Updated on 2025/03/11

写真a

 
UTSUNOMIYA Tsugiaki
 
Organization
Hospital Clinical Departments Ophthalmology
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Degree

  • 博士 ( 2017.3   旭川医科大学 )

Research Areas

  • Life Science / Ophthalmology

Papers

  • Assessing effects of mechanical stimulation of fluid shear stress on inducing matrix Metalloproteinase-9 in cultured corneal epithelial cells. International journal

    Tsugiaki Utsunomiya, Akihiro Ishibazawa, Takafumi Yoshioka, Young-Seok Song, Koichi Yoshida

    Experimental eye research   234   109571 - 109571   2023.9

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    Blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells. Therefore, we evaluated whether fluid shear stress affects matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human corneal epithelial cells (HCECs). No other study has shown the influence of fluid shear stress on HCECs regarding mRNA expression and the protein levels of MMPs. Cultured HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) for 12 and 24 h with the parallel-plate type of flow chamber. Gene expression of MMPs and TIMPs was measured by real-time polymerase reaction. Concentrations of MMP-1 and MMP-9 in cell lysates were determined using bead-based amplified luminescent proximity homogenous assay-linked immunosorbent assay. The expression of MMP-9 and MMP-1 in HCECs exposed to low and high flow for 12 and 24 h, respectively, increased significantly compared with those under static conditions. The expression of MMP-9 in the cells exposed to high flow for 24 h increased significantly compared with those under static and low flow conditions. Levels of MMP-9 in cell lysates exposed to fluid flow for 24 h were elevated significantly with increasing shear stress. Fluid shear stress exerted on HCECs affected MMPs, which was associated with inflammation and pathogenesis. Mechanical stress induced by blinking might influence expression of MMPs on the ocular surface. Further studies are warranted to establish the molecular mechanism of shear stress-induced alternations of MMPs.

    DOI: 10.1016/j.exer.2023.109571

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  • Assessing effects of mechanical stimulation of fluid shear stress on inducing matrix Metalloproteinase-9 in cultured corneal epithelial cells Reviewed

    Tsugiaki Utsunomiya, Akihiro Ishibazawa, Takafumi Yoshioka, Young-Seok Song, Koichi Yoshida

    Experimental Eye Research   2023.7

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    DOI: doi: 10.1016/j.exer.2023.109571.

  • Extracellular matrix gene expression in human trabecular meshwork cells following mechanical fluid flow stimulation Reviewed

    Koichi Yoshida, Motofumi Kawai, Tsugiaki Utsunomiya, Akihiro Ishibazawa, Young-Seok Song, Mariana Sayuri Udo, Yoshikazu Tasaki, Akitoshi Yoshida.

    International Journal of Ophthalmology   2022.3

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  • Extracellular matrix gene expression in human trabecular meshwork cells following mechanical fluid flow stimulation. International journal

    Koichi Yoshida, Motofumi Kawai, Tsugiaki Utsunomiya, Akihiro Ishibazawa, Young-Seok Song, Mariana Sayuri B Udo, Yoshikazu Tasaki, Akitoshi Yoshida

    International journal of ophthalmology   15 ( 3 )   388 - 393   2022

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    AIM: To investigate changes in extracellular matrix (ECM) gene expression in human trabecular meshwork (HTM) cells in response to mechanical fluid flow stimulation. METHODS: HTM cells were grown on a glass plate coated with 0.02% type I collagen (COL) and exposed to shear stress (0, 0.2, 1.0 dyne/cm2) for 12h. Changes in genes related to the ECM were evaluated by real-time reverse transcriptase-polymerase chain reaction. Phosphorylation of Smad2 protein was investigated by Western blotting. RESULTS: After mechanical stimulation, COL type 4 alpha 2, COL type 6 alpha 1, and fibronectin-1 mRNA were significantly higher than the static control (P<0.05, <0.05, and <0.01, respectively). The metalloproteinase-2 and plasminogen activator inhibitor-1 mRNA were significantly higher than the static control (P<0.05 and <0.01, respectively), while the differences in the tissue inhibitors of metalloproteinases-2 mRNA were not significant. The phosphorylation of Smad2 levels was significantly higher compared to the static control cells. CONCLUSION: Changes in the expressions of genes associated ECM metabolism result in HTM cells after mechanical stimulation. The mechanical stimulation of the aqueous humor to the trabecular meshwork may promote ECM turnover and contribute to intraocular pressure homeostasis.

    DOI: 10.18240/ijo.2022.03.03

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  • Effects of diquafosol ophthalmic solution on quality of life in dry eye assessed using the Dry Eye-related Quality-of-life Score Questionnaire: effectiveness in patients while reading and using visual display terminals. Reviewed

    Utsunomiya T, Kawahara A, Hanada K, Yoshida A.

