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野崎 実穂ノザキ ミホ

所属部署医学研究科視覚科学分野
職名講師
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ホームページURLhttp://www.med.nagoya-cu.ac.jp/ganka.dir/index.html
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Last Updated :2020/06/03

研究者基本情報

学歴

  •  - 1993年, 名古屋市立大学, 医学部
  •  - 1993年, 名古屋市立大学

学位

  • 博士(医学), 名古屋市立大学

所属学協会

  • 日本眼科手術学会
  • 日本糖尿病眼学会
  • 小児眼科学会
  • 日本眼科学会

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

    糖尿病網膜症, 血管内皮増殖因子, 加齢黄斑変性, 血管新生, diabetic retinopathy, VEGF, age-related macular degeneration, angiogenesis, laser photocoagulation, diabetic macular edema (DME), レーザー網膜光凝固, 糖尿病黄斑浮腫

論文

  • Indocyanine green angiography-guided focal navigated laser photocoagulation for diabetic macular edema., 野崎 実穂, Japanese Journal of Ophthalmology, 63, (3) 243 - 254,   2019年05月, 査読有り
  • Less Expansion of Short-Pulse Laser Scars in Panretinal Photocoagulation for Diabetic Retinopathy., Higaki M, Nozaki M, Yoshida M, Ogura Y, Journal of ophthalmology, 2018,   2018年, 査読有り
  • Evaluation of Navigated Laser Photocoagulation (Navilas 577+) for the Treatment of Refractory Diabetic Macular Edema., Kato F, Nozaki M, Kato A, Hasegawa N, Morita H, Yoshida M, Ogura Y, Journal of ophthalmology, 2018,   2018年, 査読有り
  • Suppression of Retinal Neovascularization by Anti-CCR3 Treatment in an Oxygen-Induced Retinopathy Model in Mice, Shuichiro Hirahara, Miho Nozaki, Masaharu Ohbayashi, Norio Hasegawa, Daisuke Ozone, Yuichiro Ogura, OPHTHALMIC RESEARCH, 58, (1) 56 - 66,   2017年, 査読有り, Purpose: To investigate the association between retinal neovascularization and the CC chemokine receptor-3 (CCR3) in a mouse model of oxygen-induced retinopathy (OIR). Methods: An OIR model in C57BL/6J mice was used as a retinal neovascularization model. An enzyme-linked immunosorbent assay was performed to evaluate the chronological change in vascular endothelial growth factor A (VEGF-A) and eotaxin expressions. CCR3 and VEGF subtype expression in the retina was examined using real-time RT-PCR, and CCR3, eotaxin, VEGF-A, and CD31 expression was examined immunohistochemically. A CCR3 neutralizing antibody (Ab) was injected into the vitreous humor on both postnatal days 12 (P12) and 14 (P14). Retinal neovascularizations were quantified by measurement of the percentages of neovascular area. Results: The mean eotaxin and VEGF-A protein level was significantly downregulated at P10 and P12 and was significantly upregulated at P14 and P17 (p < 0.05). CCR3 mRNA expression was significantly upregulated at P12 (p < 0.05). VEGF164 mRNA expression was significantly upregulated at P14 (p < 0.05). The areas of vaso-obliteration and neovascularization were significantly suppressed in anti-CCR3 Abtreated eyes (p < 0.05). Anti-CCR3 Ab treatment suppressed VEGF and eotaxin but not monocyte chemoattractant protein-1. And VEGF 164 mRNA but not VEGF120 mRNA was suppressed by anti-CCR3 Ab treatment. Conclusions: The present data suggest that anti-CCR3 treatment can suppress retinal neovascularization. Anti-CCR3 treatment may have potential as a new therapy for retinopathies with retinal neovascularization such as diabetic retinopathy and retinopathy of prematurity. (C) 2017 S. Karger AG, Basel
  • 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.
  • Characteristics of Polypoidal Choroidal Vasculopathy Evaluated by Optical Coherence Tomography Angiography, Taneto Tomiyasu, Miho Nozaki, Munenori Yoshida, Yuichiro Ogura, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57, (9) OCT324 - OCT330,   2016年07月, 査読有り, PURPOSE. The purpose of this study was to compare the angiographic findings of polypoidal choroidal vasculopathy (PCV) detected by indocyanine green angiography (ICGA) and en face optical coherence tomography angiography (OCTA). METHODS. The study design was a retrospective chart review of 20 eyes with a clinical diagnosis of treatment-naive PCV, seen at Nagoya City University Hospital between December 2014 and January 2016. Indocyanine green angiography was performed with Heidelberg Retina Angiography 2 and OCTA was performed by using Avanti RTVue XR. RESULTS. Twenty eyes of 20 patients (18 male, 2 female) were studied. Average age was 71.9 years. Manual segmentation was required to detect the pathologic lesions of PCV in all cases. The polypoidal lesions were detected in 20 eyes (100%) by ICGA, and in 17 eyes (85%) by OCTA. The number of polypoidal lesions detected by OCTA averaged 2.6 +/- 1.9, with an average of 2.0 +/- 1.1 by ICGA (P < 0.05). The branching vascular network (BVN) was detected in 14 eyes (70%) by ICGA and in 14 eyes (70%) by OCTA. All of the BVNs detected by OCTA were located between the RPE and Bruch's membrane. CONCLUSIONS. Despite the manual segmentation required, en face OCTA enabled us to analyze the angiographic features of PCV combined with longitudinal image (B-scan). En face OCTA may be useful for understanding the pathogenesis of PCV and managing PCV.
