2025/10/24 更新

写真a

スズムラ アヤナ
鈴村 文那
SUZUMURA Ayana
所属
医学部附属病院 眼科 病院助教
職名
病院助教

学位 1

  1. 博士(医学) ( 2020年4月   名古屋大学 ) 

研究分野 1

  1. ライフサイエンス / 眼科学

受賞 2

  1. 福田賞

    2021年10月   日本糖尿病眼学会  

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    受賞区分:国内学会・会議・シンポジウム等の賞 

  2. CIBoGリトリート 医学奨励賞

    2021年2月   名古屋大学・大学院医学系研究科  リトリート事務局  

 

論文 33

  1. 増刊号 眼科診療のピットフォールあるある-対応スキル爆上げのヒント 6.網膜血管障害 糖尿病患者の診察③-原点回帰! 押さえておきたい鑑別診断と確認すべき全身性リスク因子

    鈴村 文那

    臨床眼科   79 巻 ( 11 ) 頁: 177 - 183   2025年10月

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    出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.037055790790110177

    CiNii Research

  2. Application of Metagenomic Long-Read Sequencing for the Diagnosis of Herpetic Uveitis Open Access

    Koyanagi, Y; Sajiki, A; Yuki, K; Ushida, H; Kawano, K; Fujita, K; Shimizu, H; Okuda, D; Kosaka, M; Yamada, K; Suzumura, A; Kachi, S; Kaneko, H; Komatsu, H; Usui, Y; Goto, H; Nishiguchi, KM

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   66 巻 ( 4 ) 頁: 50   2025年4月

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    記述言語:英語   出版者・発行元:Investigative Ophthalmology and Visual Science  

    PURPOSE. To investigate the sensitivity and specificity of herpes virus detection by nanopore metagenomic analysis (NMA) compared with multiplex polymerase chain reaction (mPCR)-positive and -negative controls. METHODS. This study included 43 patients with uveitis who had been screened for intraocular herpes virus infection using mPCR from aqueous humor samples. Aqueous humor samples stored after mPCR were subjected to whole-genome amplification, long-read sequencing, and analysis of the phylogenetic microorganism composition using a Flongle flow cell on the Oxford Nanopore MinION platform. For samples that tested positive with mPCR and negative with the Flongle flow cell, additional long-read sequencing was performed using a MinION flow cell, which enabled acquisition of more sequence data. The sensitivity and specificity of herpes virus detection by NMA were compared with the mPCR-positive and -negative controls. RESULTS. NMA using a Flongle flow cell detected the pathogenic virus in 60.0% of those who tested positive by mPCR (12/20). Further analysis using the MinION flow cell successfully identified viral DNA fragments in three out of the eight initially undetected samples, yielding a collective sensitivity of 75.0% (15/20). All of the virus detected with the long-read sequencing were identical to those diagnosed by mPCR testing, and none of the samples that tested negative by mPCR revealed herpes viral DNA with the use of long-read sequencing. CONCLUSIONS. For the detection of etiologic herpes virus DNA fragments, NMA revealed a reasonable sensitivity and high specificity. Our study highlights the potential of nanopore sequencing to facilitate further advances in uveitis diagnosis.

    DOI: 10.1167/iovs.66.4.50

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  3. Silicone oil, an intraocular surgical adjuvant, induces retinal ferroptosis 国際誌

    Shimizu, H; Tanaka, H; Tazaki, A; Yamada, K; Suzumura, A; Ota, J; Ushio-Watanabe, N; Zheng, H; Kataoka, K; Hara, H; Nishikawa, Y; Yasukawa, T; Suzuma, K; Terasaki, H; Nishiguchi, KM; Kato, M; Toyokuni, S; Kaneko, H

    FREE RADICAL BIOLOGY AND MEDICINE   228 巻   頁: 33 - 43   2025年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Free Radical Biology and Medicine  

    Vitrectomy with silicone oil (SO) endotamponade is an effective treatment for vision-threatening retinal diseases. However, unexplained vision impairment has been reportedly critical side effects. Previously, we reported that the eyes with ocular toxoplasmosis showed retinal ferroptosis with the clinical sign of reduced intravitreal iron (Fe). We also found that total iron levels in sub-silicone oil fluid (SOF) in eyes with SO endotamponade were significantly reduced. We hypothesized that the cause of complications related to SO endotamponade is retinal ferroptosis and that low total iron in SOF is a secondary change that occurs similarly to the changes in ocular toxoplasmosis. In this study, we measured total iron levels in ocular fluid from patients, rabbits with SO endotamponade. Retinal iron taken up from the SOF was evaluated using laser ablation inductively coupled plasma mass spectrometry in human and rabbit eyes. Retinal ferroptosis was confirmed by immunohistochemistry of 4-hydrox-2-nonenal-modified proteins, FeRhoNox-1 staining, western blotting and RT-PCR. We found low total iron levels in the SOF, increased oxidative stress and Fe uptake from the SOF into the retinae of human and rabbit eyes, as well as decreased GPx4 expression, increased FeRhoNox-1 signals and altered Fe-related gene expression in SO-filled rabbit eyes. Of note, the target of ferroptosis was Müller cells. We generated an in vitro silicone oil-filled eye model using MIO-M1 cells (a human Müller cell line). The in vitro SO-filled eye model showed decreased GPx4 expression and increased intracellular catalytic Fe(II), an increase in ferroptosis, prevention of cell death by ferrostatin-1, a ferroptosis inhibitor, and altered Fe-related gene expression. These results indicate that the cause of complications related to SO endotamponade was the induction of retinal (Müller cell) ferroptosis, which can be prevented by ferrostatin-1.

    DOI: 10.1016/j.freeradbiomed.2024.12.039

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  4. Enhanced Monofocal IOLs Improve Patient Satisfaction in Phaco-Vitrectomy for ERM

    Ota, J; Matsunaga, M; Haga, F; Suzumura, A; Yamada, K; Shimizu, H; Kachi, S; Ota, I; Miyake, G; Mokuno, K; Inooka, D; Iwata, E; Akahori, T; Nishiguchi, KM; Kaneko, H

    CLINICAL OPHTHALMOLOGY   19 巻   頁: 3283 - 3293   2025年

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  5. Assessment of factors affecting anterior chamber depth from data obtained from health checkup participants in Japan Open Access

    Inooka, T; Kominami, T; Tomita, R; Suzumura, A; Matsuno, T; Ota, J; Koyanagi, Y; Takeyama, H; Ueno, S; Ito, Y; Nishiguchi, KM; Yuki, K

    SCIENTIFIC REPORTS   14 巻 ( 1 ) 頁: 30342   2024年12月

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    記述言語:英語   出版者・発行元:Scientific Reports  

