月, 査読有り, Age-related macular degeneration (AMD) is a major cause of blindness in the elderly. Previous sequencing studies of AMD susceptibility genes have revealed the association of rare coding variants in CFH, CFI, C3 and C9 in European population; however, the impact of rare or low-frequency coding variants on AMD susceptibility in other populations is largely unknown. To identify the role of low-frequency coding variants on exudative AMD susceptibility in a Japanese population, we analysed the association of coding variants of 34 AMD candidate genes in the two-stage design by a multiplex PCR-based target sequencing method. We used a total of 2,886 (1st: 827, 2nd: 2,059) exudative AMD cases including typical AMD, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation and 9,337 (1st: 3,247 2nd: 6,090) controls. Gene-based analysis found a significant association of low-frequency variants (minor allele frequency (MAF)<0.05) in CETP, C2 and CFB. The association of CETP remained after conditioned with all known genome-wide association study (GWAS) associated variants. In addition, when we included only disruptive variants, enrichment of rare variants (MAF<0.01) was also observed after conditioned with all GWAS associated variants (P = 1.03 x 10(-6), odds ratio (OR) = 2.48). Haplotype and conditional analysis of the C2-CFB-SKIV2L locus showed a low-frequency variant (R74H) in CFB would be individually associated with AMD susceptibility independent of the GWAS associated SNP. These findings highlight the importance of target sequencing to reveal the impact of rare or low-frequency coding variants on disease susceptibility in different ethnic populations.
  • Tissue Plasminogen Activator as an Antiangiogenic Agent in Experimental Laser-Induced Choroidal Neovascularization in Mice, Daisuke Ozone, Takeshi Mizutani, Miho Nozaki, Masaharu Ohbayashi, Norio Hasegawa, Aki Kato, Tsutomu Yasukawa, Yuichiro Ogura, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57, (13) 5348 - 5354,   2016年10月, 査読有り, PURPOSE. We investigate the antiangiogenic efficacy of tissue plasminogen activator (tPA) on experimental laser-induced choroidal neovascularization (CNV) in mice. METHODS. After CNV was induced by laser photocoagulation in 92 C57BL/6J wild-type mice, tPA (4 or 40 international units [IU]/mu l) or PBS was injected intravitreally immediately after laser injury. Fluorescein angiography was performed on day 7 to grade CNV leakage. The CNV volume was measured by confocal microscopy in eyes enucleated 7 days after laser injury. Immunohistochemical studies were performed 3 days after laser injury to evaluate fibrin/fibrinogen and CD31 expression. The possible adverse effects of tPA were assessed by electroretinography (ERG) and histology on day 7. RESULTS. Intravitreal administration of tPA significantly suppressed CNV leakage and CNV volume in a dose-dependent manner (P < 0.01). Intravitreal injection of tPA suppressed fibrin/fibrinogen and CD31 expression in laser-induced lesions. Histologic examination and ERG showed no evidence of retinal toxicity in eyes injected with tPA. CONCLUSIONS. Intravitreal injection of tPA suppressed fibrin/fibrinogen expression and laser-induced CNV. The current results suggested that tPA may be a potential therapeutic adjuvant for treating CNV.
  • Retinal Hemodynamics Seen on Optical Coherence Tomography Angiography Before and After Treatment of Retinal Vein Occlusion, Norihiro Suzuki, Yoshio Hirano, Taneto Tomiyasu, Yuya Esaki, Akiyoshi Uemura, Tsutomu Yasukawa, Munenori Yoshida, Yuichiro Ogura, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57, (13) 5681 - 5687,   2016年10月, 査読有り, PURPOSE. This study evaluates the retinal hemodynamics using optical coherence tomography angiography (OCTA) before and after anti-vascular endothelial growth factor (VEGF) therapy in patients with macular edema associated with retinal vein occlusion (RVO). METHODS. Twelve patients (23 eyes; mean age, 64 years) were included (eight eyes with branch RVO, four with central RVO, and 11 unaffected fellow eyes. The best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were measured before and 6 months after treatment. The foveal avascular zone (FAZ), nonperfused areas (NPAs), and flow area were evaluated with OCTA before and after treatment. RESULTS. The BCVA and CRT improved significantly after treatment. In eyes with RVO, the baseline FAZ in the retinal deep capillary layer was larger than in fellow eyes and enlarged in the retinal superficial and deep capillary layers after therapy; NPAs decreased after therapy, especially in the retinal deep capillary layer; and the baseline flow area was smaller than in fellow eyes and improved after therapy, especially in the retinal deep capillary layer. CONCLUSIONS. Optical coherence tomography angiography can evaluate the retinal hemodynamics in patients with RVOs. Anti-VEGF therapy reduced the NPA size and improved retinal blood flow, especially in the retinal deep layer. The current results suggested that anti-VEGF therapy might improve retinal deep ischemia in patients with RVO in the retinal deep layer, which is abundant in capillaries.
  • Microaneurysms cause refractory macular edema in branch retinal vein occlusion, Taneto Tomiyasu, Yoshio Hirano, Munenori Yoshida, Norihiro Suzuki, Takeshi Nishiyama, Akiyoshi Uemura, Tsutomu Yasukawa, Yuichiro Ogura, SCIENTIFIC REPORTS, 6,   2016年07月, 査読有り, Intravitreal anti-vascular endothelial growth factor (VEGF) agents can treat macular edema (ME) in branch retinal vein occlusion (BRVO). However, refractory ME, the mechanism of which is not well elucidated, occurs frequently. Sixty-six eyes with ME secondary to BRVO were enrolled in this retrospective observational case-control study. Twenty eyes received a sub-Tenon's capsule injection of triamcinolone acetonide (STTA), 22 eyes an intravitreal anti-VEGF injection (ranibizumab), 16 eyes were switched from STTA to ranibizumab, 4 eyes underwent vitrectomy, and 4 eyes were untreated. Multiple regression analysis and multivariate logistic regression analysis were conducted, respectively, to identify independent predictors of visual acuity (VA) prognosis and risk factors for refractory ME longer than 1 year. The mechanism of refractory ME and therapeutic approaches for identified risk factors also were investigated. Thirty-four (52%) eyes had refractory ME for over 1 year. Microaneurysms were identified as risk factors for refractory ME, leading to poor final VA. Ranibizumab suppressed microaneurysm formation and refractory ME, with early administration more effective. For already formed microaneurysms, laser photocoagulation reduced additional treatments. Microaneurysms may cause refractory ME in BRVO. Alternative therapy to suppress microaneurysms should be considered to prevent refractory ME in patients with BRVO.