  • New Insights Into Microaneurysms in the Deep Capillary Plexus Detected by Optical Coherence Tomography Angiography in Diabetic Macular Edema, Norio Hasegawa, Miho Nozaki, Noriaki Takase, Munenori Yoshida, Yuichiro Ogura, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 57, (9) OCT348 - OCT355,   2016年07月, 査読有り, PURPOSE. To study the association between the distributions of microaneurysms detected by en face optical coherence tomography angiography (OCTA) and diabetic macular edema (DME). METHODS. The study design was a retrospective chart review of 27 patients (33 eyes) with DME. The eyes were scanned using OCTA (6 x 6 mm) and spectral-domain (SD) OCT macular cube. Each of the images of the capillary plexus was overlaid onto the image of the topographic map, and the densities of the microaneurysms were measured by ImageJ software. The association between the distribution of microaneurysms and macular edema was evaluated. RESULTS. For microaneurysms in areas with and without edema, 77.3 +/- 8.1% of these microaneurysms were located in the deep capillary plexuses (DCP). However, in areas of edema where the retinal thickness was more than 400 mu m, 91.3 +/- 9.1% of the microaneurysms were found in the DCP. This difference was statistically significant (P < 0.001). In the macular edema area, there was a significantly higher density of microaneurysms in the DCP compared to the superficial capillary plexuses (1.71/mm(2) vs. 0.17/mm(2), P < 0.001). There was also a significant correlation between the macular volume and the density of microaneurysms in the DCP in edema (r = 0.63, P < 0.001). CONCLUSIONS. Our study demonstrated a high proportion of microaneurysms in the DCP, as well as a novel association between the distributions of microaneurysms detected by OCTA and DME. Results also indicated that microaneurysms located in the DCP contribute to the pathogenesis of DME.
  • 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.
  • Value of OCT Angiography in the Diagnosis of Choroidal Neovascularization Complicating Multiple Evanescence White Dot Syndrome, Miho Nozaki, Satoshi Hamada, Masayo Kimura, Munenori Yoshida, Yuichiro Ogura, OPHTHALMIC SURGERY LASERS & IMAGING RETINA, 47, (6) 580 - 584,   2016年06月, 査読有り, This report describes a 19-year-old patient with the rare association of multiple evanescent white dot syndrome (MEWDS) and choroidal neovascularization (CNV). Despite the initial diagnosis of MEWDS, her vision significantly decreased. Fluorescein angiography showed dye leakage and pooling at the macula, whereas optical coherence tomography (OCT) showed cystoid macular edema and serous neuroepithelial elevation. The dye leakage and pooling made it impossible to diagnose CNV. However, OCT angiography (OCTA) revealed a vascular structure in the outer retina, thereby leading to the CNV diagnosis. Visual acuity improved after an anti-vascular endothelial growth factor injection. OCTA proved to be useful in the diagnosis of CNV.
  • [Diabetic macular edema--pathogenesis, diagnosis and treatment]., Nozaki M, Nihon rinsho. Japanese journal of clinical medicine, 74 Suppl 2, 140 - 147,   2016年04月, 査読有り
  • Human IgG1 antibodies suppress angiogenesis in a target-independent manner., Bogdanovich S, Kim Y, Mizutani T, Yasuma R, Tudisco L, Cicatiello V, Bastos-Carvalho A, Kerur N, Hirano Y, Baffi JZ, Tarallo V, Li S, Yasuma T, Arpitha P, Fowler BJ, Wright CB, Apicella I, Greco A, Brunetti A, Ruvo M, Sandomenico A, Nozaki M, Ijima R, Kaneko H, Ogura Y, Terasaki H, Ambati BK, Leusen JH, Langdon WY, Clark MR, Armour KL, Bruhns P, Verbeek JS, Gelfand BD, De Falco S, Ambati J, Signal transduction and targeted therapy, 1,   2016年, 査読有り
  • Wide-field optical coherence tomography angiography using extended field imaging technique to evaluate the nonperfusion area in retinal vein occlusion., Kimura M, Nozaki M, Yoshida M, Ogura Y, Clinical ophthalmology (Auckland, N.Z.), 10, 1291 - 1295,   2016年, 査読有り
  • ENLARGEMENT OF FOVEAL AVASCULAR ZONE IN DIABETIC EYES EVALUATED BY EN FACE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY., Takase N, Nozaki M, Kato A, Ozeki H, Yoshida M, Ogura Y, Retina (Philadelphia, Pa.), 35, (11) 2377 - 2383,   2015年11月, 査読有り
  • [Evaluation of Diabetic Retinopathy with Ultra-wide Field Fluorescein Angiography]., Tomiyasu T, Hirahara S, Nozaki M, Yoshida M, Ogura Y, Nippon Ganka Gakkai zasshi, 119, (11) 807 - 811,   2015年11月, 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
  • 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, Lukpan Orazbekov, Tsutomu Yasukawa, Yoshio Hirano, Shuntaro Ogura, Hideaki Usui, Miho Nozaki, Yuichiro Ogura, Ophthalmic Surgery Lasers & Imaging Retina, 46, (1) 107 - 110,   2015年01月, 査読有り, The authors present the case of a patient with normal-tension glaucoma and pit-like maculopathy observed by high-definition optical coherence tomography. Surgical management of macular retinoschisis was associated with improved vision and full resolution of intraretinal fluid and macular detachment. The patient had progressive vision loss over 6 months preoperatively; best corrected visual acuity and high-definition optical coherence tomography changes improved postoperatively. Optic disc pit-like maculopathy can occur in patients with normal-tension glaucoma in the absence of obvious congenital anomalies of the disc. The intraretinal fluid might have migrated from the vitreous cavity through a microhole at the optic disc margin or in the area with the nerve fiber defect. Vitrectomy without gas tamponade might lead to anatomic and functional recovery. Further studies are needed to better understand the pathogenesis of this disease.
  • Short pulse laser induces less inflammatory cytokines in the murine retina after laser photocoagulation., Ito A, Hirano Y, Nozaki M, Ashikari M, Sugitani K, Ogura Y, Ophthalmic research, 53, (2) 65 - 73,   2015年, 査読有り
  • IL-18 is not therapeutic for neovascular age-related macular degeneration, Yoshio Hirano, Tetsuhiro Yasuma, Takeshi Mizutani, Benjamin J. Fowler, Valeria Tarallo, Reo Yasuma, Younghee Kim, Ana Bastos-Carvalho, Nagaraj Kerur, Bradley D. Gelfand, Sasha Bogdanovich, Shikun He, Xiaohui Zhang, Miho Nozaki, Ryo Ijima, Hiroki Kaneko, Yuichiro Ogura, Hiroko Terasaki, Hiroshi Nagai, Isao Haro, Gabriel Nunez, Balamurali K. Ambati, David R. Hinton, Jayakrishna Ambati, NATURE MEDICINE, 20, (12) 1372 - 1375,   2014年12月, 査読有り
  • [Comparison of outcomes of conventional laser versus pascal laser for diabetic retinopathy]., Yamakawa M, Nozaki M, Sato R, Morita H, Yoshida M, Ogura Y, Nippon Ganka Gakkai zasshi, 118, (4) 362 - 367,   2014年04月, 査読有り