    Measurement of anterior chamber depth (ACD), an important marker for the screening of primary angle-closure glaucoma, requires biometry, which is not readily used. This study assessed the relationship between ACD and health check-up data findings from participants with good corrected visual acuity in Japan. Participants underwent ophthalmic, anthropometric, and hematological assessments. The mean ACD of all 3060 participants was 3.33 ± 0.34 mm [2.22–4.72 mm]. Multivariable linear regression analysis was performed to determine factors that were significantly correlated with ACD, and logistic regression analysis was performed to predict ACD < 2.70 mm. Multivariable linear regression analysis showed that age, sex, intraocular pressure, spherical equivalent refractive error (SER), height, and fasting blood sugar levels significantly correlated with ACD (P < 0.05). Logistic regression analysis showed that age, sex, and SER were the best predictors of ACD < 2.70 mm. The area under receiving operator characteristic curves of ‘age and SER’ and ‘age, SER, and sex’ were 0.821 and 0.835, respectively, with no significant difference (P = 0.122). In conclusion, ACD correlates with several parameters, and age and SER may be particularly important for predicting ACD in participants undergoing health checkups.

    DOI: 10.1038/s41598-024-82096-1

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  6. 特集 第77回日本臨床眼科学会講演集[4] 原著 HLA-A26陽性ベーチェット病との鑑別に苦慮した真菌性眼内炎の1例

    新美 渚, 井岡 大河, 鈴村 文那, 牛田 宏昭, 西口 康二

    臨床眼科   78 巻 ( 6 ) 頁: 716 - 721   2024年6月

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    出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.1410215196

    CiNii Research

  7. Decrease in electrolyte after vitrectomy surgery may affect the results of forensic investigations using vitreous humor Open Access

    Ushida, H; Suzumura, A; Yamada, K; Shimizu, H; Suzuki, A; Ishikawa, Y; Kikuchi, R; Nishiguchi, KM; Kaneko, H

    BMC OPHTHALMOLOGY   24 巻 ( 1 ) 頁: 219   2024年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Ophthalmology  

    Purpose: Vitreous humor (VH) is used for postmortem biochemical studies because it is well protected in an uncontaminated state even after death. The goal of this research was to investigate electrolyte concentrations in the VH from human eyes with and without a history of vitrectomy surgery. Methods: We analyzed the sodium (Na), potassium (K), chloride (Cl) and magnesium (Mg) concentrations from 34 VH samples from 34 patients. Eleven samples were from eyes with a history of vitrectomy, and the remaining 23 eyes had no history of vitrectomy. The correlations of Na, K, Cl and Mg concentrations with patient age, interval between first and second vitrectomy, and lens status (history of cataract surgery) were also evaluated. Results: The Na, K, Cl and Mg concentrations in VH from vitrectomized eyes were 134.1 ± 7.9 mmol/L, 3.7 ± 0.2 mmol/L, 99.7 ± 6.7 mmol/L and 0.59 ± 0.09 mmol/L, respectively; all were significantly lower than the corresponding concentrations in VH from control eyes (lower by 5.0%, 11.0%, 11.7%, and 22.6%, respectively). Na, K, Cl and Mg concentrations in VH from vitrectomized eyes did not show significant correlations with patient ages or the interval between their first and second vitrectomies. There were no significant differences in Na, K, Cl and Mg concentrations in VH between phakic eyes and intraocular lens-implanted eyes. Conclusions: With the increasing number of vitrectomies being performed, it is necessary to consider the history of vitrectomy when using a subject’s VH in forensic examination.

    DOI: 10.1186/s12886-024-03445-2

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    その他リンク: https://link.springer.com/article/10.1186/s12886-024-03445-2/fulltext.html

  8. 特集 第77回日本臨床眼科学会講演集[2] 原著 病初期より視神経炎を認めた再発性多発軟骨炎の1例

    牛田 知子, 牛田 宏昭, 夏目 啓吾, 鈴村 文那, 西口 康二

    臨床眼科   78 巻 ( 4 ) 頁: 505 - 510   2024年4月

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    出版者・発行元:株式会社医学書院  

    DOI: 10.11477/mf.1410215151

    CiNii Research

  9. Retinal ferroptosis as a critical mechanism for the induction of retinochoroiditis during ocular toxoplasmosis 国際誌 Open Access

    Yamada, K; Tazaki, A; Ushio-Watanabe, N; Usui, Y; Takeda, A; Matsunaga, M; Suzumura, A; Shimizu, H; Zheng, H; Ariefta, NR; Yamamoto, M; Hara, H; Goto, H; Sonoda, KH; Nishiguchi, KM; Kato, M; Nishikawa, Y; Toyokuni, S; Kaneko, H

    REDOX BIOLOGY   67 巻   頁: 102890 - 102890   2023年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Redox Biology  

    Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer <sup>57</sup>Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.

    DOI: 10.1016/j.redox.2023.102890

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  10. Association Between Torque Teno Virus and Systemic Immunodeficiency in Patients With Uveitis With a Suspected Infectious Etiology 査読有り 国際誌

    Sajiki, A; Koyanagi, Y; Ushida, H; Kawano, K; Fujita, K; Okuda, D; Kawabe, M; Yamada, K; Suzumura, A; Kachi, S; Kaneko, H; Komatsu, H; Usui, Y; Goto, H; Nishiguchi, KM

    AMERICAN JOURNAL OF OPHTHALMOLOGY   254 巻   頁: 80 - 86   2023年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:American Journal of Ophthalmology  

    PURPOSE: To determine the correlation between the presence of torque teno virus (TTV) in the aqueous humor of patients with uveitis and clinical information, including immunodeficiency history. DESIGN: Multicenter, retrospective, cross-sectional study. METHODS: Fifty-eight patients with uveitis with a suspected infectious etiology and 24 controls with cataract or age-related macular degeneration were included. We used quantitative polymerase chain reaction to test all subjects for TTV and multiplex polymerase chain reaction to test uveitis subjects for common ocular pathogens. When possible, both serum and aqueous humor samples were tested. Ocular TTV positivity was compared with age, sex, and a history of systemic immunodeficiency with logistic analysis. RESULTS: Ocular TTV positivity was found in 23%, 11%, and 0% of patients with herpetic uveitis, nonherpetic uveitis, and controls, respectively. Among patients with herpes infection, positivity for ocular TTV was found in 43%, 8%, 14%, and 50% of patients with cytomegalovirus retinitis, iridocyclitis, acute retinal necrosis, and Epstein–Barr virus–positive uveitis, respectively. Patients with cytomegalovirus retinitis showed a significantly higher rate of ocular TTV infection than controls (P =.008). Serum analysis revealed TTV positivity in 90% of patients with uveitis and in 100% of controls. Age- and gender-adjusted logistic analysis revealed a correlation between ocular TTV positivity and systemic immunodeficiency (P =.01), but no correlations between ocular TTV and age, gender, or viral pathogenic type. CONCLUSIONS: These findings suggest that positivity for ocular TTV was correlated with a clinical history of systemic immunodeficiency.