    Cornea   2017.8

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  • Effects of Diquafosol Ophthalmic Solution on Quality of Life in Dry Eye Assessed Using the Dry Eye-Related Quality-of-Life Score Questionnaire: Effectiveness in Patients While Reading and Using Visual Display Terminals. International journal

    Tsugiaki Utsunomiya, Atsushi Kawahara, Kazuomi Hanada, Akitoshi Yoshida

    Cornea   36 ( 8 )   908 - 914   2017.8

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    PURPOSE: Diquafosol ophthalmic solution improves objective findings in the ocular surface and subjective symptoms in patients with dry eye. The Dry Eye-Related Quality-of-Life Score (DEQS) questionnaire was developed to assess dry eye symptoms and their effects on quality of life. However, because little research using the DEQS has been reported, we evaluated the effects of diquafosol ophthalmic solution on ocular surface findings and quality of life using the DEQS in patients with dry eye. METHODS: Sixty-three patients with dry eye were assigned to the control group (artificial tears) or diquafosol group. Both groups instilled 1 drop of the solution in both eyes 6 times daily and were evaluated after 2 weeks; the diquafosol group also was instructed to be examined at 1 and 3 months. We evaluated the subjective symptoms using the DEQS, fluorescein staining score, tear film breakup time (BUT), Schirmer testing, and lower tear meniscus height with anterior-segment optical coherence tomography. RESULTS: In the diquafosol group, the fluorescein staining score, BUT, tear meniscus height, and DEQS scores improved significantly compared with before treatment in contrast to the control group. Furthermore, in the diquafosol group, the staining score and BUT improved significantly compared with the control group. Analysis of each DEQS item indicated that diquafosol ophthalmic solution relieved foreign body sensation and problems when reading and using visual display terminals compared with the control group. CONCLUSIONS: Diquafosol ophthalmic solution was effective in patients with dry eye, especially those with foreign body sensation and problems when reading and using visual display terminals.

    DOI: 10.1097/ICO.0000000000001241

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  • [Amniotic Membrane Transplantation for Corneal and Conjunctival Diseases: Classification of Application and Outcomes from Analysis of 95 cases].

    Kazuomi Hanada, Noriko Nishikawa, Nobuhito Ishii, Tsugiaki Utsunomiya, Akitoshi Yoshida

    Nippon Ganka Gakkai zasshi   121 ( 4 )   359 - 5   2017.4

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    Purpose: To evaluate the indications and outcomes of amniotic membrane (AM) transplantation for corneal and conjunctival diseases. Subjects and methods: Ninety-five eyes of ninety patients who underwent AM transplantation between January 2007 and May 2016 were included in this study. The surgical procedures, diagnosis and postoperative outcomes were investigated retrospectively. Results: Transplantation was conducted in three surgical procedures. AM patch, for the promotion of corneal re-epithelialization, was performed in 14 cases with persistent epithelial defects. Thirteen cases healed with total epithelialization. Corneal perforation was noted in Stevens-Johnson syndrome and cured with keratoplasty. AM graft for basement membrane supply, was performed in 72 cases. Of these, 32 cases had been followed for at least one year after AM graft out of which pterygium recurred at one year in 5. Conjunctival tumor recurred in 3 out of 17 cases, and was treated with a repeated of AM graft. AM stuff for substrate supply to the deep corneal layer, was performed in 9 cases with corneal perforation. Leakage of aqueous humor was cured in all 9 cases. Seven cases had keratoplasty performed after the AM stuff and recovered completely. The other 2 cases were observed without additional surgery. There were no complications due to the AM transplantation during the course of treatment in any of the 95 cases. Conclusion: AM transplantation is applied in three different procedures. Each of these was effective in achieving the corneal and conjunctival reconstruction designed for it.

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  • Transforming Growth Factor-β Signaling Cascade Induced by Mechanical Stimulation of Fluid Shear Stress in Cultured Corneal Epithelial Cells. International journal

    Tsugiaki Utsunomiya, Akihiro Ishibazawa, Taiji Nagaoka, Kazuomi Hanada, Harumasa Yokota, Nobuhito Ishii, Akitoshi Yoshida