  • A case of retinopathy of prematurity treated by pattern scan laser photocoagulation., Ota S, Nozaki M, Hirahara S, Hattori T, Yoshida M, Ogura Y, Clinical ophthalmology (Auckland, N.Z.), 8, 1409 - 1412,   2014年, 査読有り
  • [Preference and trends of treatment for diabetic retinopathy in Korea and Japan]., Nozaki M, Suzuma K, Inoue M, Kawasaki R, Kida T, Takamura Y, Nagaoka T, Murakami T, Yoshida S, Korea-Japan Diabetic Retinopathy, Study Group, Nippon Ganka Gakkai zasshi, 117, (9) 735 - 742,   2013年09月, 査読有り
  • Suppression of Laser-Induced Choroidal Neovascularization by a CCR3 Antagonist, Takeshi Mizutani, Masayuki Ashikari, Mayumi Tokoro, Miho Nozaki, Yuichiro Ogura, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 54, (2) 1564 - 1572,   2013年02月, 査読有り, PURPOSE. To evaluate the efficacy of a novel CCR3 antagonist for laser injury-induced choroidal neovascularization (CNV) inmice. METHODS. We evaluated YM-344031, a novel and selective small-molecule CCR3 antagonist. CNV was induced by laser injury in C57BL/6J mice, and its volume was measured after 7 days by confocal microscopy. Leakage from the CNV was also measured after 7 days by fluorescein angiography. The CCR3 antagonist was administered by gavage at 1 hour before and 1 day after the laser injury, or intravitreous injection immediately after the laser injury. After the laser injury, ELISA, Western blot analysis, and real-time RT-PCR for VEGF-A expression in the RPE/choroid, and immunohistochemistry for CCR3, CCL11, Ki67, and Rac1 was performed. RESULTS. Both oral administration and intravitreous injection of YM-344031 significantly suppressed the CNV volume (P < 0.0001 and P < 0.01, respectively). Pathologically significant leakage was significantly less common in YM-344031-injected mice (P < 0.0001). The mean VEGF protein level was significantly increased in vehicle-injected eyes after the laser injury (P < 0.05). Although the YM-344031-injected eyes did not show VEGF-A suppression after the laser injury, VEGF164 mRNA upregulation was significantly suppressed in YM-344031-injected mice (P < 0.05), and intravitreous injection of YM-344031 appeared to suppress CCR3, CCL11 (eotaxin), Ki67, and Rac1 expression after the laser injury. CONCLUSIONS. The present data suggest that the CCR3 antagonist YM-344031 can suppress CNV, via suppression of the upregulation of VEGF164 mRNA in VEGF isoform after the laser injury. Although our findings may warrant further investigation, YM-344031 may have potential as a new therapy for age-related macular degeneration. (Invest Ophthalmol Vis Sci. 2013; 54: 1564-1572) DOI:10.1167/iovs.11-9095
  • Efficient Delivery of siRNA by Atelocollagen in a Murine Laser-Induced Choroidal Neovascularization Model, Yuya Ito, Miho Nozaki, Kazuhiko Sugitani, Masayuki Ashikari, Yoshio Hirano, Yuichiro Ogura, OPHTHALMOLOGICA, 230, (4) 215 - 221,   2013年, 査読有り, Purpose: Previous studies have shown that small interfering RNAs (siRNAs) could suppress angiogenesis via stimulation of toll-like receptor-3 (TLR3). The purpose of this study was to determine the efficacy of atelocollagen to deliver siRNA without TLR3 stimulation in the laser-induced choroidal neovascularization (CNV) model. Methods: CNV was induced by laser injury in C57BL/6J mice and volumes were measured 7 days later. Nontargeted siRNA, 21-nucleotide (nt) siRNA-Luc (Luciferase) and 21-nt siRNA-Vegfa were injected into the vitreous following injury. Atelocollagen was incubated with naked 21-nt siRNAs before injection. To block TLR3 endosomal activity, chloroquine was injected intravitreously after laser injury. Results: The mean CNV volumes were significantly smaller in the naked siRNA-Luc, naked siRNA-Vegfa, or siRNA-Vegfa/atelocollagen complex compared with PBS, atelocollagen or siRNA-Luc/atelocollagen complex-injected mice (p < 0.05). Conclusion: These findings demonstrate that atelocollagen may deliver siRNA without nonspecific TLR3 stimulation in the murine laser-CNV model. (C) 2013 S. Karger AG, Basel
  • [Age-related macular degeneration]., Nozaki M, Nihon rinsho. Japanese journal of clinical medicine, 70 Suppl 8, 647 - 651,   2012年11月, 査読有り
  • [Pathology of diabetic retinopathy]., Nozaki M, Ogura Y, Nihon rinsho. Japanese journal of clinical medicine, 68 Suppl 9, 224 - 227,   2010年11月, 査読有り
  • Suppression of Laser-Induced Choroidal Neovascularization by Nontargeted siRNA, Masayuki Ashikari, Mayumi Tokoro, Masahiro Itaya, Miho Nozaki, Yuichiro Ogura, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 51, (7) 3820 - 3824,   2010年07月, 査読有り, PURPOSE. To investigate the effect of nontargeted siRNAs on vascular leakage and vascular endothelial growth factor (VEGF)-A expression in the development of choroidal neovascularization (CNV). METHODS. Nontargeted siRNAs were 21-nt (nucleotides) siRNA-Luc (Luciferase) or 16-nt siRNA-Luc. Targeted 21-nt siRNA-Vegfa or phosphate-buffered saline (PBS) was used for comparison. Laser photocoagulation was used to induce CNV in wild-type C57BL/6J mice; 7 days later, vascular leakage was determined by fluorescein angiography, and CNV volumes were measured by confocal microscopy. Expression of VEGF-A in the retinal pigment epithelium (RPE)/choroid was quantified by ELISA 3 days after photocoagulation. RESULTS. Pathologically significant leakage developed in most of the 16nt-siRNA-Luc- or PBS-injected mice but in significantly fewer 21nt-siRNA-Luc- and 21nt-siRNA-Vegfa-injected mice (P = 0.0004, P = 0.0001, respectively). CNV volume in 21-nt siRNA-Luc- and 21nt-siRNA-Vegfa-injected eyes was significantly lower than in PBS-injected eyes (P = 0.0124, P = 0.0040, respectively). CNV volume was not suppressed by 16-nt siRNA-Luc injection (P = 0.7700). The mean VEGF protein level decreased significantly in the 21nt-siRNA-Luc- and 21nt-siRNA-Vegfa-injected eyes compared with PBS-injected eyes 3 days after laser photocoagulation (P = 0.0011, P = 0.0063, respectively). The 16nt-siRNA-Luc-injected eyes did not show VEGF-A suppression 3 days after laser photocoagulation (P = 0.3177). Between 21-nt siRNA-Luc- and 21nt-siRNA-Vegfa-injected eyes, there were no significant differences in CNV volume, the VEGF-A level, or pathologic leakage detected by fluorescein. CONCLUSIONS. These data suggest that nontarget 21nt-siRNA can suppress laser-induced choroidal neovascularization anatomically and functionally through VEGF suppression. (Invest Ophthalmol Vis Sci. 2010;51:3820-3824) DOI:10.1167/iovs.09-5121