  • Densitometry of Choroidal Vessels in Eyes With and Without Central Serous Chorioretinopathy by Wide-Field Indocyanine Green Angiography, Shuichiro Hirahara, Tsutomu Yasukawa, Aoi Kominami, Miho Nozaki, Yuichiro Ogura, AMERICAN JOURNAL OF OPHTHALMOLOGY, 166, 103 - 111,   2016年06月, 査読有り, PURPOSE: To develop a new method to quantify the choroidal vessel density by binarizing ultra-wide-field indocyanine green angiography (ICGA) images and determine whether values are altered in diseased eyes. DESIGN: Reliability and validity analysis. METHODS: Ultra-wide-field fluorescein angiography (FA) and ICGA images were obtained using an ultra wide-field imaging device (Optos California ultra-wide field imaging device; Dunfermline, Scotland, UK) in 11 eyes of 11 patients without chorioretinal diseases. The angiographic signals of the choroidal vessels were determined by subtracting those of the retinal vasculature and optic disc on the FA images from the ICGA images, binarized by Niblack's method, and the choroidal vessel " density calculated. Reproducibility of the method was assessed by calculating the coefficient of variance, coefficient of repeatability, and intraclass correlation coefficient.. The relationships between age, spherical equivalent refractive error (SERE), and intraocular pressure and the vasculature density were assessed. To investigate possible impacts of chorioretinal diseases on the vasculature density, 10 eyes of 7 patients with central serous chorioretinopathy (CSC) were compared with the 11 control eyes. RESULTS: Choroidal vessels were contrasted by binarizing ICGA images. The method to quantify the choroidal vessel density showed high reproducibility. The SERE was correlated significantly (r = 0.573, P < .05) with the vasculature density. In the 11 control eyes, the vasculature density was 34.26% +/- 0.77% in the entire area, 31.37% +/- 0.97% in the superior portion, 36.98% +/- 0.88% in the inferior portion, 37.01% +/- 1.44% in the posterior portion, and 34.17% +/- 0.77% in the peripheral portion. In eyes with CSC, the density was significantly (P < .05) higher: 36.46% +/- 0.49%, 34.02% +/- 0.97%, 38.65% +/- 0.27%, 41.04% +/- 0.82%, and 36.36% +/- 0.51%, respectively. CONCLUSIONS: Binarization of ultra-wide-field ICGA images enabled quantification of the choroidal vessel density, which was altered in eyes with CSC. This method of measuring the choroidal vessel density may provide new insights into diagnosing and treating chorioretinal diseases. (C) 2016 Elsevier Inc. All rights reserved.
  • Combination therapy with intravitreal tissue plasminogen activator and ranibizumab for subfoveal type 2 choroidal neovascularization, Ikuko Kachi, Tsutomu Yasukawa, Aki Kato, Noriaki Takase, Hiroshi Morita, Ayae Kubota, Yoshio Hirano, Akiyoshi Uemura, Yuichiro Ogura, JAPANESE JOURNAL OF OPHTHALMOLOGY, 60, (3) 179 - 186,   2016年05月, 査読有り, Purpose Fibrovascular scar formation related to subfoveal type 2 choroidal neovascularization (CNV) often causes severe vision loss in eyes with age-related macular degeneration. The authors assessed additional impacts of intravitreal tissue plasminogen activator (tPA), a fibrinolytic compound, combined with intravitreal ranibizumab (IVR) on subfoveal type 2 CNV. Methods Eight eyes of eight patients with type 2 CNV underwent intravitreal injections of ranibizumab and tPA (IVR/tPA) (40 kIU). Twelve eyes of 12 patients with type 2 CNV were treated with only IVR injections, as the control group. For retreatment, IVR was performed as needed. The best-corrected visual acuity (BCVA) and the central retinal thickness (CRT) and macular volume (MV) on optical coherence tomography were recorded periodically for 6 months. Results The subretinal fibrinous and fibrovascular tissue complex regressed or contracted immediately after administration of IVR/tPA in contrast to IVR monotherapy. The total numbers of IVR injections did not differ significantly between the two groups. The mean logarithm of the minimum angle of resolution BCVA in the combination therapy group improved significantly from 0.72 at baseline to 0.51 at month 6 and was superior to that in the monotherapy group (0.70-0.79). The improvements of the mean CRT and MV in the combination therapy group were superior to the monotherapy group. No tPA-related complications developed. Conclusions tPA may have a specific ability to regress already formed subretinal fibrinous and fibrovascular tissue complexes in eyes with type 2 CNV, potentially increasing the chances of visual improvement through a synergistic relationship with anti-VEGF therapies.
  • Malondialdehyde induces autophagy dysfunction and VEGF secretion in the retinal pigment epithelium in age-related macular degeneration, Fuxiang Ye, Hiroki Kaneko, Yumi Hayashi, Kei Takayama, Shiang-Jyi Hwang, Yuji Nishizawa, Reona Kimoto, Yosuke Nagasaka, Taichi Tsunekawa, Toshiyuki Matsuura, Tsutomu Yasukawa, Takaaki Kondo, Hiroko Terasaki, FREE RADICAL BIOLOGY AND MEDICINE, 94, 121 - 134,   2016年05月, 査読有り, Age-related macular degeneration (AMD) is a major cause of blindness in developed countries and is closely related to oxidative stress, which leads to lipid peroxidation. Malondialdehyde (MDA) is a major byproduct of polyunsaturated fatty acid (PUFA) peroxidation. Increased levels of MDA have been reported in eyes of AMD patients. However, little is known about the direct relationship between MDA and AMD. Here we show the biological importance of MDA in AMD pathogenesis. We first confirmed that MDA levels were significantly increased in eyes of AMD patients. In ARPE-19 cells, a human retinal pigment epithelial cell line, MDA treatment induced vascular endothelial growth factor (VEGF) expression alternation, cell junction disruption, and autophagy dysfunction that was also observed in eyes of AMD patients. The MDA-induced VEGF increase was inhibited by autophagy-lysosomal inhibitors. Intravitreal MDA injection in mice increased laser-induced choroidal neovascularization (laser-CNV) volumes. In a mouse model fed a high-linoleic acid diet for 3 months, we found a significant increase in MDA levels, autophagic activity, and laser-CNV volumes. Our study revealed an important role of MDA, which acts not only as a marker but also as a causative factor of AMD pathogenesis-related autophagy dysfunction. Furthermore, higher dietary intake of linoleic acid promoted CNV progression in mice with increased MDA levels. (C) 2016 Elsevier Inc. All rights reserved.
  • Microvascular Abnormalities on Optical Coherence Tomography Angiography in Macular Edema Associated With Branch Retinal Vein Occlusion, Norihiro Suzuki, Yoshio Hirano, Munenori Yoshida, Taneto Tomiyasu, Akiyoshi Uemura, Tsutomu Yasukawa, Yuichiro Ogura, AMERICAN JOURNAL OF OPHTHALMOLOGY, 161, 126 - 132,   2016年01月, 査読有り, PURPOSE: To determine the ability of optical coherence tomography (OCT) angiography to image the microvascular structures compared with fluorescein angiography (FA) in patients with macular edema associated with branch retinal vein occlusion (BRVO). DESIGN: Retrospective, observational, consecutive case series. METHODS: Twenty-eight eyes of 27 patients (14 men, 13 women; mean age, 68.4 years) with macular edema associated with BRVO were enrolled. Simultaneous OCT angiography and FA were performed in all patients to evaluate the microvascular abnormalities and nonperfused areas. RESULTS: OCT angiography detected nonperfused areas in 28 eyes and FA in 18 eyes. The respective findings of superficial capillary telangiectasias by OCT angiography and FA were 13 and 11 eyes, for deep capillary telangiectasias 28 eyes and 11 eyes, for collateral vessels 18 eyes and 16 eyes, and for microaneurysms 13 eyes and 14 eyes. OCT angiography facilitated differential layer analysis of microaneurysms and collaterals as well as capillary telangiectasias in the retina. CONCLUSIONS: OCT angiography can visualize microvascular abnormalities equally well or better than FA in eyes with BRVO. Multimodal imaging using OCT angiography and FA can be a powerful tool to evaluate the pathology in BRVO. (C) 2016 by Elsevier Inc. All rights reserved.