    Investigative ophthalmology & visual science   57 ( 14 )   6382 - 6388   2016.11

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    PURPOSE: Because blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells, we investigated the effects of fluid shear stress on cultured human corneal epithelial cells (HCECs). METHODS: The HCECs were exposed to shear stress (0, 1.2, 12 dyne/cm2) with the parallel-plate type of flow chamber. Wound healing, cellular proliferation, growth factor expression, TGF-β1 concentration in the culture supernatant, and phosphorylation of SMAD2 were investigated. RESULTS: Monolayers of HCECs exposed to shear stress had delayed wound healing and decreased proliferation compared with those of the static control (0 dyne/cm2). With increasing shear stress, TGF-β1 expression and phosphorylation of SMAD2 increased significantly, but the levels of total TGF-β1 in the culture supernatant decreased significantly. Delayed wound healing, decreased proliferation, and phosphorylation of the SMAD2 by shear stress were canceled out with a TGF-β receptor inhibitor. CONCLUSIONS: Fluid shear stress on the HCECs affected TGF-β signaling, which was associated with delayed wound healing. Mechanical stress by blinking might involve TGF-β signaling, and activation of TGF-β might be a key factor in wound healing of the corneal epithelium. Further studies should investigate the molecular mechanism of shear stress-induced activation of TGF-β.

    DOI: 10.1167/iovs.16-20638

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  • Transforming Growth Factor-β Signaling Cascade Induced by Mechanical Stimulation of Fluid Shear Stress in Cultured Corneal Epithelial Cells. Reviewed

    Utsunomiya T, Ishibazawa A, Nagaoka T, Hanada K, Yokota H, Ishii N, Yoshida A.

    Investigative Ophthalmology Visual Science   2016

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  • Comparison of effect of nepafenac and diclofenac ophthalmic solutions on cornea, tear film, and ocular surface after cataract surgery: the results of a randomized trial. International journal

    Atsushi Kawahara, Tsugiaki Utsunomiya, Yuji Kato, Yoshinori Takayanagi

    Clinical ophthalmology (Auckland, N.Z.)   10   385 - 91   2016

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    BACKGROUND: The aim of this study was to compare the effects of nepafenac ophthalmic suspension 0.1% (Nevanac) and diclofenac sodium ophthalmic solution 0.1% (Diclod) on the cornea, tear film, and ocular surface after cataract surgery. METHODS: A total of 60 eyes (60 patients) were selected for this study, with no ocular diseases other than cataract (scheduled for cataract surgery by one surgeon). Patients were randomly enrolled to receive nepafenac or diclofenac in the perioperative period, and cataract surgery was performed using torsional microcoaxial phacoemulsification and aspiration with intraocular lens implantation via a transconjunctival single-plane sclerocorneal incision at the 12 o'clock position. We compared intra- and intergroup differences preoperatively and postoperatively in conjunctival and corneal fluorescein staining scores, tear film breakup times, Schirmer's tests, the Dry Eye Related Quality of Life Scores, and tear meniscus areas using anterior segment optical coherence tomography. RESULTS: The diclofenac group had significantly higher conjunctival and corneal fluorescein staining scores at 4 weeks postoperatively compared with the nepafenac group (P<0.001). Within the diclofenac group, significantly higher conjunctival and corneal fluorescein staining scores were noted at 4 weeks postoperatively than those seen preoperatively (P<0.001) and at 1 week postoperatively (P<0.001). No statistically significant differences were found in any other items. CONCLUSIONS: Nepafenac ophthalmic suspension 0.1% is considered safe for the corneal epithelium after cataract surgery.

    DOI: 10.2147/OPTH.S101836

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  • Imaging of the Corneal Sub-Basal Whorl-Like Nerve Plexus: More Accurate Depiction of the Extent of Corneal Nerve Damage in Patients with Diabetes. Invited Reviewed

    Utsunomiya T, Nagaoka T, Hanada K, Omae T, Yokota H, Abiko A, Haneda M, Yoshida A.

    Investigative Ophthalmology Visual Science   2015.9

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  • Imaging of the Corneal Subbasal Whorl-like Nerve Plexus: More Accurate Depiction of the Extent of Corneal Nerve Damage in Patients With Diabetes. International journal

    Tsugiaki Utsunomiya, Taiji Nagaoka, Kazuomi Hanada, Tsuneaki Omae, Harumasa Yokota, Atsuko Abiko, Masakazu Haneda, Akitoshi Yoshida