  • 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.
  • Intraocular pressure elevation following triamcinolone acetonide administration as related to administration routes, Yoshio Hirano, Takeshi Ito, Miho Nozaki, Tsutomu Yasukawa, Eiji Sakurai, Munenori Yoshida, Yuichiro Ogura, JAPANESE JOURNAL OF OPHTHALMOLOGY, 53, (5) 519 - 522,   2009年09月, 査読有り, To evaluate the incidence and risk factors of intraocular pressure (IOP) elevation following triamcinolone acetonide (TA) administration. In this retrospective observational case series, patients (224 eyes of 202 patients) with diffuse diabetic macular edema (66 eyes), branch retinal vein occlusion (39 eyes), central retinal vein occlusion (25 eyes), exudative age-related macular degeneration (49 eyes), myopic choroidal neovascularization (10 eyes), uveitis (30 eyes), or other conditions (5 eyes) were administered an intravitreal or posterior sub-Tenon capsule injection, or both, of TA. Sub-Tenon capsule injection was performed on 106 eyes (STTA group). Intravitreal injection was performed on 118 eyes (IVTA group), of which 85 eyes underwent simultaneous intravitreal and sub-Tenon capsule injections. Mean follow-up after TA administration was 15.9 +/- 10.4 (range, 3-39) months. The sub-Tenon capsule injection and intravitreal injection of TA were compared with respect to the frequency of IOP elevation and the time between TA administration and the initial IOP elevation, and the possible risk factors responsible for IOP elevation were identified. There was no significant difference in frequency of IOP > 21 mmHg between the STTA group and the IVTA group (P = 0.0588). There was, however, a significant difference in the frequency of IOP > 30 mmHg between the two groups (P = 0.0004). In the IVTA group, more patients needed antiglaucoma medication than in the STTA group (P = 0.0052). The incidence rate of IOP elevation within 1 week after TA administration in the IVTA group was significantly higher than in the STTA group (P = 0.0154). Risk factors for IOP elevation included higher baseline IOP (P < 0.0001), younger patients (P = 0.0095), and simultaneous administration of sub-Tenon capsule and intravitreal injections (P = 0.0228). Careful follow-up of IOP is required after TA injections.
  • CCR3 is a target for age-related macular degeneration diagnosis and therapy, Atsunobu Takeda, Judit Z. Baffi, Mark E. Kleinman, Won Gil Cho, Miho Nozaki, Kiyoshi Yamada, Hiroki Kaneko, Romulo J. C. Albuquerque, Sami Dridi, Kuniharu Saito, Brian J. Raisler, Steven J. Budd, Pete Geisen, Ariel Munitz, Balamurali K. Ambati, Martha G. Green, Tatsuro Ishibashi, John D. Wright, Alison A. Humbles, Craig J. Gerard, Yuichiro Ogura, Yuzhen Pan, Justine R. Smith, Salvatore Grisanti, M. Elizabeth Hartnett, Marc E. Rothenberg, Jayakrishna Ambati, NATURE, 460, (7252) 225 - U87,   2009年07月, 査読有り, Age-related macular degeneration (AMD), a leading cause of blindness worldwide, is as prevalent as cancer in industrialized nations. Most blindness in AMD results from invasion of the retina by choroidal neovascularisation (CNV). Here we show that the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with AMD, and that despite the expression of its ligands eotaxin-1, -2 and -3, neither eosinophils nor mast cells are present in human CNV. Genetic or pharmacological targeting of CCR3 or eotaxins inhibited injury-induced CNV in mice. CNV suppression by CCR3 blockade was due to direct inhibition of endothelial cell proliferation, and was uncoupled from inflammation because it occurred in mice lacking eosinophils or mast cells, and was independent of macrophage and neutrophil recruitment. CCR3 blockade was more effective at reducing CNV than vascular endothelial growth factor A (VEGF-A) neutralization, which is in clinical use at present, and, unlike VEGF-A blockade, is not toxic to the mouse retina. In vivo imaging with CCR3-targeting quantum dots located spontaneous CNV invisible to standard fluorescein angiography in mice before retinal invasion. CCR3 targeting might reduce vision loss due to AMD through early detection and therapeutic angioinhibition.
  • Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth, Won Gil Cho, Romulo J. C. Albuquerque, Mark E. Kleinman, Valeria Tarallo, Adelaide Greco, Miho Nozaki, Martha G. Green, Judit Z. Baffi, Balamurali K. Ambati, Massimo De Falco, Jonathan S. Alexander, Arturo Brunetti, Sandro De Falco, Jayakrishna Ambati, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 106, (17) 7137 - 7142,   2009年04月, 査読有り, Neovascularization in response to tissue injury consists of the dual invasion of blood (hemangiogenesis) and lymphatic (lymphangiogenesis) vessels. We reported recently that 21-nt or longer small interfering RNAs (siRNAs) can suppress hemangiogenesis in mouse models of choroidal neovascularization and dermal wound healing independently of RNA interference by directly activating Toll-like receptor 3 (TLR3), a double-stranded RNA immune receptor, on the cell surface of blood endothelial cells. Here, we show that a 21-nt nontargeted siRNA suppresses both hemangiogenesis and lymphangiogenesis in mouse models of neovascularization induced by corneal sutures or hindlimb ischemia as efficiently as a 21-nt siRNA targeting vascular endothelial growth factor-A. In contrast, a 7-nt nontargeted siRNA, which is too short to activate TLR3, does not block hemangiogenesis or lymphangiogenesis in these models. Exposure to 21-nt siRNA, which we demonstrate is not internalized unless cell-permeating moieties are used, triggers phosphorylation of cell surface TLR3 on lymphatic endothelial cells and induces apoptosis. These findings introduce TLR3 activation as a method of jointly suppressing blood and lymphatic neovascularization and simultaneously raise new concerns about the undesirable effects of siRNAs on both circulatory systems.