  • Investigation of the Etiology of Central Serous Chorioretinopathy Using En-Face Optical Coherence Tomography and Indocyanine Green Angiography, Ari Shinojima, Kyoko Fujita, Ryusaburo Mori, Akiyuki Kawamura, Mitsuko Yuzawa, Tsutomu Yasukawa, OPHTHALMOLOGICA, 236, (2) 100 - 107,   2016年, 査読有り, Purpose: To identify locations of hypofluorescent lesions on late-phase indocyanine green angiography (ICGA) in patients with central serous chorioretinopathy (CSC) using en face optical coherence tomography (OCT). Procedures: We retrospectively studied 25 consecutive untreated CSC patients, using swept-source OCT and ICGA. En-face swept source OCT images were automatically segmented and flattened with Bruch's membrane (BrM). We compared the sizes of hyperreflective areas in the 25 CSC and 25 contralateral eyes on en-face images and hypofluorescent areas on ICGA after 30 min. Results: All 25 CSC eyes and 13 contralateral eyes showed abnormal hypofluorescent areas on late-phase ICGA and hyperreflective areas on en-face OCT from BrM to the choriocapillaris, and these findings correlated with the abnormal areas (r = 0.9988; p < 0.001). Conclusions: In CSC patients, we detected abnormal hypofluorescence on ICGA in the late phase, which corresponded to abnormal hyper reflective areas from BrM to the choriocapillaris level in en face images. (C) 2016 S. Karger AG, Basel
  • Preoperative optical coherence tomography visualization of epiretinal membranes enhances surgical strategies., Suzuki N, Hirano Y, Ichida M, Tomiyasu T, Esaki Y, Yasukawa T, Ogura Y, Clinical ophthalmology (Auckland, N.Z.), 10, 2297 - 2302,   2016年, 査読有り
  • Evaluation of peripheral fundus autofluorescence in eyes with wet age-related macular degeneration., Suetsugu T, Kato A, Yoshida M, Yasukawa T, Nishiwaki A, Hasegawa N, Usui H, Ogura Y, Clinical ophthalmology (Auckland, N.Z.), 10, 2497 - 2503,   2016年, 査読有り
  • Prevention of increased abnormal fundus autofluorescence with blue light-filtering intraocular lenses., Nagai H, Hirano Y, Yasukawa T, Morita H, Nozaki M, Wolf-Schnurrbusch U, Wolf S, Ogura Y, Journal of cataract and refractive surgery, 41, (9) 1855 - 1859,   2015年09月, 査読有り
  • Resolution of exudative changes refractory to ranibizumab after aflibercept injections at the margin of inferior staphyloma in tilted disc syndrome., Hirano Y, Yasukawa T, Tsukada A, Yokoyama S, Ito Y, Nakazawa Y, Ophthalmic surgery, lasers & imaging retina, 46, (3) 384 - 386,   2015年03月, 査読有り
  • Intravitreal ranibizumab for patients with neovascular age-related macular degeneration with good baseline visual acuity., Kato A, Yasukawa T, Suga K, Hirano Y, Nozaki M, Yoshida M, Ogura Y, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 233, (1) 27 - 34,   2015年, 査読有り
  • Vitrectomy without gas tamponade for macular retinoschisis associated with normal-tension glaucoma., Orazbekov L, Yasukawa T, Hirano Y, Ogura S, Usui H, Nozaki M, Ogura Y, Ophthalmic surgery, lasers & imaging retina, 46, (1) 107 - 110,   2015年01月, 査読有り
  • Surgical Videos with Synchronised Vertical 2-Split Screens Recording the Surgeons' Hand Movement., Kaneko H, Ra E, Kawano K, Yasukawa T, Takayama K, Iwase T, Terasaki H, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 234, (4) 243 - 246,   2015年, 査読有り
  • Indocyanine Green Angiography-Guided Focal Laser Photocoagulation for Diabetic Macular Edema., Ogura S, Yasukawa T, Kato A, Kuwayama S, Hamada S, Hirano Y, Uemura A, Yoshida M, Ogura Y, Ophthalmologica. Journal international d'ophtalmologie. International journal of ophthalmology. Zeitschrift fur Augenheilkunde, 234, (3) 139 - 150,   2015年, 査読有り
  • Wide-Field Fundus Autofluorescence Imaging to Evaluate Retinal Function in Patients With Retinitis Pigmentosa, Shuntaro Ogura, Tsutomu Yasukawa, Aki Kato, Hideaki Usui, Yoshio Hirano, Munenori Yoshida, Yuichiro Ogura, AMERICAN JOURNAL OF OPHTHALMOLOGY, 158, (5) 1093 - 1098,   2014年11月, 査読有り, PURPOSE: To study the correlation between the visual fields (VF) and wide-field fundus autofluorescence (FAF) in patients with retinitis pigmentosa (RP). DESIGN: Retrospective, observational, consecutive case series. METHODS: Twenty-four eyes of 12 patients diagnosed with RP were enrolled. The VFs measured by Goldmann perimetry and wide-field FAF images were compared for each eye. The relationship between the areas of hypoautofluorescence on the wide-field FAF images and scotoma on Goldmann perimetry were evaluated. The VF and FAF images in the central 60 degrees were trimmed and superimposed to calculate the percentage agreement between the hypoautofluorescence and the scotomas and between the isoautofluorescence and hyperautofluorescence and the remaining VFs. RESULTS: The areas of hypoautofluorescence on the FAF images were correlated significantly (R = 0.86, P < .001) with the areas of the VF defects on Goldmann perimetry. The mean percentage agreement between the hypoautofluorescence and the scotomas was 91.0% +/- 7.7% and that of the isoautofluorescence and hyperautofluorescence with the remaining VFs was 84.5% +/- 7.4%. The areas of geographic hypoautofluorescence with or without hyperautofluorescent bands reflected the VF defects, while nummular or mottled hypoautofluorescence without VF defects was seen in 7 eyes. CONCLUSIONS: These results suggested that wide-field FAF imaging is useful to evaluate the remaining retinal function in patients with RP. Abnormal fundus autofluorescence precedes loss of retinal function and is helpful for monitoring disease progression. (C) 2014 by Elsevier Inc. All rights reserved.