    Investigative ophthalmology & visual science   56 ( 9 )   5417 - 23   2015.8

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    PURPOSE: To show that noninvasive in vivo corneal confocal microscopy (IVCM) can make more accurate imaging of the corneal subbasal nerve plexus possible. This diagnostic technique monitors the status of diabetic peripheral neuropathy. However, it is difficult to accurately confirm the corneal area captured by IVCM, which can induce measurement errors. Because the whorl-like characteristic pattern of the corneal subbasal nerve plexus is in the inferocentral cornea, we evaluated whether IVCM images of the whorl-like patterns can accurately evaluate the corneal nerve fibers in diabetic neuropathy. METHODS: Forty-seven patients with diabetes (DM group) and 21 healthy control subjects underwent IVCM examination to compare the characteristics of the corneal subbasal nerve plexus around the central cornea (conventional method) and the whorl-like pattern in the inferocentral cornea (study method). We measured the total corneal nerve fiber and branch length (CNFL). RESULTS: The total CNFL were significantly shorter in the DM group than in the control group and tended to decrease with progression of diabetic retinopathy, nephropathy, neuropathy, and decreased corneal sensation. There was a significant positive correlation between the CNFL values obtained with the conventional method and those obtained with the study method. The coefficient of variation of the CNFL values in the study method was significantly smaller than in the conventional method. CONCLUSIONS: Our findings indicated that IVCM measurements of the whorl-like patterns may accurately define the extent of corneal nerve damage in order to monitor diabetic peripheral neuropathy.

    DOI: 10.1167/iovs.15-16609

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  • Wound healing process after corneal stromal thinning observed with anterior segment optical coherence tomography. Reviewed

    Utsunomiya T, Hanada K, Muramatsu O, Ishibazawa A, Nishikawa N, Yoshida A.

    Cornea   2014.10

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  • Wound healing process after corneal stromal thinning observed with anterior segment optical coherence tomography. International journal

    Tsugiaki Utsunomiya, Kazuomi Hanada, Osamu Muramatsu, Akihiro Ishibazawa, Noriko Nishikawa, Akitoshi Yoshida

    Cornea   33 ( 10 )   1056 - 60   2014.10

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    PURPOSE: The aim of this study was to observe the wound healing process after corneal stromal thinning by using anterior segment optical coherence tomography (AS-OCT) and a slit lamp. METHODS: Four patients with corneal stromal thinning (2 patients: corneal iron foreign bodies; 2 patients: keratitis) were included. Serial AS-OCT and slit-lamp examinations were used to follow up the progress of these patients. The thicknesses of the whole cornea and the corneal stroma were measured with AS-OCT and compared with the findings observed during the slit-lamp examination. RESULTS: AS-OCT showed that epithelial hypertrophy and hyperplasia initially occurred in the area of the corneal stromal thinning; subsequently, scar tissue formed in the area with an improvement in the thickness of the corneal stroma. This wound healing process was observed in all 4 patients. The scar tissue initially appeared opaque on slit-lamp examination and was characterized by a high signal produced on AS-OCT, which was different from the normal corneal stroma. The scar tissue gradually appeared clear on slit-lamp examination; however, the high signal on AS-OCT remained. CONCLUSIONS: AS-OCT can be used to detect the wound healing process of corneal stromal thinning.

    DOI: 10.1097/ICO.0000000000000223

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Books

  • ドライアイと涙道疾患ナビゲート

    堀裕一他( Role: Joint author涙液検査)

    中山書店  2024.3 

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    Language:Japanese   Book type:Scholarly book

  • 角膜上皮びらんと遷延性角膜上皮欠損

    宇都宮嗣了( Role: Sole author)

    全日本病院出版会  2020.3 

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  • 生体共焦点顕微鏡角膜モジュールを用いた、糖尿病患者における角膜神経叢の神経密度解析

    宇都宮 嗣了, 長岡 泰司( Role: Joint author)

    医学出版  2016 

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MISC

  • 線維柱帯切開術眼内法における切開範囲の術後眼圧への影響

    大坪 充, 善岡 尊文, 木ノ内 玲子, 川井 基史, 中林 征吾, 神谷 隆行, 宇都宮 嗣了, 宋 勇錫

    臨床眼科   77 ( 10 )   1314 - 1319   2023.10

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    <文献概要>目的:線維柱帯切開術眼内法における切開範囲の術後成績への影響を検討した。対象と方法:旭川医科大学病院および市立稚内病院において2017年3月~2021年9月にマイクロフックトラベクロトミー,スーチャートラベクロトミー眼内法を施行し6ヵ月間通院した62例74眼を対象とし,術前眼圧,術後6ヵ月の眼圧を後ろ向きに検討を行った。結果:平均年齢71.5±12.1歳,切開範囲202.4±85.4度,病型は広義原発開放隅角緑内障44眼,落屑緑内障11眼,ぶどう膜炎続発緑内障7眼,ステロイド緑内障12眼であった。全体で術前平均眼圧は21.2±9.5mmHg,術後6ヵ月後眼圧は14.5±6.0mmHgであり,有意に下降した(p<0.0001)。術後眼圧を目的変数として多変量解析を行ったが,切開範囲との関連はなかった(p=0.38)。術後眼圧下降率を目的変数として同様の解析を行うと,切開範囲で有意な相関があった[回帰係数(95%信頼区間),0.07(0~0.13);p<0.05]。結論:本研究で線維柱帯切開範囲による術後眼圧への影響はみられなかった。しかし,切開範囲は眼圧下効率の増加に関与する可能性が示唆された。