  • [Incidence of posterior subcapsular cataract progression after triamcinolone acetonide administration]., Yoshimura M, Hirano Y, Nozaki M, Yoshida M, Ogura Y, Nippon Ganka Gakkai zasshi, 112, (9) 786 - 789,   2008年09月, 査読有り
  • Sequence- and target-independent angiogenesis suppression by siRNA via TLR3., Kleinman ME, Yamada K, Takeda A, Chandrasekaran V, Nozaki M, Baffi JZ, Albuquerque RJ, Yamasaki S, Itaya M, Pan Y, Appukuttan B, Gibbs D, Yang Z, Karikó K, Ambati BK, Wilgus TA, DiPietro LA, Sakurai E, Zhang K, Smith JR, Taylor EW, Ambati J, Nature, 452, (7187) 591 - 597,   2008年04月, 査読有り
  • Toward a higher fidelity model of AMD., Raisler BJ, Nozaki M, Baffi J, Hauswirth WW, Ambati J, Advances in experimental medicine and biology, 613, 185 - 192,   2008年, 査読有り
  • Upregulation of VEGF in murine retina via monocyte recruitment after retinal scatter laser photocoagulation, Masahiro Itaya, Eiji Sakurai, Miho Nozaki, Kiyoshi Yamada, Satoshi Yamasaki, Kiyofumi Asai, Yuichiro Ogura, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 48, (12) 5677 - 5683,   2007年12月, 査読有り, PURPOSE. This study was conducted to determine changes in the expression of vascular endothelial growth factor (VEGF) in murine retina after retinal scatter laser photocoagulation. METHODS. Photocoagulation (PHC) was performed on wild-type C57BL/6J mice using a diode laser, and the eyes were enucleated 1, 2, 3, 4, 7, and 14 days after laser treatment. VEGF and monocyte chemoattractant protein (MCP)-1 levels in the sensory retina and retinal pigmented epithelial (RPE) cells in both tissues were measured by ELISA. The VEGF mRNA was measured by real-time RT-PCR. Leukocyte infiltration into the RPE-choroid was determined by flow cytometry. VEGF comparisons between mice subjected to PHC and those treated with monocyte recruitment inhibitor (anti-MCP-1) were performed and statistically analyzed. The expression of VEGF and MCP-1 in the retina was determined by immunohistochemistry. RESULTS. VEGF protein levels significantly increased 1 day after PHC in both the RPE-choroid and the sensory retina. VEGF concentrations were maximum at day 3 after photocoagulation and stayed elevated until day 7. The number of choroid-infiltrating macrophages was markedly increased in mice with laser treatment compared with those without laser treatment. VEGF expression decreased after treatment with neutralized antibody to monocyte recruitment. We demonstrate that MCP-1 expression in the retina increased markedly after scatter laser photocoagulation by immunohistochemistry and ELISA. CONCLUSIONS. Retinal scatter laser photocoagulation induced upregulation of VEGF in the sensory retina and RPE-choroid at an early period. The authors speculate that the major source of VEGF in the retina after retinal scatter laser photocoagulation is the recruited monocytes.
  • A case of adult limbal xanthogranuloma, Megumi Hirata, Miho Nozaki, Hironori Ozeki, Fumisato Hirata, Yuichiro Ogura, JAPANESE JOURNAL OF OPHTHALMOLOGY, 51, (4) 302 - 304,   2007年07月, 査読有り
  • Tailor-made orbitocranioplasty for a sphenorbital encephalocele presenting as pulsatile exophthalmos - Case report, Hiroyuki Katano, Noritaka Aihara, Yotaro Takeuchi, Miho Nozaki, Kazuo Yamada, JOURNAL OF NEUROSURGERY, 106, (2) 126 - 130,   2007年02月, 査読有り, Basal encephaloceles account for only 1.5% of all encephaloceles. Within this group, the sphenorbital type is quite rare but causes herniation of the brain into the orbit, leading to pulsatile exoplithalmos and disturbance of visual acuity. The authors present a case of successful orbitocranioplasty for a sphenorbital encephalocele in which they used a skull model in preparation for the operation. A plaster skull model was made from 3D computed tomography (CT) data obtained in a 6-year-old girl with a sphenorbital encephalocele to determine the appropriate size and shape of an implant for repair of the malformation. A hydroxyapatite ceramic implant with high affinity to autologous bone was designed to cover the defect and simultaneously to enlarge the volume of the orbit as well as allow rigid fixation. Postoperative 3D CT scanning demonstrated good placement of the implant, and the patient's pulsatile exophthalmos diminished immediately. The patient's postoperative condition has been good, and she has exhibited no neurological deficit or deformity of the skull around the cranioplasty 30 months after the operation. A skull model using 3D CT data is useful for determining the most appropriate strategy for reconstruction. Hydroxyapatite ceramic implants have high affinity to autologous bone and thus are suitable for children. In cases such as the present one, however, the patient should be observed carefully to ensure that there is not an imbalance between the implant and the still growing autologous skull.