  • [Causes and prevalence of visual impairment in Japan]., Wako R, Yasukawa T, Kato A, Omori T, Ishida S, Ishibashi T, Ogura Y, Nippon Ganka Gakkai zasshi, 118, (6) 495 - 501,   2014年06月, 査読有り
  • Recovery of retinal pigment epithelium correlating with restoration of retinal sensitivity in eyes with a retinal pigment epithelial tear, Yoshio Hirano, Tsutomu Yasukawa, Takeshi Mizutani, Munenori Yoshida, Yuichiro Ogura, ACTA OPHTHALMOLOGICA, 92, (1) 94 - 97,   2014年02月, 査読有り
  • Inhibition of autophagy induces retinal pigment epithelial cell damage by the lipofuscin fluorophore A2E, Khandakar A. S. M. Saadat, Yusuke Murakami, Xue Tan, Yoko Nomura, Tsutomu Yasukawa, Eiichi Okada, Yasuhiro Ikeda, Yasuo Yanagi, FEBS OPEN BIO, 4, 1007 - 1014,   2014年, 査読有り, In this study, we show augmented autophagy in the retinal pigment epithelial cell line ARPE-19 when cultured in the presence of the lipofuscin pigment A2E. A2E alone does not induce RPE cell death, but cell death was induced in the presence of A2E with the autophagy inhibitor 3-methyladenine (3MA), with a concomitant increase in the generation of mitochondrial reactive oxygen species. On the other hand, the ATP production capacity of mitochondria was decreased in the presence of A2E, and pharmacological inhibition of autophagy had no additional effects. The altered mRNA expression level of mitochondrial function markers was confirmed by real-time polymerase chain reaction, which showed that the antioxidant enzymes SOD1 and SOD2 were not reduced in the presence of A2E alone, but significantly suppressed with the addition of 3MA. Furthermore, transmission electron micrography revealed autophagic vacuole formation in the presence of A2E, and inhibition of autophagy resulted in the accumulation of abnormal mitochondria with loss of cristae. Spheroid culture of human RPE cells demonstrated debris accumulation in the presence of A2E, and this accumulation was accelerated in the presence of 3MA. These results indicate that autophagy in RPE cells is a vital cytoprotective process that prevents the accumulation of damaged cellular molecules. (C) 2014 The Authors. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
  • Three-dimensional spheroidal culture visualization of membranogenesis of Bruch's membrane and basolateral functions of the retinal pigment epithelium., Sato R, Yasukawa T, Kacza J, Eichler W, Nishiwaki A, Iandiev I, Ohbayashi M, Kato A, Yafai Y, Bringmann A, Takase A, Ogura Y, Seeger J, Wiedemann P, Investigative ophthalmology & visual science, 54, (3) 1740 - 1749,   2013年03月, 査読有り
  • Possible implications of acid-sensing ion channels in ischemia-induced retinal injury in rats., Miyake T, Nishiwaki A, Yasukawa T, Ugawa S, Shimada S, Ogura Y, Japanese journal of ophthalmology, 57, (1) 120 - 125,   2013年01月, 査読有り
  • Comparative study of the effects of room air and sulfur hexafluoride gas tamponade on functional and morphological recovery after macular hole surgery: a retrospective study., Usui H, Yasukawa T, Hirano Y, Morita H, Yoshida M, Ogura Y, Ophthalmic research, 50, (4) 227 - 230,   2013年, 査読有り
  • Spatio-temporal understanding of the pathology of acute posterior multifocal placoid pigment epitheliopathy, Yoshio Hirano, Tsutomu Yasukawa, Hiroyuki Nagai, Yuichiro Ogura, JAPANESE JOURNAL OF OPHTHALMOLOGY, 56, (4) 371 - 374,   2012年07月, 査読有り, We report a case of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and the associated spatio-temporal pathologic findings of this disease. A 29-year-old woman with bilateral recurrent APMPPE. The patient complained of bilateral blurred vision. The best-corrected visual acuity was 20/13 bilaterally. Slit-lamp examination revealed bilateral, multiple, yellowish-white, flat, placoid lesions over the posterior fundus. A hyperreflective area between the outer nuclear layer (ONL), and the photoreceptor inner and outer segments (IS/OS) visible on the optical coherence tomographic images and a hyperfluorescent area identified on the late-phase fluorescein angiographic images were spatio-temporally consistent with the presence of the placoid lesions. The pattern of juxtafoveal hyperfluorescent spots was accompanied by multiple hypofluorescent, wedge-shaped lesions. The hypofluorescent lesions visible on the indocyanine green angiographic (ICGA) images were irregular in shape and intensity. APMPPE was diagnosed, and the patient was treated with an initial 30 mg dose of oral prednisolone, followed by a 3-week taper. The lesions recurred in an area where hypofluorescent lesions had not occurred previously, while the previous hypofluorescent spots resolved completely without the hyperfluorescence associated with vascular remodeling. These findings suggest that the placoid appearance of APMPPE may correspond to edema between the ONL and the photoreceptor IS/OS and that the hypofluorescent lesions characteristic of this condition visible on ICGA images might reflect infiltration and subsequent blockage of choroidal vasculature-derived fluorescence.
  • Anti-angiogenic effects of the receptor tyrosine kinase inhibitor, pazopanib, on choroidal neovascularization in rats, Yousef Yafai, Xiu Mei Yang, Marc Niemeyer, Akiko Nishiwaki, Johannes Lange, Peter Wiedemann, Andrew G. King, Tsutomu Yasukawa, Wolfram Eichler, EUROPEAN JOURNAL OF PHARMACOLOGY, 666, (1-3) 12 - 18,   2011年09月, 査読有り, Neovascularization in the eye is a major cause of irreversible vision loss. The present study was undertaken to determine mechanisms through which pazopanib, a drug that targets multiple receptor tyrosine kinases such as VEGF receptors, inhibits angiogenesis and experimental choroidal neovascularization (CNV). Pazopanib inhibited VEGF expression by retinal pigment epithelium (RPE) cells and choroidal endothelial cells (CEC), decreased VEGF-induced cellular migration in a dose-dependent manner and suppressed extracellular signal-regulated kinase (ERK)-1/-2 phosphorylation. To assess the impact of pazopanib in vivo, CNV was induced in rats by rupturing the Bruch's membrane by laser coagulation. These experiments demonstrated that twice-daily topical eye drop treatment significantly (P<0.001) decreased leakage from photocoagulated lesions by 89.5%. Furthermore, the thickness of the developed CNV lesions was significantly inhibited by 71.7% (P<0.001) in pazopanib-treated eyes, and immunoreactivity of VEGF was lower than in control eyes. Our data suggest that pazopanib is a promising inhibitor of angiogenesis leading to an effective inhibition of CNV development in vivo. This activity can be largely ascribed to the down-regulation of VEGF release in the retina as well as to impaired VEGF-induced signaling and chemotaxis. Using a convenient topical dosing regimen, pazopanib may prove useful for treating a variety of ocular neovascular diseases such as neovascular age-related macular degeneration. (C) 2011 Elsevier B.V. All rights reserved.
  • Pneumatic displacement of submacular hemorrhage with or without tissue plasminogen activator, Takeshi Mizutani, Tsutomu Yasukawa, Yuya Ito, Ayae Takase, Yoshio Hirano, Munenori Yoshida, Yuichiro Ogura, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 249, (8) 1153 - 1157,   2011年08月, 査読有り, To assess the efficacy and complications of intravitreal injection of sulfur hexafluoride (SF(6)) gas with/without tissue plasminogen activator (tPA) for displacing submacular hemorrhage. The medical records of 53 eyes that underwent pneumatic displacement for submacular hemorrhage were reviewed retrospectively. Submacular hemorrhage was related to exudative age-related macular degeneration (AMD) in 39 eyes and ruptured retinal arterial macroaneurysms in 14 eyes, and treated with intravitreal injection of SF(6) gas with or without tPA. Compared with preoperatively (mean follow-up, 18.4 months), the final visual acuity (VA) improved by 0.3 or more logMAR unit in 34 eyes (64.2%), stabilized within 0.3 logMAR in 15 eyes (28.3%), and deteriorated in four eyes (7.5%). In eyes with AMD, hemorrhage including vitreous hemorrhage recurred in eight (22.2%) of 36 eyes treated with tPA and one (33.3%) of three eyes not treated with tPA. In eyes with macroaneurysms, hemorrhage recurred in four (100%) of four eyes treated with tPA and in one (10.0%) of ten eyes without tPA (p < 0.005). Eight eyes underwent vitrectomy for recurrent hemorrhage. During follow-up, photodynamic therapy or intravitreal ranibizumab or pegaptanib was administered in 16 (41.0%) of 39 eyes with AMD. Postoperative ocular hypertension persisting over 3 days was not observed. Intravitreal SF(6) gas plus tPA may be well-accepted, with good visual outcomes and no remarkable complications for treating submacular hemorrhage secondary to AMD. tPA is not recommended for ruptured retinal arterial macroaneurysms, because of a higher incidence of subsequent vitreous hemorrhage. Pneumatic displacement of submacular hemorrhage without tPA may provide good visual outcomes with less re-bleeding.