    DOI: 10.1016/j.ajo.2023.06.012

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  11. 眼科診断・治療のイノベーション ゲノム医療による眼疾患の診断・治療のイノベーション

    西口 康二, 藤田 幸輔, 小柳 俊人, 佐治木 愛, 川野 健一, 山田 和久, 川部 満希, 奥田 大志, 鈴村 文那, 清水 英幸, 牛田 宏昭, 兼子 裕規, 小松 紘之, 臼井 嘉彦, 後藤 浩, 中澤 徹, 加地 秀

    日本眼科学会雑誌   127 巻 ( 3 ) 頁: 402 - 422   2023年3月

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    記述言語:日本語   出版者・発行元:(公財)日本眼科学会  

  12. Dimethyl Fumarate Protects Retinal Pigment Epithelium from Blue Light-Induced Oxidative Damage via the Nrf2 Pathway Open Access

    Shimizu, H; Takayama, K; Yamada, K; Suzumura, A; Sato, T; Nishio, Y; Ito, M; Ushida, H; Nishiguchi, KM; Takeuchi, M; Kaneko, H

    ANTIOXIDANTS   12 巻 ( 1 )   2023年1月

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    記述言語:英語   出版者・発行元:Antioxidants  

    The purpose of this study is to investigate the protective effect of dimethyl fumarate (DMF), the methyl-ester of fumaric acid, against blue-light (BL) exposure in retinal pigment epithelial (RPE) cells. ARPE-19 cells, a human RPE cell line, were cultured with DMF followed by exposure to BL. Reactive oxygen species (ROS) generation, cell viability, and cell death rate were determined. Real-time polymerase chain reaction and Western blotting were performed to determine the change in nuclear factor (erythroid-derived)-like 2 (NRF2) expression. Twenty-seven inflammatory cytokines in the supernatant of culture medium were measured. BL exposure induced ROS generation in ARPE-19 cells, which DMF alleviated in a concentration-dependent manner. BL exposure increased the ARPE-19 cell death rate, which DMF alleviated. BL exposure induced ARPE-19 cell apoptosis, again alleviated by DMF. Under BL exposure, DMF increased the NRF2 mRNA level and promoted NRF2 expression in the nucleus. BL also strongly increased interleukin (IL)-1β and fibroblast growth factor (FGF) expression. BL strongly induced RPE cell damage with apoptotic change while DMF mainly reduced inflammation in BL-induced RPE damage, resulting in blockade of cell death. DMF has a protective effect in RPE cells against BL exposure via activation of the NRF2 pathway.

    DOI: 10.3390/antiox12010045

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  13. Oxidative Stress-Induced Cellular Senescence in Aging Retina and Age-Related Macular Degeneration Open Access

    Terao, R; Ahmed, T; Suzumura, A; Terasaki, H

    ANTIOXIDANTS   11 巻 ( 11 )   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Antioxidants  

    Aging leads to a gradual decline of function in multiple organs. Cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) are age-related ocular diseases. Because their pathogenesis is unclear, it is challenging to combat age-related diseases. Cellular senescence is a cellular response characterized by cell cycle arrest. Cellular senescence is an important contributor to aging and age-related diseases through the alteration of cellular function and the secretion of senescence-associated secretory phenotypes. As a driver of stress-induced premature senescence, oxidative stress triggers cellular senescence and age-related diseases by inducing senescence markers via reactive oxygen species and mitochondrial dysfunction. In this review, we focused on the mechanism of oxidative stress-induced senescence in retinal cells and its role in the pathogenesis of AMD.

    DOI: 10.3390/antiox11112189

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  14. Interleukin-19 ameliorates experimental autoimmune encephalitis

    Takeuchi H., Horiuchi H., Parajuli B., Komiya H., Tanaka F., Suzumura A.

    Clinical and Experimental Neuroimmunology   12 巻 ( 3 ) 頁: 148 - 149   2021年8月

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    出版者・発行元:Clinical and Experimental Neuroimmunology  

    DOI: 10.1111/cen3.12642

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  15. Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases 国際誌

    Suzumura, A; Terao, R; Kaneko, H

    ANTIOXIDANTS   9 巻 ( 10 ) 頁: 1 - 25   2020年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Antioxidants  

    Oxidative stress and inflammation play crucial roles in the development and progression of retinal diseases. Retinal damage by various etiologies can result in retinopathy of prematurity (ROP), diabetic retinopathy (DR), and age-related macular degeneration (AMD). n-3 fatty acids are essential fatty acids and are necessary for homeostasis. They are important retinal membrane components and are involved in energy storage. n-3 fatty acids also have antioxidant and anti-inflammatory properties, and their suppressive effects against ROP, DR, and AMD have been previously evaluated. α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and their metabolites have been shown to alleviate retinal oxidative stress and inflammation involving various biological signaling pathways. In this review, we summarize the current understanding of the n-3 fatty acids effects on the mechanisms of these retinal diseases and how they exert their therapeutic effects, focusing on ALA, EPA, DHA, and their metabolites. This knowledge may provide new remedial strategies for n-3 fatty acids in the prevention and treatment of retinal diseases associated with oxidative stress and inflammation.

    DOI: 10.3390/antiox9100920

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  16. Caveolin-1 Promotes Cellular Senescence in Exchange for Blocking Subretinal Fibrosis in Age-Related Macular Degeneration 国際誌 Open Access

    Shimizu, H; Yamada, K; Suzumura, A; Kataoka, K; Takayama, K; Sugimoto, M; Terasaki, H; Kaneko, H

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   61 巻 ( 11 ) 頁: 21 - 21   2020年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Investigative Ophthalmology and Visual Science  