  • Corneal avascularity is due to soluble VEGF receptor-1, Balamurali K. Ambati, Miho Nozaki, Nirbhai Singh, Atsunobu Takeda, Pooja D. Jani, Tushar Suthar, Romulo J. C. Albuquerque, Elizabeth Richter, Eiji Sakurai, Michael T. Newcomb, Mark E. Kleinman, Ruth B. Caldwell, Qing Lin, Yuichiro Ogura, Angela Orecchia, Don A. Samuelson, Dalen W. Agnew, Judy St. Leger, W. Richard Green, Parameshwar J. Mahasreshti, David T. Curiel, Donna Kwan, Helene Marsh, Sakae Ikeda, Lucy J. Leiper, J. Martin Collinson, Sasha Bogdanovich, Tejvir S. Khurana, Masabumi Shibuya, Megan E. Baldwin, Napoleone Ferrara, Hans-Peter Gerber, Sandro De Falco, Jassir Witta, Judit Z. Baffi, Brian J. Raisler, Jayakrishna Ambati, NATURE, 443, (7114) 993 - 997,   2006年10月, 査読有り, Corneal avascularity - the absence of blood vessels in the cornea is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders(1-4). But the molecular underpinnings of the avascular phenotype have until now remained obscure(5-10) and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap(11) by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6(+/-) mice(12,13) and Pax6(+/-) patients with aniridia(14) are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6(+/-) mice. Manatees, the only known creatures uniformly to have vascularized corneas(15), do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals ( dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.
  • [Incidence and risk factors of intraocular pressure elevation after triamcinolone acetonide administration for macular disorders]., Ito T, Nozaki M, Ogura Y, Nippon Ganka Gakkai zasshi, 110, (5) 379 - 383,   2006年05月, 査読有り
  • Drusen complement components C3a and C5a promote choroidal neovascularization, M Nozaki, BJ Raisler, E Sakurai, JV Sarma, Barnum, SR, JD Lambris, Y Chen, K Zhang, BK Ambati, JZ Baffi, J Ambati, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 103, (7) 2328 - 2333,   2006年02月, 査読有り, Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in industrialized nations, affecting 30-50 million people worldwide. The earliest clinical hallmark of AMD is the presence of drusen, extracellular deposits that accumulate beneath the retinal pigmented epithelium. Although drusen nearly always precede and increase the risk of choroidal neovascularization (CNV), the late vision-threatening stage of AMD, it is unknown whether drusen contribute to the development of CNV. Both in patients with AMD and in a recently described mouse model of AMD, early subretinal pigmented epithelium deposition of complement components C3 and C5 occurs, suggesting a contributing role for these inflammatory proteins in the development of AMD. Here we provide evidence that bioactive fragments of these complement components (C3a and C5a) are present in drusen of patients with AMD, and that C3a and C5a induce VEGF expression in vitro and in vivo. Further, we demonstrate that C3a and C5a are generated early in the course of laser-induced CNV, an accelerated model of neovascular AMD driven by VEGF and recruitment of leukocytes into the choroid. We also show that genetic ablation of receptors for C3a or C5a reduces VEGF expression, leukocyte recruitment, and CNV formation after laser injury, and that antibody-mediated neutralization of C3a or C5a or pharmacological blockade of their receptors also reduces CNV. Collectively, these findings establish a mechanistic basis for the clinical observation that drusen predispose to CNV, revealing a role for immunological phenomena in angiogenesis and providing therapeutic targets for AMD.
  • Loss of SPARC-mediated VEGFR-1 suppression after injury reveals a novel antiangiogenic activity of VEGF-A, M Nozaki, E Sakurai, BJ Raisler, JZ Baffi, J Witta, Y Ogura, RA Brekken, EH Sage, BK Ambati, J Ambati, JOURNAL OF CLINICAL INVESTIGATION, 116, (2) 422 - 429,   2006年02月, 査読有り, VEGF-A promotes angiogenesis in many tissues. Here we report that choroidal neovascularization (CNV) incited by injury was increased by excess VEGF-A before injury but was suppressed by VEGF-A after injury. This unorthodox antiangiogenic effect was mediated via VEGFR-1 activation and VEGFR-2 deactivation, the latter via Src homology domain 2-containing (SH2-containing) tyrosine phosphatase-1 (SHP-1). The VEGFR-1-specific ligand placental growth factor-1 (PlGF-1), but not VEGF-E, which selectively binds VEGFR-2, mimicked these responses. Excess VEGF-A increased CNV before injury because VEGFR-1 activation was silenced by secreted protein, acidic and rich in cysteine (SPARC). The transient decline of SPARC after injury revealed a temporal window in which VEGF-A signaling was routed principally through VEGFR-1. These observations indicate that therapeutic design of VEGF-A inhibition should include consideration of the level and activity of SPARC.
  • Suppression of laser-induced choroidal neovascularization by posterior sub-tenon administration of triamcinolone acetonide., Kato A, Kimura H, Okabe K, Okabe J, Kunou N, Nozaki M, Ogura Y, Retina (Philadelphia, Pa.), 25, (4) 503 - 509,   2005年06月, 査読有り
  • Scleral plug of biodegradable polymers containing tacrolimus (FK506) for experimental uveitis, E Sakurai, M Nozaki, K Okabe, N Kunou, H Kimura, Y Ogura, INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 44, (11) 4845 - 4852,   2003年11月, 査読有り, PURPOSE. To evaluate the efficacy of a biodegradable polymeric scleral plug containing the immunosuppressive agent, FK506, in a rabbit model for experimental uveitis. METHODS. The scleral plugs were prepared by dissolving poly(DL-lactide-co-glycolide; PLGA) and FK506 (weight, 8.5 mg; length, 5 mm; 1% FK506). The release of FK506 was evaluated in vitro by spectrophotometry on days 1, 3, 7, 14, 21, and 35. In vivo, FK506 concentrations of the vitreous were measured by high performance liquid chromatography 2 and 4 weeks after intravitreous plug implantation in pigmented rabbits. Sixteen pigmented rabbits were immunized twice subcutaneously with 10 