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01537&link_issn=&doc_id=20230927080019&doc_link_id=10.11477%2Fmf.1410214938&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410214938&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 【薬疹】COVID-19に対するワクチン(BNT162b2)接種後に生じたStevens-Johnson症候群の1例

    小林 友紀, 菅野 恭子, 松本 洸, 梅影 香央里, 高橋 千晶, 藤井 瑞恵, 宇都宮 嗣了, 岸部 麻里, 山本 明美

    皮膚科の臨床   65 ( 10 )   1463 - 1466   2023.9

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    <文献概要>88歳,男性。初回のCOVID-19ワクチン(BNT162b2)接種後,口腔内びらんが出現し,2回目の接種翌日より口腔内びらんの悪化,結膜充血がみられた。その10日後,両上肢に紅斑が出現したため当科を受診した。初診時,両上肢,手背,前胸部に一部痂皮を伴う鮮紅色紅斑を認めた。口唇,口腔内のびらんと結膜充血を認め,Stevens-Johnson症候群と診断した。プレドニゾロン1mg/kg/日投与で皮疹および粘膜症状は改善した。自験例では眼合併症との関連が指摘されているHLA-A*02:06が検出された。自験例は他剤の内服歴はなく,COVID-19ワクチンが発症に関与したと考えた。ワクチンの普及で今後,同様の報告の増加が見込まれ,本邦でも症例を集積し検討すべきと考える。

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01266&link_issn=&doc_id=20230925080008&doc_link_id=10.18888%2Fhi.0000004138&url=https%3A%2F%2Fdoi.org%2F10.18888%2Fhi.0000004138&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 線維柱帯切開術眼内法における切開範囲の術後眼圧への影響

    大坪 充, 善岡 尊文, 木ノ内 玲子, 中林 征吾, 神谷 隆行, 宇都宮 嗣了, 宋 勇錫, 川井 基史

    日本眼科学会雑誌   127 ( 臨増 )   218 - 218   2023.3

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  • 新型コロナウイルスワクチンによるStevens-Johnson症候群の1例

    小林 友紀, 菅野 恭子, 松本 洸, 梅影 香央里, 高橋 千晶, 大坪 紗和, 岸部 麻里, 山本 明美, 藤井 瑞恵, 宇都宮 嗣了

    日本皮膚科学会雑誌   132 ( 12 )   2699 - 2699   2022.11

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  • 【眼科鑑別診断の勘どころ】角膜上皮びらんと遷延性角膜上皮欠損

    宇都宮 嗣了

    OCULISTA   ( 84 )   33 - 41   2020.3

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    角膜上皮は眼表面の重要なバリア機能を担っており、それらの恒常性を維持するため、角膜上皮は丈夫でかつ高い創傷治癒能力を有している。角膜上皮障害の遷延は創傷治癒能力などの破綻もしくは創傷治癒能力を凌駕する障害が眼表面に起こっているということを意味し、大変由々しき状況である。角膜上皮障害は、表層上皮のみの障害である点状表層角膜上皮症(SPK)、上皮全層の欠損である角膜上皮びらん、上皮欠損が遷延した遷延性角膜上皮欠損(PED)、実質損傷を伴う角膜潰瘍、に分類される。角膜上皮びらんと遷延性角膜上皮欠損の鑑別には上皮欠損部の形が重要であり、角膜上皮びらんでは上皮欠損部は内に凸になることが多いのに対し、遷延性角膜上皮欠損では類円形の上皮欠損となることが多い。類円形の角膜上皮欠損を診察した場合、角膜上皮の創傷治癒が遅延していることが多く、注意が必要である。(著者抄録)

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  • 旭川医科大学病院眼科における眼表面扁平上皮新生物(OSSN)の検討