    PURPOSE. To determine whether caveolin-1 (i) prevents epithelial-mesenchymal transition in the RPE and laser-induced subretinal fibrosis and (ii) promotes or inhibits cellular senescence in the RPE. METHODS. We examined laser-induced subretinal fibrosis and RPE cell contraction in wild-type and Caveolin-1 knockout (Cav-1<sup>-/-</sup>) mice treated with or without cavtratin, a cell-permeable peptide of caveolin-1. The senescence marker p16<sup>INK4a</sup>was measured in RPE tissues from patients with geographic atrophy and aged mice, laser-induced subretinal fibrosis, and primary human RPE cells. Human RPE was examined by TUNEL staining, reactive oxygen species generation, cell viability, and senescence-associated β-galactosidase staining. RESULTS. The volume of subretinal fibrosis was significantly smaller in cavtratin-injected eyes from wild-type mice than in control eyes from wild-type, P = 0.0062, and Cav-1<sup>-/-</sup>mice, P = 0.0095. Cavtratin treatment produced significant improvements in primary RPE cell contraction in wild-type, P = 0.04, and Cav-1<sup>-/-</sup>mice, P = 0.01. p16<sup>INK4a</sup>expression in the RPE was higher in patients with than without geographic atrophy. p16<sup>INK4a</sup>was expressed in 18-month-old but not 2-month-old wild-type mouse eyes. p16<sup>INK4a</sup>and collagen type I antibodies showed co-localization in subretinal fibrosis. Cavtratin did not affect RPE cell apoptosis or reactive oxygen species generation, but decreased cell viability and increased senescence-associated β-galactosidase-positive cells. CONCLUSIONS. Enhanced expression of caveolin-1 successfully blocked epithelial- mesenchymal transition of RPE and the reduction of subretinal fibrosis in mice. Nevertheless, in exchange for blocking subretinal fibrosis, caveolin-1 promotes RPE cellular senescence and might affect the progression of geographic atrophy in AMD.

    DOI: 10.1167/iovs.61.11.21

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  17. Lamivudine Inhibits <i>Alu</i> RNA-induced Retinal Pigment Epithelium Degeneration via Anti-inflammatory and Anti-senescence Activities 国際誌

    Yamada Kazuhisa, Kaneko Hiroki, Shimizu Hideyuki, Suzumura Ayana, Namba Rina, Takayama Kei, Ito Seina, Sugimoto Masataka, Terasaki Hiroko

    TRANSLATIONAL VISION SCIENCE & TECHNOLOGY   9 巻 ( 8 ) 頁: 1 - 1   2020年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Translational Vision Science and Technology  

    Purpose: Accumulation of the long noncoding Alu element RNA activates the NLRP3 inflammasome and leads to retinal pigment epithelium (RPE) cell death, a key event in the pathogenesis of geographic atrophy during late-stage age-related macular degeneration. Lamivudine (3TC) is a nucleoside analog reverse transcriptase inhibitor known to inhibit the NLRP3 inflammasome. Currently, the intracellular response of the senescence marker p16Ink4a to the long noncoding RNA is being actively studied. The present study aimed to assess the efficacy of 3TC against Alu RNA-induced RPE inflammation and senescence by evaluating changes in expression of the proinflammatory cytokines IL-18 and IL-1β and of p16INK4a in RPE cells. Methods: Cultured human RPE cells and in vivo mouse RPE cells were transfected with an in vitro-transcribed Alu RNA, and changes in IL-18, IL-1β, and p16Ink4a expression measured in the presences of 3TC or 3,4-(M)CA as a negative control. Results: Treatment with 3TC markedly reduced Alu RNA-induced expression of IL-18 and IL-1β in human and mouse RPE cells compared with the negative control. Further, Alu RNA-induced p16INK4a expression was suppressed by 3TC in human RPE cells. Conclusions: Our data suggest that Alu RNA accumulation contributes to RPE cell senescence in age-related macular degeneration and that this pathogenic process can be suppressed by 3TC. Translational Relevance: Further verifying this study leads to potential targets for agerelated macular degeneration therapy.

    DOI: 10.1167/tvst.9.8.1

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  18. n-3 Fatty Acid and Its Metabolite 18-HEPE Ameliorate Retinal Neuronal Cell Dysfunction by Enhancing Muller BDNF in Diabetic Retinopathy 国際誌 Open Access

    Suzumura, A; Kaneko, H; Funahashi, Y; Takayama, K; Nagaya, M; Ito, S; Okuno, T; Hirakata, T; Nonobe, N; Kataoka, K; Shimizu, H; Namba, R; Yamada, K; Ye, FX; Ozawa, Y; Yokomizo, T; Terasaki, H

    DIABETES   69 巻 ( 4 ) 頁: 724 - 735   2020年4月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Diabetes  

    Diabetic retinopathy (DR) is a widespread vision-threatening disease, and neuroretinal abnormality should be considered as an important problem. Brain-derived neurotrophic factor (BDNF) has recently been considered as a possible treatment to prevent DR-induced neuroretinal damage, but how BDNF is upregulated in DR remains unclear. We found an increase in hydrogen peroxide (H<inf>2</inf>O<inf>2</inf>) in the vitreous of patients with DR. We confirmed that human retinal endothelial cells secreted H<inf>2</inf>O<inf>2</inf> by high glucose, and H<inf>2</inf>O<inf>2</inf> reduced cell viability of MIO-M1, Müller glia cell line, PC12D, and the neuronal cell line and lowered BDNF expression in MIO-M1, whereas BDNF administration recovered PC12D cell viability. Streptozocin-induced diabetic rats showed reduced BDNF, which is mainly expressed in the Müller glia cell. Oral intake of eicosapentaenoic acid ethyl ester (EPA-E) ameliorated BDNF reduction and oscillatory potentials (OPs) in electroretinography (ERG) in DR. Mass spectrometry revealed an increase in several EPA metabolites in the eyes of EPA-E–fed rats. In particular, an EPA metabolite, 18-hydroxyeicosapentaenoic acid (18-HEPE), induced BDNF upregulation in Müller glia cells and recovery of OPs in ERG. Our results indicated diabetes-induced oxidative stress attenuates neuroretinal function, but oral EPA-E intake prevents retinal neurodegeneration via BDNF in Müller glia cells by increasing 18-HEPE in the early stages of DR.

    DOI: 10.2337/db19-0550

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  19. Diacron reactive oxygen metabolites and biological antioxidant potential tests for patients with age-related macular degeneration 国際誌 Open Access

    Matsuura, T; Kaneko, H; Takayama, K; Shibata, R; Kataoka, K; Ito, S; Tsunekawa, T; Shimizu, H; Suzumura, A; Namba, R; Ito, Y; Murohara, T; Terasaki, H

    BMC OPHTHALMOLOGY   20 巻 ( 1 ) 頁: 56 - 56   2020年2月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BMC Ophthalmology  

    Background: Previously, we showed that serum malondialdehyde (MDA) was significantly higher in patients with neovascular age-related macular degeneration (nAMD) than in those without AMD. The Diacron reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) tests are known markers of oxidative stress. The aim of this study was to use d-ROMs and BAP tests to evaluate changes in systemic oxidative stress in patients with nAMD. Methods: Blood serum samples were collected from 34 patients with nAMD (mean age: 76.5 ± 7.7 years; 22 men) and 20 control subjects (mean age: 62.9 ± 14.0 years; 10 men), and d-ROMs and BAP tests were examined. Results: In men, the mean level of d-ROMs for the nAMD patients was significantly higher than that for the controls (312.0 ± 52.4 vs. 275.1 ± 45.5 U.CARR, respectively; P <.05). There was a significant correlation between d-ROM level and CNV lesion area in the male nAMD group (r =.42, P =.05). There were no significant differences in mean BAP test results between the nAMD patients and controls for either sex (men: 2241 ± 549 vs. 2136 ± 246 μmol/L; women: 2263 ± 292 vs. 2335 ± 161 μmol/L). Conclusion: The d-ROMs test may provide a useful indicator of nAMD in men but not in women.