  • [Long-term outcome of radiation therapy for exudative age-related macular degeneration in Japan]., Mizutani T, Yasukawa T, Tokoro M, Yoshida M, Ogura Y, Nippon Ganka Gakkai zasshi, 115, (8) 681 - 685,   2011年08月, 査読有り
  • Recent advances in intraocular drug delivery systems., Yasukawa T, Tabata Y, Kimura H, Ogura Y, Recent patents on drug delivery & formulation, 5, (1) 1 - 10,   2011年01月, 査読有り
  • Outcomes and Complications of 25-Gauge Transconjunctival Sutureless Vitrectomy for Proliferative Diabetic Retinopathy, Daisuke Ozone, Yoshio Hirano, Jiro Ueda, Tsutomu Yasukawa, Munenori Yoshida, Yuichiro Ogura, OPHTHALMOLOGICA, 226, (2) 76 - 80,   2011年, 査読有り, Purpose: To investigate the feasibility and efficacy of 25-gauge vitrectomy in the treatment of proliferative diabetic retinopathy (PDR). Methods: All patients underwent primary 25-gauge vitrectomy for simple vitreous hemorrhage (VH), fibrovascular proliferation (FVP), or tractional retinal detachment (TD), and were followed for more than 1 month. Final visual outcomes and intraoperative and postoperative complications were evaluated. Results: 167 eyes (138 patients) were used in this study, 65 eyes (39%) with VH, 66 eyes (40%) with FVP, and 36 eyes (21%) with TD. Measured using the mean logarithm of the minimum angle of resolution (logMAR), visual acuity (VA) significantly improved (p < 0.0001). Intraoperative iatrogenic retinal breaks developed in 19 eyes (11%). Concerning postoperative complications, VH in 36 eyes (22%), retinal detachment in 2 eyes (1%), and neovascular glaucoma 12 eyes (7%) were observed. No endophthalmitis developed. Conclusions: Twenty-five-gauge vitrectomy can successfully treat PDR. Clinical outcomes and complications are comparable to those of 20-gauge vitrectomy. Copyright (C) 2011 S. Karger AG, Basel
  • Optical coherence tomography guided peeling of macular epiretinal membrane., Hirano Y, Yasukawa T, Ogura Y, Clinical ophthalmology (Auckland, N.Z.), 5, 27 - 29,   2010年12月, 査読有り
  • [Clinical features and pathogenesis of diabetic maculopathy]., Yasukawa T, Nihon rinsho. Japanese journal of clinical medicine, 68 Suppl 9, 329 - 333,   2010年11月, 査読有り
  • Transient tractional retinal detachment in an eye with retinitis pigmentosa., Hirahara S, Hirano Y, Yasukawa T, Ogura Y, Clinical ophthalmology (Auckland, N.Z.), 4, 1115 - 1118,   2010年10月, 査読有り
  • Bilateral serous retinal detachments associated with accelerated hypertensive choroidopathy., Hirano Y, Yasukawa T, Ogura Y, International journal of hypertension, 2010,   2010年09月, 査読有り
  • Indocyanine green angiography-guided laser photocoagulation combined with sub-Tenon's capsule injection of triamcinolone acetonide for idiopathic macular telangiectasia, Yoshio Hirano, Tsutomu Yasukawa, Yoshimi Usui, Miho Nozaki, Yuichiro Ogura, BRITISH JOURNAL OF OPHTHALMOLOGY, 94, (5) 600 - 605,   2010年05月, 査読有り, Aims Type 2 (perifoveal) telangiectasia often is refractory to treatment, because focal targets such as aneurysms are not detected by fluorescein angiography (FA) in these eyes. The authors evaluated the efficacy of indocyanine green angiography (IA)-guided laser photocoagulation and sub-Tenon's capsule injection of triamcinolone acetonide (STTA) for idiopathic macular telangiectasia. Methods Seven eyes (seven patients; mean age, 72 years) were enrolled, five eyes with type 1 and two eyes with type 2. The mean follow-up was 10.6 months (range 7 to 19). FA and IA were performed with the Heidelberg Retina Angiogram 2. Laser photocoagulation was applied to leaky vessels detected by late-phase IA (wavelength, 577 nm; power, 100-200 mW; spot size, 100-200 mm; and duration, 0.2 s). STTA (20 mg) was injected after photocoagulation. The central macular thickness and macular volume were measured periodically by optical coherence tomography. The logarithm of the minimum angle of resolution (logMAR) visual acuity (VA) was measured. Results IA identified leaky aneurysms or vessels. The final mean logMAR VA and the central macular thickness improved significantly from baseline (p=0.040, p=0.0002, respectively). The VA improved by 0.3 or more logMAR unit in two eyes (29%) and stabilised in five eyes (71%). No adverse effects were reported throughout follow-up. Conclusions IA can detect microangiopathy in eyes with idiopathic macular telangiectasia. IA-guided laser photocoagulation combined with STTA might be effective for treating types 1 and 2 idiopathic macular telangiectasia. Further studies are needed to access the efficacy of IA-guided photocoagulation for treating type 2 telangiectasia.
  • Unilateral Acute Retinal Necrosis 2 Months After Herpes Simplex Encephalitis., Sugitani K, Hirano Y, Yasukawa T, Yoshida M, Ogura Y, Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye, 1 - 5,   2010年03月, 査読有り
  • Medical devices for the treatment of eye diseases., Yasukawa T, Ogura Y, Handbook of experimental pharmacology, (197) 469 - 489,   2010年, 査読有り
  • Intraocular pressure elevation following triamcinolone acetonide administration as related to administration routes., Hirano Y, Ito T, Nozaki M, Yasukawa T, Sakurai E, Yoshida M, Ogura Y, Japanese journal of ophthalmology, 53, (5) 519 - 522,   2009年09月, 査読有り
  • Fundus autofluorescence and fate of glycoxidized particles injected into subretinal space in rabbit age-related macular degeneration model., Hirata M, Yasukawa T, Wiedemann P, Kimura E, Kunou N, Eichler W, Takase A, Sato R, Ogura Y, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 247, (7) 929 - 937,   2009年07月, 査読有り
  • Early-onset macular holes following ruptured retinal arterial macroaneurysms., Sato R, Yasukawa T, Hirano Y, Ogura Y, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 246, (12) 1779 - 1782,   2008年12月, 査読有り
  • Suppressive effect of short-interfering RNA on hyperglycemia-induced expression of intercellular adhesion molecule-1 on cultured vascular endothelial cells., Takase A, Yasukawa T, Kato A, Ogura Y, Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie, 246, (7) 989 - 992,   2008年07月, 査読有り
  • Large blunt scleral rupture without retinal detachment., Takayama K, Yasukawa T, Okada M, Sumida A, Watanabe N, Uchida S, Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye, 39, (3) 242 - 245,   2008年05月, 査読有り
  • Glycoxidized particles mimic lipofuscin accumulation in aging eyes: a new age-related macular degeneration model in rabbits, Tsutomu Yasukawa, Peter Wiedemann, Stefan Hoffmann, Johannes Kacza, Wolfram Eichler, Sheng Wang, Akiko Nishiwaki, Johannes Seeger, Yuichiro Ogura, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 245, (10) 1475 - 1485,   2007年10月, 査読有り, Purpose The biogenesis of drusen, a hallmark of age-related macular degeneration (AMD), is still unclear. Lipofuscin, which extensively accumulates with age in RPE cells, is hardly soluble, derived in part from oxidation byproducts of the photoreceptor outer segments. The purpose of the current study is to develop a new AMD model in rabbits using glycoxidized particles as imitation lipofuscin, and determine whether accumulation of lipofuscin as insoluble material may play a role in drusen biogenesis and other pathogenesis of AMD. Methods To mimic the accumulation of insoluble lipofuscin, glycoxidized microspheres (glycox-MS) were made through a glycoxidation process with albumin and glycolaldehyde, alpha-hydroxy aldehyde. As a control, microspheres made with glutaraldehyde (cMS) and soluble glycoxidized (glycox-) albumin were prepared. Each material was implanted into the subretinal space in rabbits. The implanted area was assessed by funduscopy, fluorescein angiography, histology, and transmission electron microscopy (TEM). Results Compared with control microspheres, glycox-MS stagnated for a prolonged period in the cytoplasm of RPE cells. Eyes implanted with glycox-MS produced drusen-like deposits at a significantly higher frequency, when compared with the controls. Glycox-MS were observed at the margin of or beneath the drusen-like deposits in all cases. In some eyes with glycox-MS, late-onset sub-RPE choroidal neovascularization was observed, while control groups did not have these findings. Conclusions These results suggest that the accumulation of indigestible granules such as lipofuscin in RPE or subsequent depositions toward Bruch's membrane may play a role in drusen biogenesis as a trigger of inflammation or via other mechanisms. This model of AMD may be useful to elucidate drusen biogenesis and pathogenesis of AMD.