    花田 一臣, 廣川 博之, 武井 英博, 西川 典子, 石居 信人, 宇都宮 嗣了, 横山 一弘, 吉田 晃敏

    臨床眼科   73 ( 5 )   603 - 609   2019.5

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    <文献概要>目的:眼表面扁平上皮新生物(OSSN)について病理組織学的診断と臨床的傾向を検討する。対象と方法:2005年6月~2018年5月の間に旭川医科大学病院眼科で加療したOSSN 16名18眼。性別,発症時年齢,発生部位,病理組織学的診断,治療,経過を後ろ向きに調査した。結果:性別は男性14名16眼,女性2名2眼,発症時年齢は平均62.0±20.5歳(30~96歳),病理組織学的診断は角結膜上皮内新生物(CIN)15眼,扁平上皮癌(SCC)3眼であった。発生部位は角膜輪部9眼,球結膜2眼,円蓋部結膜5眼,瞼結膜2眼であった。初回術式は13眼(CIN 12眼,SCC 1眼)に腫瘍全切除と羊膜移植,CIN 3眼に腫瘍全切除,SCC 2眼に部分切除生検が行われ,術後療法は6眼(CIN 5眼,SCC 1眼)にマイトマイシンC点眼,CIN 4眼にインターフェロン点眼,SCC 3眼に放射線照射が行われた。CIN 6眼には術後療法が行われなかった。再発は3眼(17%)で,CIN 2眼に再切除と羊膜移植,SCC 1眼に放射線再照射が行われた。合併症は2眼に瞼球癒着,1眼に角膜輪部疲弊が生じた。結論:OSSNは男性に多く,発生部位は角膜輪部と球結膜にCINが多く,円蓋部結膜と瞼結膜にSCCがみられた。腫瘍切除と羊膜移植の組み合わせと術後治療の工夫で,腫瘍再発防止と良好な眼表面再建を得た。

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J01537&link_issn=&doc_id=20190507100015&doc_link_id=10.11477%2Fmf.1410213141&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410213141&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

  • 角結膜の再建に羊膜移植を施行した95眼 用途の分類と効果の検討

    花田 一臣, 西川 典子, 石居 信人, 宇都宮 嗣了, 吉田 晃敏

    日本眼科学会雑誌   121 ( 4 )   359 - 365   2017.4

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    目的:角結膜の再建に対する羊膜移植の用途と効果を明らかにする.対象と方法:2007年1月から2016年5月までの9年5ヵ月間に羊膜移植を施行した90名95眼について,用途,疾患の内訳,経過を後ろ向きに検討した.結果:実施された羊膜移植は用途別に3つに分類できた.上皮再生保護を目的とした羊膜パッチは遷延性上皮欠損14眼に施行され,13眼で上皮欠損が消失し,Stevens-Johnson症候群の1眼で穿孔を生じ角膜移植を施行した.角結膜の基底膜供給を目的とした羊膜グラフトは72眼に施行され,翼状片切除後1年以上観察できた32眼中5眼に再発がみられた.腫瘍切除後の17眼中3眼に再発を生じ羊膜移植の再施行で対応した.より深層への基質供給を目的とした羊膜スタッフは角膜穿孔9眼に施行され,全例に房水漏出停止を得た.術後7眼に角膜移植が施行され,残りの2眼はそのまま経過した.95眼全例で羊膜移植に関する合併症を認めなかった.結論:羊膜移植は3つの用途に分類され,それぞれ角結膜の再建に有効である.(著者抄録)

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    Other Link: https://search.jamas.or.jp/default/link?pub_year=2017&ichushi_jid=J01049&link_issn=&doc_id=20170419550002&doc_link_id=%2Fdz1nigan%2F2017%2F012104%2F001%2F0359-0365%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdz1nigan%2F2017%2F012104%2F001%2F0359-0365%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

  • 流れ負荷装置を用いたメカニカルストレスが及ぼすヒト培養角膜上皮細胞への影響の解明

    宇都宮 嗣了

    旭川医科大学研究フォーラム   17   54 - 55   2017.3

  • 【糖尿病神経障害の早期診断と薬物療法】糖尿病神経障害の早期診断に役立つ検査 生体共焦点顕微鏡角膜モジュールを用いた、糖尿病患者における角膜神経叢の神経密度解析

    宇都宮 嗣了, 長岡 泰司

    月刊糖尿病   8 ( 8 )   49 - 53   2016.8

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  • 流体力学的アプローチによる瞬目時摩擦刺激に対する角膜上皮細胞の応答 MMP

    宇都宮 嗣了, 石羽澤 明弘, 長岡 泰司, 花田 一臣, 吉田 晃敏

    日本眼科学会雑誌   120 ( 臨増 )   230 - 230   2016.3

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  • 生体共焦点顕微鏡角膜モジュールによる糖尿病患者の角膜上皮下神経密度の測定

    宇都宮 嗣了, 長岡 泰司, 花田 一臣, 横田 陽匡, 吉田 晃敏

    日本眼科学会雑誌   118 ( 臨増 )   311 - 311   2014.3

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  • 網膜の微細な形態・機能解析への挑戦とその輝かしい未来