mg of Mycobacterium tuberculosis H37Ra antigen. Twelve days later, the right eyes of all rabbits were challenged with an intravitreal injection of 50 mug of antigen. After the first challenge, the 16 eyes of 16 pigmented rabbits were divided into two groups. Scleral plugs were implanted into the vitreous of the right eye of eight rabbits. Eight control rabbi's received a sham device. The aqueous protein concentrations and cell counts were determined on postchallenge days 7, 14, and 28. To simulated chronic inflammation, the eyes were rechallenged with intravitreal antigen on day 14 and were observed for 1 month. Inflammation of the anterior chamber and the vitreous were graded clinically by two masked observers. Retinal function was evaluated by electroretinography (ERG) and histologic examination. RESULTS. Clinical scores (anterior chamber cells, flare, and vitreous opacity) showed that treated eyes had significantly less inflammation than untreated eyes (P < 0.001). Quantitative analysis of inflammatory cells (P < 0.001) and protein concentrations (P < 0.0001) in the anterior chamber showed significant decreases in treated eyes. Histopathologic examination showed marked inflammation and tissue disorganization in the untreated eyes. No retinal toxicity was detected, histopathologically and electroretinographically. After antigen rechallenge, inflammation in experimental eyes was still less than in control eyes. CONCLUSIONS. Intravitreal sustained-release of FK506 from a biodegradable polymeric scleral plug was highly effective in suppressing the inflammation of experimental uveitis in a rabbit model for at least 6 weeks. This device may be useful in the management of patients with severe chronic uveitis.
  • [A case of peritoneal malignant mesothelioma]., Nozaki M, Suzuki T, Takahashi H, Nishimura S, Sakurabayashi S, Yoshino K, Hirano M, Kawauchi N, Ogawa M, Suzuki T, Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology, 100, (5) 610 - 612,   2003年05月, 査読有り
  • Late-onset laser in situ keratomileusis (LASIK) flap dehiscence during retinal detachment surgery, E Sakurai, M Okuda, M Nozaki, Y Ogura, AMERICAN JOURNAL OF OPHTHALMOLOGY, 134, (2) 265 - 266,   2002年08月, 査読有り, PURPOSE: To report a case of laser in situ keratomileusis (LASIK) flap dehiscence during retinal detachment surgery 7 months after uneventful refractive surgery. DESIGN: Interventional case report. METHODS: A 47-year-old man noticed a defect of the upper visual field in his right eye 7 months after a LASIK procedure. The fundus showed rhegmatogenous retinal detachment, and a scleral buckling procedure was performed. During the buckling procedure, the corneal flap became detached. RESULTS: At completion of the buckling procedure, the detached corneal flap was carefully raised and the ex. posed corneal stroma was cleansed of any residual epithelial cells or red blood cells with irrigation using balanced salt solution. One day after the operation, the LASIK flap was repositioned, the cornea had cleared, and the retina was reattached. CONCLUSIONS: As LASIK increases in popularity, the complication we have reported may become more common. We suggest that a retinal detachment surgery should be performed with careful avoidance of corneal trauma even if a long time has passed since the LASIK procedure. (C) 2002 by Elsevier Science Inc. All rights reserved.
  • Optical coherence tomographic findings of the anterior segment after nonpenetrating deep sclerectomy, M Nozaki, H Kimura, M Kojima, Y Ogura, AMERICAN JOURNAL OF OPHTHALMOLOGY, 133, (6) 837 - 839,   2002年06月, 査読有り, PURPOSE: To evaluate the efficacy of optical coherence tomography for the analysis of anterior segment after glaucoma surgery. DESIGN: Interventional case report. METHODS: In a 79-year-old man with primary open angle glaucoma, optical coherence tomography was performed on the left eye after nonpenetrating deep sclerectomy. RESULTS: Optical coherence tomography showed thing ning of the conjunctiva over the filtering bleb, presence of a space under the scleral flap that is considered as a take, and presence of fibrous tissue in the bleb. CONCLUSION: This case indicates that optical coherence tomography, a noninvasive, noncontact optical imaging modality, may be useful for analysis of the anterior segment after glaucoma surgery. (C) 2002 by Elsevier Science Inc. All rights reserved.
  • Enhanced expression of adhesion molecules of the retinal vascular endothelium in spontaneous diabetic rats, M Nozaki, Y Ogura, Y Hirabayashi, Y Saishin, S Shimada, OPHTHALMIC RESEARCH, 34, (3) 158 - 164,   2002年05月, 査読有り, Otsuka Long-Evans Tokushima Fatty (OLETF) rats are a spontaneously diabetic strain with clinical features resembling those of human noninsulin-dependent diabetes mellitus. These rats show increased leukocyte entrapment in the retina. The present study was designed to investigate the immunolocalization of intercellular adhesion molecules-1 (ICAM-1) and P-selectin in the retinas of OLETF rats. Four 72-week-old male OLETF rats and 4 age- and sex-matched Long-Evans Tokushima Otsuka (LETO) control rats were used. Western blot analysis and immunohistochemical study were performed using an anti-P-selectin monoclonal antibody (mAb) and an anti-ICAM-1 mAb. Western blot analysis showed increased expression of both ICAM-1 and P-selectin in the retinas of OLETF rats. Immunohistochemically, OLETF rats expressed greater amounts of ICAM-1 and P-selectin in the retinal vascular endothelium than did LETO rats. These findings demonstrated the upregulation of ICAM-1 and P-selectin in the retina of OLETF rats. The enhanced expression of these adhesion molecules might participate in the pathogenesis of early diabetic microangiopathy in the retina. Copyright (C) 2002 S. Karger AG, Basel.