  • Copper foreign body in the lens without damage of iris and lens capsule., Tokoro M, Yasukawa T, Okada M, Ogura Y, Uchida S, International ophthalmology, 27, (5) 329 - 331,   2007年10月, 査読有り
  • Flexible UV light guiding system for intraocular laser microsurgery, Stanislaw Schastak, Yousef Yafai, Tsutomu Yasukawa, Yu-Sheng Wang, Georg Hillrichs, Peter Wiedemann, LASERS IN SURGERY AND MEDICINE, 39, (4) 353 - 357,   2007年04月, 査読有り, Background and Objective: Until now, UV lasers could not be applied to vitreoretinal surgery because of the absence of a practical beam guiding system. A flexible, freely mobile hollow core waveguide, capable of delivering UV laser light, was recently developed. We evaluated the feasibility of this UV laser guiding system for vitreoretinal surgery in enucleated porcine and rabbit eyes and in vivo on rabbit retina. Materials and Methods: 193-nm argon fluoride (ArF) excimer laser and a 5th harmonic Nd:YAG laser with the wavelength of 213 nm were used as a light source. A hollow core waveguide was connected to a handpiece with a 20-gauge endoprobe as an instrument for vitreoretinal surgery. Results: Cutting of the retina was possible only with contact technique. With a selected repetition rate of 20 Hz, sharp, full-depth dissection of porcine retinas was achieved 2 only with 1.0 J/cm. With the repetition rate of 50 Hz, even 0.05 j/cm(2) could incise the total thickness of rabbit retina with no histological damage of the underlying retinal pigment epithelium. The ease in using the instrument for vitreoretinal surgery was confirmed by the in vivo experiment. Conclusion: This study revealed the potential use of the new type of the U-V laser scalpel, connected to a hollow core waveguide, to perform precise, "cold," and tractionless cutting during vitreoretinal surgery. Lasers Surg. Med. 39:353-357, 2007. (C) 2007 Wiley-Liss, Inc.
  • Drug delivery from ocular implants., Yasukawa T, Ogura Y, Kimura H, Sakurai E, Tabata Y, Expert opinion on drug delivery, 3, (2) 261 - 273,   2006年03月, 査読有り
  • Characteristics of iris and retinal pigment epithelial cells cultured on collagen type I membranes, G Thumann, A Hueber, S Dinslage, F Schaefer, T Yasukawa, B Kirchhof, Y Yafai, W Eichler, A Bringmann, P Wiedemann, CURRENT EYE RESEARCH, 31, (3) 241 - 249,   2006年03月, 査読有り, Purpose: Transplantation of pigment epithelial cells is a promising treatment modality to repair retinal damage in age-related macular degeneration. For this purpose, it is necessary to establish cell culture techniques that allow acquisition of proper functional and morphological characteristics by the cells to be transplanted. Methods: Primary retinal pigment epithelial (RPE) and iris pigment epithelial (IPE) cells grown to confluence on collagen membranes were examined for morphology, adhesion, proliferation, apoptosis, as well as viability after ex vivo transplantation. Results: Pigment epithelial cells adhere, proliferate, form monolayers, acquire differentiated properties, and remain viable during transplantation to the subretinal space. Conclusions: Pigment epithelial cells cultured on collagen membranes acquire differentiated characteristics and are amenable to be transplanted as cell monolayers.
  • Intraocular sustained drug delivery using implantable polymeric devices, T Yasukawa, Y Ogura, E Sakurai, Y Tabata, H Kimura, ADVANCED DRUG DELIVERY REVIEWS, 57, (14) 2033 - 2046,   2005年12月, 査読有り, Vitreoretinal diseases involving age-related macular degeneration (AMD) are refractory to most topical or systemic drugs. The retina and the vitreous cavity have a unique position regarding pharmacokinetics in that the inner and outer blood retinal barriers separate the retina and vitreous from the systemic circulation. Eye drops achieve minimal therapeutic concentrations in the vitreoretinal tissue. Drug delivery systems are a strategy to address this. Intraocular sustained drug release using implantable devices has been investigated to treat vitreoretinal diseases. Possible targeted diseases include those in which repeated intraocular injections are effective (cytomegalovirus retinitis, uveitis), diseases requiring surgery (proliferative vitreoretinopathy), and chronic diseases (AMD, macular edema, retinitis pigmentosa). Hydrophobic or hydrophilic polymers shaped into a sheet, disc, rod, plug, or a larger device can be implanted into the subretinal space, intrascleral space, vitreous space, peribulbar space, or at the pars plana. Many researchers suggest the feasibility of these implants to treat AMD. (c) 2005 Elsevier B.V. All rights reserved.
  • Impact of endostatin on bFGF-induced proliferation, migration, and matrix metalloproteinase-2 expression/secretion of bovine choroidal endothelial cells, YS Wang, W Eichler, U Friedrichs, Y Yafai, S Hoffmann, T Yasukawa, YN Hui, P Wiedemann, CURRENT EYE RESEARCH, 30, (6) 479 - 489,   2005年06月, 査読有り, Purpose: To investigate the potential role of endostatin, an endogenous angiogenesis inhibitor, in the prevention of choroidal angiogenesis-related disorders. Methods: Bovine choroidal endothelial cells (CEC) were cultured and treated with basic fibroblast growth factor ( bFGF) alone or combined with endostatin at concentrations ranging from 0.1 to 10 mu g/ml. The proliferation and migration of CECs were evaluated by using 3,(4,5-dimethylthiazol-2-yl)-2,5diphenyl tetrazolium bromide (MTT) colorimetric assay and modified Boyden chamber assay, respectively. For evaluating expression and secretion of matrix metalloproteinase-2 ( MMP-2), CEC-conditioned media were subjected to zymography and/or Western blot analysis, and the cells were used for semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analysis. Results: Endostatin did not inhibit bFGF-induced or nonstimulated CEC proliferation ( p > 0.05). The bFGF-induced migration was significantly inhibited by endostatin at concentrations of 1 and 10 mu g/ml ( p < 0.05). The bFGF-upregulated expression of mRNA in CECs and the secretion of MMP-2 protein of CECs were both suppressed by endostatin. Conclusions: Inhibitory effect of endostatin on expression and secretion of MMP-2 and cell migration, but not on proliferation of CECs, could respond to its therapeutic action for choroidal neovascularization-dependent disorders.