    吉田 晃敏, 長岡 泰司, 石子 智士, 高橋 淳士, 佐藤 栄一, 大前 恒明, 中林 征吾, 石羽澤 明弘, 横田 陽匡, 十川 健司, 谷 智文, 棚野 一郎, 籠川 浩幸, 木ノ内 玲子, 花田 一臣, 高宮 央, 川井 基史, 村松 治, 山口 亨, 西川 典子, 亀山 大希, 伊藤 はる奈, 大野 晋治, 石田 美織, 坪井 尚子, 善岡 尊文, 神谷 隆行, 高橋 賢伍, 宇都宮 嗣了, 林 弘樹, 守屋 潔, 三上 大季, 廣川 博之, 安藤 譲二, 山本 希美子, 神谷 暸, Kuo Lih, Feke Gilbert T., Van de Velde Frans

    日本眼科学会雑誌   117 ( 3 )   212 - 245   2013.3

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    1.網膜の微細形態解析への挑戦 我々は長年,網膜の微細形態解析を目的に,走査レーザー検眼鏡(scanning laser ophthalmoscope:SLO)の開発にかかわってきた.特に我々が最近開発に携わった国産初のSLOには,「側方絞り」を搭載し,この絞りで撮影する方法を「レトロモード」と名付けた.これを用いることで,黄斑浮腫における【嚢】胞様変化や網膜上膜下の網膜皺襞などを明瞭に観察することが可能となった.特発性黄斑円孔に関する微細形態解析を,スペクトラルドメイン光干渉断層計(spectral-domain optical coherence tomography:SD-OCT)を用いて行い,黄斑円孔形成過程の初期病変を検討した.中心窩点状黄色病変であるステージ1-A切迫黄斑円孔は,SD-OCT所見では,中心窩網膜に癒着する硝子体の前方牽引により視細胞外節末端ラインが引き上げられた三角形の中心窩網膜【剥】離であることが判明した.さらに,全層黄斑円孔における黄斑部硝子体界面について検討した.細隙灯顕微鏡検査で完全後部硝子体【剥】離(posterior vitreous detachment:PVD)のない全層黄斑円孔例に対し,SD-OCT検査を行うと,黄斑部硝子体界面に4つの形態が認められ,ステージ2・3全層黄斑円孔の約92%は,傍中心窩後部硝子体【剥】離(perifoveal PVD)による硝子体の前方牽引で発症し,また,約55%には,中心窩網膜に開いたルーフ状の内層網膜を認め,網膜組織の欠損と考えられる蓋(true operculum)が形成される危険性があると考えられた.2.網膜の機能解析への挑戦 一方,網膜の機能を評価するため,SLOを用いて視機能評価を行った.独自に開発した微小視野検査のプログラムを用いて網膜感度と局所視力を定量的に評価し,黄斑疾患患者における偏心視域の特徴とその評価の重要性を明らかにした.SLOは,網膜の微細形態を観察しながら網膜機能を評価できる装置であり,我々は,治療までをも1つの装置で行えるall in oneの新たな装置開発への挑戦を続けている.また我々は,非侵襲的かつ定量的な眼循環測定法であるレーザードップラー眼底血流計を開発し,これを用いて,基礎から臨床にまたがる眼循環のトランスレーショナルリサーチを行った.臨床研究では,網膜血流の自己調節機構のメカニズムを解明するとともに,2型糖尿病患者では網膜症発症前および発症早期に網膜血流量が低下することを明らかにした.ネコを用いたin vivo実験系では生理的負荷時における網膜循環調節のメカニズムを詳細に解明し,血管内皮がその調節に重要な役割を果たすことを明らかにした.また我々は,in vitroの実験系で,シェアストレスによる培養ヒト網膜血管内皮細胞の遺伝子発現変化を検討し,網膜細動脈レベルの生理的なシェアストレスを長時間負荷すると,網膜血管内皮細胞は内皮型一酸化窒素合成酵素やトロンボモジュリンの遺伝子発現を増加させ,一方でエンドセリン-1の遺伝子発現を減少させることを明らかにした.さらに,我々は,ex vivo摘出血管実験系を用いて,シンバスタチン,ピオグリタゾン,レスベラトロール,フェノフィブラートなどが網膜血管を用量依存性に拡張させることを明らかにし,これらの薬剤が2型糖尿病患者などの低下した網膜血流を改善させる可能性があることを明らかにした.3.切れ目のない医学・医療支援体制の確立 患者の微細網膜画像をリアルタイムに送受信することで,大学病院から関連病院眼科を支援できるシステムを構築した.立体ハイビジョン画像伝送システムの開発を行い,眼科領域に最適な立体表示方法を確立し,効率的かつ高画質な伝送方式を確立した.Peer to Peer技術を用いた医療情報共有システムや,災害時に緊急性や重要性の高い情報を優先的に伝送できるネットワーク制御技術も開発した.我が国と同様に,都市部と地方の医療格差問題を抱える中国政府からの要請で,これらの技術を北京市や上海市を含む4地域の病院に提供した.また,遠隔在宅医療支援システムを独自に開発し,自宅療養中の退院患者を病院からフォローアップすることを可能とした.すなわち,我々は,網膜の形態・機能解析の結果を世界中の人々と共有できる仕組みを完成した.4.眼底からの全身健康管理 我々は,網膜の微細な形態・機能解析に,装置の開発も含めて長年挑戦し,多くの成果を挙げてきた.網膜には,全身の情報が存在するので,眼科医が網膜の微細形態・機能解析を同時に行い,それらの結果を我々が開発した遠隔医療の手法を用いることで,世界中の人々と共有できることを示した.眼科医が,人々の「眼底からの全身健康管理」に貢献できることは,我々眼科医の誇りであり,我々の輝かしい未来はここにあると信じている.(著者抄録)