    DOI: 10.1186/s12886-020-01334-y

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  20. Silicone oil-associated retinal light exposure under a surgical microscope 国際誌 Open Access

    Yamada, K; Kaneko, H; Tsunekawa, T; Shimizu, H; Suzumura, A; Namba, R; Takeuchi, J; Kataoka, K; Takayama, K; Inoue, M; Ito, Y; Terasaki, H

    ACTA OPHTHALMOLOGICA   97 巻 ( 5 ) 頁: E742 - E746   2019年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Acta Ophthalmologica  

    Purpose: Based on the hypothesis that silicone oil (SO) with a higher refractive index than water induces unexpected vignetting effects during surgeries, we aimed to investigate the relationship between the volume of SO and light intensity using a surgical microscope. Methods: Using a light-sensitive paper and model eye filled with varying volumes (0%, 50%, 62.5%, 75%, 87.5% and 100%) of SO, the light intensity of intraocular lens (IOL) with various refractive powers (0, 10 and 20 dioptres) illuminated by a surgical microscope was measured. Results: Light exposure density with 1.0% coaxial and oblique light was approximately 22-fold higher than that with 0.1% coaxial and oblique light. Further, it was approximately 34-fold higher in eyes with +20 D IOL than in those with no IOL. The density in eyes with 75% SO was the highest among all groups followed by that with 0% SO. Light exposure densities in the eyes with 75% and 0% SO were significantly higher than those with other volumes of SO. In SO-filled eyes, a microscope set with only an oblique light and a filter successfully reduced light exposure. Conclusion: Silicone oil-related vision loss (SORVL) during SO removal surgeries might be due to increased light exposure on the macular retina caused by the SO-associated vignetting effect. SORVL could be prevented by placing a filter in the microscope during SO removal surgeries.

    DOI: 10.1111/aos.14038

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  21. Possible mechanism of silicone-oil related vision loss in intractable retinal diseases

    Kaneko, H; Shimizu, H; Yamada, K; Suzumura, A; Namba, R; Terasaki, H

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   60 巻 ( 9 )   2019年7月

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  22. In Vitro Epiretinal Membrane Model and Antibody Permeability: Relationship With Anti-VEGF Resistance in Diabetic Macular Edema 国際誌 Open Access

    Namba, R; Kaneko, H; Suzumura, A; Shimizu, H; Kataoka, K; Takayama, K; Yamada, K; Funahashi, Y; Ito, S; Nonobe, N; Terasaki, H

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   60 巻 ( 8 ) 頁: 2942 - 2949   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Investigative Ophthalmology and Visual Science  

    PURPOSE. Diabetic macular edema (DME) is characterized by an accumulation of fluid in the macula due to diabetic retinopathy. Currently, anti-VEGF drugs are the standard treatment worldwide for DME. This study aimed to assess whether the existence of epiretinal membrane (ERM) affects anti-VEGF efficacy, due to reduced permeability of the antibody through the ERM. METHODS. We retrospectively examined clinical data of DME patients who underwent anti- VEGF treatment and evaluated whether clinical differences existed between DME eyes with ERM and those without ERM. We then created an in vitro ERM model using MIO-M1, ARPE-19, and NTI-4 cells on Transwell membranes and evaluated antibody permeability through this in vitro ERM model using fluorescently labeled antibodies. RESULTS. Central retinal thickness (CRT) change between before and 1 month after first anti- VEGF treatment, as well as final CRT and final visual acuity 12 months after first anti-VEGF treatment, significantly differed between DME eyes with ERM and those without ERM. The in vitro ERM model led to production of collagen I in a manner similar to that of human ERM specimens. Fluorescence intensity of the lower chamber of the in vitro ERM model was significantly reduced in a dose-dependent manner. CONCLUSIONS. Clinical data analysis indicated that the existence of ERM in DME eyes lowered the efficacy of anti-VEGF treatment. Reduced antibody permeability through the in vitro ERM model suggested ERM presence was associated with resistance to anti-VEGF treatment in DME eyes with ERM.

    DOI: 10.1167/iovs.19-26788

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  23. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE FOVEAL AVASCULAR ZONE IN CHILDREN WITH A HISTORY OF TREATMENT-REQUIRING RETINOPATHY OF PREMATURITY 国際誌

    Nonobe, N; Kaneko, H; Ito, Y; Takayama, K; Kataoka, K; Tsunekawa, T; Matsuura, T; Suzumura, A; Shimizu, H; Terasaki, H

    RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES   39 巻 ( 1 ) 頁: 111 - 117   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Retina  

    Purpose:To examine the characteristics of the foveal vascular structure of patients with retinopathy of prematurity (ROP) by optical coherence tomography angiography.Methods:Ten patients with a history of laser photocoagulation or cryopexy treatment for Stage 3 (Zone ≥ II) ROP and 10 normal subjects (controls) were included. Foveal avascular zone, vessel density, vessel length, and vascular diameter index were measured by optical coherence tomography angiography using the 3 × 3-mm Early Treatment Diabetic Retinopathy Study (ETDRS) sectors.Results:The median foveal avascular zone values of the patients with ROP and controls were 0.103 mm<sup>2</sup> and 0.260 mm<sup>2</sup>, respectively (P = 0.0025). The medians of the vessel density, vessel length, and vascular diameter index of the patients with ROP were 0.218 mm<sup>2</sup>/mm<sup>2</sup>, 11.75 mm/mm<sup>2</sup>, and 18.00 m, respectively, in ETDRS Sector 1 and did not significantly differ from those of the controls (P = 0.940, 0.733, and 0.705, respectively). For the average of ETDRS Sectors 2 to 5, the medians of the vessel density, vessel length, and vascular diameter index for the patients with ROP were 0.347 mm<sup>2</sup>/mm<sup>2</sup>, 18.95 mm/mm<sup>2</sup>, and 18.28 m, respectively; vessel density and vessel length were significantly smaller than those of the controls (P = 0.002 and 0.003, respectively), but there was no significant difference in vascular diameter index (P = 0.286).Conclusion:Optical coherence tomography angiography-guided foveal avascular zone was significantly smaller in patients with ROP than in controls. Our results indicate that foveal vascular development may be altered in patients with a history of treatment-requiring ROP.