MISC

  • 小眼球症マウスにおける眼瞼発生過程の組織学的検索, 日本眼科学会雑誌, 102, (8) 540 - 544,   1998年
  • Histological Studies in the Developing Eyelids of Congenital Microphthalmic(Cts)Mice, Journal of Japanese Ophthalmological Society, 102, (8) 540 - 544,   1998年
  • 合眼症の1例, 日本眼科紀要, 47,   1996年
  • 全身奇形を合併したPeters奇形の1例, 臨床眼科, 50,   1996年
  • A case of synophthalmia, Folia Ophthalmologica Japonica, 47,   1996年
  • A case of Peter's anomaly with systemic malformations, Japanese Journal of Clinical Ophthalmology, 50,   1996年
  • Nontargeted siRNA suppresses Laser -induced choroidal neovascularization
  • Nontargeted siRNA suppresses Laser -induced choroidal neovascularization, Invest Ophthalmol Vis Sci

競争的資金

  • siRNAによる非特異的血管新生抑制
  • 網膜中心窩はなぜ無血管なのか
  • 加齢黄斑変性の病態解明
  • 糖尿病ラット網膜における接着分子
  • 小眼球症マウスにおける眼瞼発生過程の組織学的・組織化学的研究
  • 眼先天異常の組織学的・組織化学的研究
  • Enhanced expression of adhesion molecules of the retinal vascular endothelium in diabetic rats
  • Histological and histochemical studies in the developing eyelid of experimental microphthalmic mice.
  • Histological and histochemical studies on the developmental process of ocular malformations


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