  • Preliminary results of development of a single-mode Q-switched Nd : YAG ring laser at 213 nm and its application for the microsurgical dissection of retinal tissue ex vivo, T Yasukawa, Y Yafai, YS Wang, H Dietz, D Molotkov, N Kongratyuk, G Hillrichs, P Wiedemann, SI Schastak, LASERS IN MEDICAL SCIENCE, 19, (4) 234 - 239,   2005年04月, 査読有り, The Nd: YAG laser family offers wide possibilities for surgery applications in medicine. The radiation at 213 nm provides similar tissue effects as compared to 193 nm excimer lasers, but offers considerable practical advantages in the operating room. As such, it is of considerable interest to create single-mode Q-switched fifth harmonic Nd: YAG pulsed lasers with a high coefficient of efficiency and low divergence. Parameters of the ring three-mirror anisotropic cavity TEM00-Nd: YAG laser were calculated on the basis of the analysis of Gaussian beam behavior in the three-mirror ring cavity, with one convex spherical mirror and one intracavity positive lens. On the hand of numerical calculations a prototype of a single-mode Q-switched Nd: YAG-213 nm laser with an output energy of 4 mJ and a beam divergence of 1 mrad has been developed. At a pulse repetition rate of 50 Hz, it has a generation efficiency in the Q-switched mode of 0,6%. A hollow core wave guide is used in combination with a short length of a special fused silica optical fiber to guide the laser beam. Full-depth dissection of rabbit retina ex vivo was achieved at the intensities of 0.18 - 0.05 J/cm(2) and a repetition rate of 50 Hz, with a linear cutting rate of 6 mm/s. Although the retina was completely cut, heat necrosis of the choroid did not occur. We are currently in the process of testing the dissection of retinal tissue during retinotomy, and the formation of holes in the trabecular meshwork in glaucoma surgery.
  • The role of estrogen and estrogen receptor beta in choroidal neovascularization, M Tanemura, N Miyamoto, M Mandai, H Kamizuru, S Ooto, T Yasukawa, M Takahashi, Y Honda, MOLECULAR VISION, 10, (111) 923 - 932,   2004年12月, 査読有り, Purpose: Choroidal neovascularization (CNV) under the age of 50 is more often observed in women than in men. The effects of 17beta-estradiol (E2) on choroidal neovascularization development were investigated both in animal models and cultured cells to see if estrogen receptors (ERs) are involved in the process. Methods: CNV was induced by fundus laser photocoagulation in adult male and female rats. The degree of CNV development was scored and compared between them. Gene expression levels of VEGF receptor 2 (VEGFR2) and ERs after photocoagulation were compared between genders using real time PCR. CNV formation and the gene expressions were also examined in ovariectomized females with and without E2 treatment. The roles of ERs were studied by overexpressing them in human umbilical vein endothelial cells (HUVECs). The localization of estrogen receptorbeta (ERbeta) and VEGFR2 in CNV were studied immunohistochemically. Results: CNV scores were significantly higher in females than in males 14 and 21 days after photocoagulation (<0.05). VEGFR2 and ERbeta gene levels were increased more in females than in males on day 7 (3.4 fold compared to 1.8 fold) and on day 3 (5.8 fold compared to 2.3 fold) after photocoagulation, respectively. Both ERbeta and VEGFR2 gene expressions were additively enhanced by photocoagulation and E2 treatment in ovariectomized females. E2 significantly enhanced VEGFR2 gene expression and cell proliferation in HUVECs overexpressing ERbeta. ERbeta and VEGFR2 are well co-localized in CNV tissue. Conclusions: Estrogen may promote CNV development by increasing VEGFR2 gene expression via ERbeta.
  • Drug delivery systems for vitreoretinal diseases, T Yasukawa, Y Ogura, Y Tabata, H Kimura, P Wiedemann, Y Honda, PROGRESS IN RETINAL AND EYE RESEARCH, 23, (3) 253 - 281,   2004年05月, 査読有り, The eye has an environment that is specific unto itself in terms of pharmacokinetics: the inner and outer blood-retinal barriers separate the retina and the vitreous from the systemic circulation and vitreous body, which physiologically has no cellular components, occupies the vitreous cavity, an inner space of the eye, and reduces practical convection of molecules. Considering this, development of a drug delivery system (DDS) is becoming increasingly important in the treatment of vitreoretinal diseases not only to facilitate drug efficacy but also to attenuate adverse effects. The DDS has three major goals: enhances drug permeation (e.g., iontophoresis and transscleral DDS), controls release of drugs (e.g., microspheres, liposomes, and intraocular implants), and targets drugs (e.g., prodrugs with high molecular weight and immunoconjugates). Comprehensive knowledge of these should lead to development of innovative treatment modalities. (C) 2004 Elsevier Ltd. All rights reserved.
  • Inhibition of experimental choroidal neovascularization in rats by an alpha(v)-integrin antagonist, T Yasukawa, S Hoffmann, W Eichler, U Friedrichs, YS Wang, P Wiedemann, CURRENT EYE RESEARCH, 28, (5) 359 - 366,   2004年05月, 査読有り, Purpose. Integrin alpha(v)beta(3) is predominantly expressed on endothelial cells in choroidal neovascularization (CNV). We evaluated the efficacy of cyclic RGD (Arg-Gly-Asp) peptide, an alpha(v)-integrin antagonist, in a rat model of laser-induced CNV. Methods. We evaluated the effect of cyclic RGD on the adhesion and cell viability of bovine choroidal endothelial cells (BCECs) by cell counting and the trypan blue dye exclusion test. CNV was induced by laser photocoagulation in female Long Evans rats (day 0), followed by intravitreal administration of one dose of cyclic RGD of 200 (n = 9), 100 (n = 10), 50 (n = 4), or 0 mug (n = 9) on days 9 and 11. We assessed the area of CNV by fluorescein angiography and the thickness microscopically on histologic sections. Neovascular vessels were detected by an antibody against factor VIII. Results. Cyclic RGD (0.02 to 200 mug/ml) inhibited adhesion of BCECs in a dose-dependent manner without changing the cell viability (p < 0.01). In eyes treated with two injections of 200 or 100 μg of cyclic RGD peptide, the development of CNV was significantly (p < 0.01) inhibited in the area of leakage on fluorescein angiography. Histologically, the CNV membrane was observed beneath the retina and the factor VIII-positive cells and red blood cells were involved. The thickness of the lesions was significantly (p < 0.01) reduced in eyes that received 200 or 100 μg of RGD. Conclusions. Cyclic RGD effectively inhibited CNV progression in a rat model of laser-induced CNV, suggesting that this α(v)-integrin antagonist may be beneficial in the treatment of CNV.