    DOI: 10.1097/IAE.0000000000001937

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  24. Biological Characteristics of Subsilicone Oil Fluid and Differences With Other Ocular Humors 国際誌 Open Access

    Shimizu, H; Kaneko, H; Suzumura, A; Takayama, K; Namba, R; Funahashi, Y; Kataoka, K; Iwase, T; Hwang, SJ; Ito, S; Yamada, K; Ueno, S; Ito, Y; Terasaki, H

    TRANSLATIONAL VISION SCIENCE & TECHNOLOGY   8 巻 ( 1 ) 頁: 28 - 28   2019年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Translational Vision Science and Technology  

    Purpose: Subsilicone oil fluid (SOF) in eyes with silicone oil (SO) endotamponade possibly has a role in complications (e.g., vision loss); thus, we aimed to examine inflammatory cytokine and electrolyte levels and retinal glial cell viability in SOF. Methods: We measured major inflammatory cytokine levels and electrolytes in SOF and compared them with those in vitreous fluid (VF) and anterior chamber fluid (ACF). We analyzed the correlation between inflammatory cytokines and retinal thickness in SO-filled eyes. Further, we measured the MIO-M1 cell viability in medium with SOF and compared it with that containing VF. Results: We collected and examined 57 SOF, 22 ACF, and 21 VF samples from eyes with PVR, PDR, RD, and MH. Interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 levels in SOF were significantly higher than those in ACF. There was no significant difference for all cytokines between SOF and VF. Retinal thickness changes during SO endotamponade were not correlated with the presence of any inflammatory cytokines. Levels of ferrous iron, but not of potassium, showed a significant decrease in SOF compared with VF. The WST-1 assay showed that SOF-added medium induced higher MIO-M1 cell viability than VF-added medium. Conclusions: We found no significant correlation between the change in the retinal thickness and cytokine levels, but SOF contains higher concentrations of cytokines and lower concentrations of ferrous iron and can be biologically distinguished from ACF and VF. Translational Relevance: Novel knowledge of inflammatory cytokine levels and electrolytes in SOF provides better understanding of pathology of SO-filled eyes.

    DOI: 10.1167/tvst.8.1.28

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  25. Novel Classification of Early-stage Systemic Hypertensive Changes in Human Retina Based on OCTA Measurement of Choriocapillaris 国際誌 Open Access

    Takayama, K; Kaneko, H; Ito, Y; Kataoka, K; Iwase, T; Yasuma, T; Matsuura, T; Tsunekawa, T; Shimizu, H; Suzumura, A; Ra, E; Akahori, T; Terasaki, H

    SCIENTIFIC REPORTS   8 巻 ( 1 ) 頁: 15163 - 15163   2018年10月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    The traditional classification of hypertensive retinopathy was based on the Keith–Wagener–Barker (KWB) grading, which is a subjective scaling system, and it is difficult to distinguish between the first and second grades. Retinal and choroidal vasculatures are affected by systemic hypertension, although retinal vasculature changes with age, axial length, intraocular pressure, and retinal diseases. It is necessary to establish a new objective method to assess hypertensive vascular changes. In the present study, we have examined the vasculature of the macular choriocapillaris in order to establish a new objective method to assess hypertensive vascular changes using optical coherence tomography angiography (OCTA). Choriocapillaris vessel density (VD), vessel length, and vessel diameter index in a 3 × 3 mm macular area were measured by OTCA in a total of 567 volunteers (361 healthy subjects and 206 subjects with systemic hypertension) who attended a basic health check-up. Ocular factors, systemic factors, and medications were evaluated. We detected significant differences in normative choriocapillaris vasculature between the left and right eyes in 53 healthy subjects and revealed correlations between age, intraocular pressure, axial length, and choriocapillaris vasculature in 308 healthy subjects. Normative foveal VD was correlated with age only and the efficiency was weak. The analysis of 206 right eyes (KWB grade 0, 159 eyes; grade 1, 35 eyes; and grade 2, 12 eyes) revealed that foveal VD was strongly correlated with KWB grade only (P < 0.001). This is the first report suggesting that OCTA for foveal choriocapillaris measurement by OCTA would might provide the advantage of evaluating be objective method for evaluating the progression of systemic hypertension.

    DOI: 10.1038/s41598-018-33580-y

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  26. The role of brain-derived neurotrophic factor on retinal dysfunction in diabetic retinopathy and its association with eicosapentaenoic acid

    Namba, R; Kaneko, H; Kataoka, K; Tsunekawa, T; Matsuura, T; Suzumura, A; Shimizu, H; Terasaki, H

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   59 巻 ( 9 )   2018年7月

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  27. The relationship between inflammatory cytokines in the sub-silicone oil fluid and retinal thickness in eyes with proliferative vitreoretinopathy and proliferative diabetic retinopathy.

    Kaneko, H; Shimizu, H; Tsunekawa, T; Iwase, T; Matsuura, T; Suzumura, A; Namba, R; Terasaki, H

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   59 巻 ( 9 )   2018年7月

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  28. Optical coherence tomography angiography of choriocapillaris: normative macular choriocapillaris vasculature and novel classification of early-stage systemic hypertensive changes: A cross-sectional study

    Takayama, K; Ito, Y; Kaneko, H; Kataoka, K; Iwase, T; Tsunekawa, T; Shimizu, H; Suzumura, A; Akahori, T; Terasaki, H

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   59 巻 ( 9 )   2018年7月

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  29. Diacron-reactive oxygen metabolites and biological antioxidant potential tests in patients with age-related macular degeneration

    Matsuura, T; Kaneko, H; Takayama, K; Shimizu, H; Tsunekawa, T; Suzumura, A; Namba, R; Terasaki, H

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   59 巻 ( 9 )   2018年7月

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  30. Clinical advantage of Swept-Source Optical Coherence Tomography for the patients with retinal hemorrhage due to retinal microaneurysms: a case series

    Shimizu, H; Kaneko, H; Tsunekawa, T; Matsuura, T; Suzumura, A; Terasaki, H

    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE   59 巻 ( 9 )   2018年7月

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  31. Cytokine profiling in the sub-silicone oil fluid after vitrectomy surgeries for refractory retinal diseases 国際誌 Open Access

    Kaneko, H; Takayama, K; Asami, T; Ito, Y; Tsunekawa, T; Iwase, T; Funahashi, Y; Ueno, S; Nonobe, N; Yasuda, S; Suzumura, A; Shimizu, H; Kimoto, R; Hwang, SJ; Terasaki, H

    SCIENTIFIC REPORTS   7 巻 ( 1 ) 頁: 2640 - 2640   2017年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Scientific Reports  