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Research Projects

  • 眼表面摩擦関連疾患における角膜上皮細胞アンギオポエチン様蛋白4の役割解明

    Grant number:19K18865  2019.4 - 2025.3

    日本学術振興会  科学研究費助成事業  若手研究

    宇都宮 嗣了

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    Grant amount:\4,160,000 ( Direct Cost: \3,200,000 、 Indirect Cost:\960,000 )

    涙腺摘出や乾燥環境負荷などin vivoのドライアイモデルは多く存在するが、それらのモデルでは摩擦だけでなく炎症や浸透圧亢進など様々な要因が加わってし まい、実験結果の解釈を複雑にしてしまう。in vitroの実験モデルではそれらの因子は排除出来るが、定量的な実験を行うには特殊な実験系の構築が必要であ る。我々は平行平板型流れ負荷装置を用いた水流シェアストレスによって培養細胞に定量的に長時間にわたって機械的刺激を負荷する実験系を確立しており、こ の手法を培養ヒト角膜上皮細胞に応用し、瞬目の摩擦による角膜上皮への慢性的な機械的刺激を再現した。 網羅的遺伝子解析を行ったところ、シェアストレス を負荷した角膜上皮細胞では様々な遺伝子発現が変化していたが、ANGPTL4(アンギオポエチン様蛋白4)の遺伝子発現が圧倒的に上昇していた。シェアストレスを 負荷した角膜上皮細胞ではWBにてANGPTL4蛋白も増加することがわかった。また、マウス角膜の免疫染色において 角膜上皮にはANGPTL4が高発現していることも わかった。現在のところ実際の生体角膜におけるANGPTL4の役割は不明であるが、マウス角膜の免疫染色においても 角膜上皮にANGPTL4が高発現していることか ら、ANGPTL4は角膜上皮において何らかの機能を持っている蛋白であることが示唆される。閉鎖された乾燥環境でマウスに送風することで、マウスにドライアイ環境を負荷するドライアイアイモデルを作成し、ANGPTL4の発現の変化を解析中である。また、眼瞼に粘性物質を塗布することで不快感から目を掻痒することに よる、掻痒シェアストレス負荷モデルも作成し、現在解析中である。
    また、シェアストレスを負荷した角膜上皮細胞ではMMPの発現が変化することが確認出来たため、それらの内容を学会発表し、学術論文として投稿し、Experimental Eye Research誌に掲載された。

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  • Signaling induced by mechanical stimulation of fluied shear stress in cultured corneal epithelial cells

    Grant number:16K20295  2016.4 - 2019.3

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Young Scientists (B)

    Utsunomiya Tsugiaki, Nagaoka Taiji, Hanada Kazuomi, Ishii Nobuhito, Ishibazawa Akihiro, Matsumoto Chiemi

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    Grant amount:\3,900,000 ( Direct Cost: \3,000,000 、 Indirect Cost:\900,000 )

    Because blinking is regarded as mechanical stimulation of fluid shear stress on the corneal epithelial cells, we investigated the effects of fluid shear stress on cultured human corneal epithelial cells (HCECs). The HCECs were exposed to shear stress with the parallel-plate type of flow chamber, which exposed the cells to variable levels of laminar shear stress.
    Fluid shear stress on the HCECs affected TGF-β signaling, which was associated with delayed wound healing. Mechanical stress by blinking might involve TGF-β signaling, and activation of TGF-β might be a key factor in wound healing of the corneal epithelium. Further studies should investigate the molecular mechanism induced shear stress.

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