  • Sustained release of cis-hydroxyproline in the treatment of experimental proliferative vitreoretinopathy in rabbits, T Yasukawa, H Kimura, Y Tabata, H Miyamoto, Y Honda, Y Ogura, GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 240, (8) 672 - 678,   2002年08月, 査読有り, Purpose: To evaluate the efficacy of sustained-release cis-4-hydroxyproline (CHP), a proline analog that inhibits collagen secretion, on experimental proliferative vitreoretinopathy (PVR) in rabbits. Methods: To demonstrate the sustained release of CHP we developed scleral implants weighing 8.5 mg made of a homogeneous mixture of poly(D,L-lactide-co-glycolide) (PLGA) and various doses of CHP. The CHP release profiles were evaluated by high-performance liquid chromatography in vitro. Scleral implants loaded with 20% and 15% of CHP and made from PLGA (copolymer ratios 65/35 and 50/50; mean molecular weights 103,000 and 93,000, respectively) were used to treat experimental PVR and the efficacy was studied. In treated eyes, two PLGA 65/35 implants (n=7), PLGA 50/50 implants (n=6), or a PLGA 65/35 and a PLGA 50/50 implant (n=9) were inserted at the pars plana, followed by PVR induction with autologous fibroblasts. Control eyes (n= 18) received two implants without CHP. Ocular tissue toxicity was evaluated histologically. Results: In vitro release studies demonstrated a triphasic release pattern. The PLGA 65/35 and PLGA 50/50 implants released CHP over 4 and 7 weeks, respectively. The PLGA 65/35 implants decreased the incidence of retinal detachment from 89% (in controls) to 57% on day 28. When both PLGA 65/35 and PLGA 50/50 implants were used, the inhibitory effect was synergistically enhanced (P=0.0034), while implantation with only PLGA 50150 implants had no significant effect on PVR. No toxic reactions were observed. Conclusion: These results suggest that the biodegradable polymeric implants containing CHP represent a potential treatment for PVR.
  • Targeting of interferon to choroidal neovascularization by use of dextran and metal coordination, T Yasukawa, H Kimura, Y Tabata, H Kamizuru, H Miyamoto, Y Honda, Y Ogura, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 43, (3) 842 - 848,   2002年03月, 査読有り, PURPOSE. Bioactive proteins such as interferon (IFN) have been reported to be combined with water-soluble polymers, such as dextran, through metal coordination, without need for complicated procedures. In the current study, the targeting and inhibitory effects of IFN combined with dextran on experimental choroidal neovascularization (CNV) were studied in vivo. METHODS. Interferon (IFN)beta was conjugated to dextran, which has metal-chelating, diethylenetriaminepentaacetic acid (DTPA) residues. Based on metal coordination, conjugation of IFNbeta with DTPA-dextran resulted from simply mixing both substances in an aqueous solution containing Zn2+. The effects of IFNbeta on the proliferation of human umbilical vein endothelial cells (HUVECs) and bovine retinal pigment epithelial cells (BRPECs) were evaluated. To evaluate the activity loss of IFNbeta by conjugation, the effect of the conjugate on HUVECs was compared with that of free IFNbeta. Experimental CNV was induced by subretinal injection of gelatin microspheres containing basic fibroblast growth factor in rabbits. The rabbits with CNV were intravenously treated twice weekly with 7.5 million international units (MIU)/kg per day free IFNbeta (for 4 weeks), with IFNbeta-DTPA-dextran conjugate containing 7.5 (for 2 weeks) or 0.75 (for 4 weeks) MIU/kg per day IFNbeta, or with saline. The effects of these substances were evaluated by fluorescein angiography and histology. To observe the accumulation of conjugate, the doses of IFNbeta in CNV tissues were measured by enzyme-linked immunosorbent assay. RESULTS. IFNbeta inhibited the growth of HUVECs and enhanced the proliferation of BRPECs. The conjugate seemed to preserve approximately 44% of IFNbeta activity. Although both doses of IFNbeta-DTPA-dextran inhibited progression of CNV in rabbits, longer term administration of a lower dose of IFNbeta-DTPA-dextran had a sustained inhibitory effect on progression of CNV (P < 0.05). Histologic studies revealed the inhibitory effect of IFNbeta-DTPA-dextran on progression of CNV. This conjugate prolonged the plasma half-life of IFNbeta and enabled IFNbeta to accumulate in the CNV in rabbits. CONCLUSIONS. In this study, human IFNbeta was successfully used to target CNV, an enhanced antiangiogenic effect was achieved by combining it with dextran, based on metal coordination. This targeted delivery of U-No may have potential as a treatment modality for CNV.
  • Preparation of microspheres and incorporation of lipid hydroperoxide for sustained release studies., Armstrong D, Kimura H, Tamai K, Yasukawa T, Afzal M, Browne RW, Methods in molecular biology (Clifton, N.J.), 196, 313 - 319,   2002年, 査読有り

講演・口頭発表等

  • Automated Detection of Macular Diseases by Optical Coherent Tomography (OCT) and Artificial Intelligence (AI), 安川 力, 3rd Japan-Taiwan Vitreoretinal Joint Meeting,   2018年11月04日
  • 網膜疾患と人工知能AI, 安川 力, 第18回眼科臨床機器研究会,   2018年10月20日
  • 組織プラスミノーゲンアクチベーター・ ラニミズマブ併用療法, 安川 力, 第56回 網膜硝子体学会,   2017年12月02日
  • 糖尿病網膜症における 広角インドシアニングリーン蛍光眼底造影, 安川 力, 第23回日本糖尿病眼学会,   2017年10月27日
  • A possible role of lipid accumulation in Bruch’s membrane in the pathogenesis of age-related macular degeneration, 安川 力, XXII Biennial Meeting of the International Society for Eye Research,   2016年09月26日
  • A Simple, Lens-Sparing Technique to Treat Persisting Hypotonic Maculopathy Secondary to Large Cyclodialysis, 安川 力, EURETINA2016,   2016年09月08日
  • Visual outcomes of polypoidal choroidal vasculopathy without prompt treatments, 安川 力, Club Jules Gonin 2016,   2016年07月06日
  • A New Simple Technique to Treat Persisting Hypotonic Maculopathy Secondary to Wide Cyclodialysis, 安川 力, Vail Winter Vitrectomy Meeting,   2016年02月21日

特許

  • 眼科薬物徐放装置, 安川 力, 特願2016-93496
  • 眼科診断支援装置、眼科診断支援方法、及び眼科診断支援プログラム, 安川 力, 特願2018-166417

受賞

  •   2018年01月, ベストドクターズ社, Best Doctors in Japan2018-2019
  •   2008年12月, 日本網膜硝子体学会, 第一回 Young Investigator's Award
  •   2003年04月, Association for Research in Vision and Ophthalmology, Travel Grant for Annual Meeting
  •   2000年12月, フンボルト財団, 留学助成
  •   2000年04月, 日本アイバンク協会, 留学助成

競争的資金

  • 加齢黄斑変性の病態におけるブルッフ膜への加齢性沈着脂質の役割の解明, 日本学術振興会, 基盤研究C,   2016年04月 - 2019年03月
  • 抗体および生理活性物質の眼内ドラッグデリバリーシステムの開発, 日本学術振興会, 基盤研究C,   2013年04月 - 2016年03月
  • 異常眼底自発蛍光の病理学的意義と加齢黄斑変性発症との関連性の検討, 日本学術振興会, 基盤研究C,   2009年04月 - 2012年03月

教育活動情報

担当経験のある科目

  • 眼科, 名古屋市立大学、京都大学、名古屋工業大学、山口大学


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