    Silicone oil (SO) is an intraocular surgical adjuvant that reduces the surgical complications in refractory retinal diseases, although membrane and cellular proliferation is often seen even in SO-filled eyes. We hypothesised that the fluid in the space between the SO and the retina, named the "sub-silicone oil fluid (SOF)", enhances these biological responses. We proposed a safe method for SOF extraction. We also analysed inflammatory cytokine expressions and SOF osmotic pressures from eyes with rhegmatogenous retinal detachment (RRD), proliferative diabetic retinopathy (PDR), proliferative vitreoretinopathy (PVR) and macular hole-associated retinal detachment (MHRD). Interleukin (IL)-10, IL-12p40, IL-6, monocyte chemotactic protein-1, and vascular endothelial growth factor (VEGF) in the SOF with PVR were significantly higher than in those with RRD or MHRD. Fibroblast growth factor-2, IL-10, IL-12p40, IL-8, VEGF, and transforming growth factor beta 1 levels in eyes with exacerbated PDR indicated a significantly higher expression than those with simple PDR. IL-6 and tumour necrosis factor alpha in eyes with exacerbated PVR demonstrated a significantly higher expression than in those with simple PVR. However, there was no difference in SOF osmotic pressure between group of each disease. These studies indicate that disease-specific SOF is a significant reflection of disease status.

    DOI: 10.1038/s41598-017-03124-x

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  32. Better Visual Outcome by Intraocular Lens Ejection in Geriatric Patients with Ruptured Ocular Injuries 国際誌 Open Access

    Kaneko, H; Asami, T; Sugita, T; Tsunekawa, T; Matsuura, T; Takayama, K; Yamamoto, K; Kachi, S; Ito, Y; Ueno, S; Nonobe, N; Kataoka, K; Suzumura, A; Iwase, T; Terasaki, H

    PLOS ONE   12 巻 ( 1 ) 頁: e0170094   2017年1月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Plos One  

    Ocular trauma is one of the leading causes of visual impairment worldwide. Because of the popularity of cataract surgeries, aged individuals with ocular trauma commonly have a surgical wound in their eyes. The purpose of this study was to evaluate the visual outcome of cases that were coincident with intraocular lens (IOL) ejection in the eyes with ruptured open-globe ocular injuries. Consecutive patients with open-globe ocular injuries were first reviewed. Patients' characteristics, corrected distance visual acuities (CDVAs) over 3 years after the trauma, causes of injuries, traumatic wound patterns, and coexistence of retinal detachment were examined. The relationships between poor CDVA and the other factors, including the complications of crystalline lens and IOL ejection, were examined. A total of 105 eyes/patients [43 eyes with rupture, 33 with penetrating, 28 with intraocular foreign body (IOFB), and 1 with perforating injuries] were included. Rupture injuries were common in aged patients and were mostly caused by falls, whereas penetrating and IOFB injuries were common in young male patients. CDVAs of the eyes with rupture injuries were significantly worse than those of the eyes with penetrating or IOFB injuries. CDVA from more than 50% of the ruptured eyes resulted in no light perception or light perception to 20/500. CDVA of the ruptured eyes complicated by crystalline lens ejection was significantly worse than that of those complicated by IOL ejection. The wounds of the ruptured eyes complicated by IOL ejection were mainly located at the superior corneoscleral limbus, whereas those of the eyes complicated by crystalline lens ejection were located at the posterior sclera. There were significant correlations between poor CDVA and retinal detachment and crystalline lens ejection. These results proposed a new trend in the ocular injuries that commonly occur in aged patients; history of cataract surgery might affect the final visual outcome after open-globe ocular injuries.

    DOI: 10.1371/journal.pone.0170094

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  33. Correlation between miR-148 Expression in Vitreous and Severity of Rhegmatogenous Retinal Detachment 国際誌 Open Access

    Tsunekawa, T; Kaneko, H; Takayama, K; Hwang, SJ; Oishi, A; Nagasaka, Y; Ye, FX; Iwase, T; Nonobe, N; Ueno, S; Ito, Y; Yasuda, S; Matsuura, T; Shimizu, H; Suzumura, A; Kataoka, K; Terasaki, H

    BIOMED RESEARCH INTERNATIONAL   2017 巻   頁: 3427319 - 3427319   2017年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Biomed Research International  

    Purpose. We had earlier reported positive hsa-miR-148a-3p expression in eyes with rhegmatogenous retinal detachment (RRD) and its involvement in the epithelial-mesenchymal transition of retinal pigment epithelium in vitro. Here we investigated the association of hsa-miR-148a-3p expression levels in the vitreous fluid of patients with RRD with severity of RRD. Methods. The hsa-miR-148a-3p expression levels in the vitreous fluid, range (degree) of retinal detachment (RD), and pixels of retinal break were measured in 27 eyes with RRD. The association of hsa-miR-148a-3p expression levels with other factors was evaluated by multiple regression analysis. Results. The hsa-miR-148a-3p expression levels, time from onset of RRD to vitrectomy, range of RD, and pixels of retinal breaks were 23.68±43.00, 12.07±15.36 days, 155.85±86.67 degrees, and 37000±67100 pixels, respectively. Five eyes with RRD had vitreous hemorrhage preoperatively. The hsa-miR-148a-3p expression levels were significantly associated with pixels of retinal breaks (β=0.699) and the time from onset of RRD to vitrectomy (β=0.358) but not with the range of RD or presence of vitreous hemorrhage. Conclusion. The hsa-miR-148a-3p expression levels in the vitreous fluid were significantly associated with the size of retinal break and disease duration.

    DOI: 10.1155/2017/3427319

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▼全件表示

書籍等出版物 6

  1. 網膜電図

    鈴村文那( 担当: 単著)

    中山書店  2025年5月 

  2. 注目のイチオシ論文―やさしく解説― 第26回 8.抗セラミド抗体療法は糖尿病による網膜微小血管障害を改善する可能性がある

    鈴村文那( 担当: 単著)

    2025年5月 

  3. 糖尿病網膜症・黄斑浮腫における新規創薬治療

    鈴村文那( 担当: 単著)

    2025年3月 

  4. IOIおよび分子標的治療薬の有害事象とその対策 眼障害

    鈴村文那( 担当: 単著)

    2024年6月 

  5. 網膜疾患の過去・現在・未来 糖尿病網膜症

    鈴村文那( 担当: 単著)

    2023年12月 

  6. 基礎研究コラム71:糖尿病による網膜神経障害の抑制

    鈴村文那( 担当: 単著)

    2023年4月 

▼全件表示

MISC 2

  1. 眼炎症性疾患のロングリードシーケンスによる迅速なメタゲノム解析

    小柳 俊人, 佐治木 愛, 牛田 宏昭, 小松 紘之, 鈴村 文那, 山田 和久, 川部 満希, 川野 健一, 兼子 裕規, 臼井 嘉彦, 後藤 浩, 西口 康二  

    日本眼科学会雑誌127 巻 ( 臨増 ) 頁: 228 - 228   2023年3月

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    記述言語:日本語   出版者・発行元:(公財)日本眼科学会  

  2. 若年者にみられた両眼性の原因不明の網膜浮腫

    鈴村文那、上野真治  

    臨床眼科   2022年11月

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講演・口頭発表等 9

  1. 網膜神経保護の視点から考える糖尿病網膜症の早期治療の可能性

    鈴村文那

    第77回日本臨床眼科学会  2023年10月7日 

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    開催年月日: 2023年10月

    記述言語:日本語   会議種別:シンポジウム・ワークショップ パネル(指名)  

    開催地:東京  

  2. 家族性若年糖尿病として治療中に網膜循環障害が急速に進行した増殖糖尿病網膜症の一例

    鈴村文那

    第29回日本糖尿病眼学会  2023年6月30日 

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    開催年月日: 2023年6月 - 2023年7月

    記述言語:日本語   会議種別:ポスター発表  

  3. 糖尿病モデルマウスにおける網膜機能障害に対する老化細胞選択除去剤の効果

    第127回日本眼科学会総会 

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    開催年月日: 2023年4月

    記述言語:日本語   会議種別:口頭発表(一般)  

  4. 糖尿病モデルにおけるエイコサペンタエン酸の神経細胞保護効果の検討

    第123回日本眼科学会総会 

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    開催年月日: 2019年4月

    会議種別:口頭発表(一般)  

  5. 開放性眼外傷の分類毎の特徴と眼球破裂での有水晶体/偽水晶体脱出による術後視力の違い

    第121回日本眼科学会総会 

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    開催年月日: 2017年4月

    会議種別:ポスター発表  

  6. Neuroprotective roles of eicosapentaenoic acid and its metabolite 18-HEPE via Müller brain-derived neurotrophic factor in diabetic retinopathy 招待有り 国際会議

    2022年10月22日 

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    記述言語:英語   会議種別:シンポジウム・ワークショップ パネル(指名)  

  7. Neuroprotective roles of eicosapentaenoic acid and its metabolite 18-HEPE via Müller brain-derived neurotrophic factor in diabetic retinopathy 国際会議

    2021年11月27日 

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    記述言語:英語   会議種別:口頭発表(一般)  

  8. Neuroprotective effect of senolysis in diabetes model mouse 招待有り 国際会議

    2023年3月25日 

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    記述言語:英語   会議種別:口頭発表(一般)  

  9. The efficacy of intravitreal anti-vascular endothelial growth factor therapy on age-related macular degeneration with asteroid hyalosis 国際会議

    2017年9月8日 

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    記述言語:英語   会議種別:口頭発表(一般)  

▼全件表示

科研費 2

  1. 急性期の虚血性視神経・網膜神経障害に対するmRNA創薬への挑戦

    研究課題/研究課題番号:25K20179  2025年4月 - 2028年3月

    日本学術振興会  科学研究費助成事業  若手研究

    鈴村 文那

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    担当区分:研究代表者 

    配分額:4940000円 ( 直接経費:3800000円 、 間接経費:1140000円 )

    血流障害による急性期の視神経障害・網膜神経障害は不可逆的な視力低下を来しうるが、現時点ではこうした神経障害に対する標準的治療法は存在しない。近年、全脳虚血モデルラットに対するナノミセル型メッセンジャーRNA(mRNA)キャリアを用いた脳由来神経栄養因子(brain-derived neurotrophic factor: BDNF)mRNA投与が、神経細胞死の抑制及び記憶力の改善をもたらすことが近年明らかとなっている。本研究では血流障害による急性期の視神経障害・網膜神経障害に対するBDNF mRNA投与の治療効果を検討する。

  2. 老化細胞の選択的除去による糖尿病網膜症の予防と早期治療のための薬剤開発

    研究課題/研究課題番号:22K16949  2022年4月 - 2025年3月

    日本学術振興会  科学研究費助成事業  若手研究

    鈴村 文那

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    担当区分:研究代表者 

    配分額:4550000円 ( 直接経費:3500000円 、 間接経費:1050000円 )

    糖尿病の三大合併症の1つである糖尿病網膜症では、不可逆的な網膜内神経細胞の障害が問題となるため、早期からの神経保護治療による“予防的アプローチ”が重要である。
    近年、糖尿病により細胞老化が促進されると共に老化した細胞が糖尿病網膜症の重症化に関与する可能性や、様々なストレスを受けて不可逆的な増殖停止に至った老化細胞を薬剤によって除去できる可能性が示唆されている。
    そこで本研究では老化細胞除去薬に着目し、糖尿病網膜症に対する治療効果とそのメカニズムを検証する。
    令和4年度と同様、糖尿病モデル動物としてストレプトゾシン誘発糖尿病モデルマウスを用いて、老化マーカーであるp16INK4aを発現している細胞の局在を免疫染色で確認した。網膜神経節細胞のマーカーであるNeuN陽性細胞の一部とp16INK4a陽性細胞が共陽性であり、網膜神経節細胞の老化が疑われた。また、当初予定していた糖尿病網膜症患者の硝子体サンプルからはp16INK4aの発現が確認できなかったが、糖尿病患者のドナー眼を用いて網膜flat-mount標本における網膜神経節細胞数をカウントしたところ、対照眼と比較して減少する傾向が明らかになった。そのため、糖尿病により網膜神経節細胞が老化して、細胞障害を受ける可能性について検証していくことにした。
    一方、GLS1阻害剤を用いた追加実験での再現性を考慮し、今年度はセノリティック薬として他科でも用いられているダサチニブとケルセチンの効用を検証することにした。昨年度と同様の項目を確認したところ、ダサチニブとケルセチンの投与による体重減少や血糖上昇といった全身状態に変化はなかったが、網膜電図において糖尿病モデルマウスの律動様小波の振幅低下が有意に抑制された。また、炎症性サイトカインであるMCP-1やp16INK4aの発現も有意に改善した(いずれもp<0.05)。これらの結果は第77回臨床眼科学会のシンポジウムにて発表した。
    老化細胞の同定ならびにヒトサンプルを用いた検証を進めることができた。途中で変更した治療薬でも効果が確認できており、おおむね仮説通りの結果が得られている。
    同動物モデルマウスを用いて、網膜電図による網膜神経節細胞の機能評価を行う。また、昨年度マウス網膜から網膜神経節細胞を単離する方法を他施設にて習得した。これを用いて細胞老化と細胞障害のメカニズムの解明を進めていく。また、ヒトドナー眼の網膜切片を用いてp16INK4aの局在や発現を確認していきたい。

 

担当経験のある科目 (本学) 1

  1. 眼科

    2022