研究者詳細 - 西口　康二

Seasonal variation in submacular hemorrhages in retinal macroaneurysms and its disappearance in age-related macular degeneration 国際誌

Kaneko, H; Takashi, N; Matsunaga, M; Ito, Y; Takeuchi, J; Terasaki, H; Yatsuya, H; Nishiguchi, KM

GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY 259 巻 ( 12 ) 頁： 3589 - 3596 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Graefe's Archive for Clinical and Experimental Ophthalmology

Purpose: To investigate whether previously reported seasonal variation and winter-dominant prevalence of acute massive submacular hemorrhages (SMHs) caused by age-related macular degeneration (AMD) disappeared, and those caused by retinal microaneurysms (RMAs) emerged. Method: The medical charts of 95 patients (95 eyes) with SMH caused by AMD and 76 patients (76 eyes) with SMH caused by RMAs in 2012–2019 were retrospectively reviewed. For each subject, the month of onset, the mean ambient temperature of that month were recorded. Results: The monthly numbers of cases of SMHs caused by AMD from January to December were 6, 8, 4, 9, 7, 10, 9, 11, 7, 11, 3, and 10. No significant seasonal variation in the monthly incidence was identified (Roger’s R = 1.89, p = 0.39). The monthly numbers of SMHs caused by RMAs from January to December were 3, 11, 11, 8, 7, 8, 5, 5, 2, 4, 7, and 5. There was significant seasonal variation in the monthly incidence (Roger’s R = 7.67, p = 0.02). There was no significant correlation between the monthly incidence of SMHs caused by RMAs and mean ambient temperature. Conclusion: Our previous study conducted for cases obtained in 1998–2005 showed seasonal cyclic trend in the number of SMHs caused by AMD, with the peak in winter. However, that significant seasonal variation disappeared in 2012–2019 in the present study. Common usage of OCT devices and anti-VEGF drugs might be the reason for the lack of seasonal variation in the cases of SMH caused by AMD. [Figure not available: see fulltext.]

DOI： 10.1007/s00417-021-05280-3

CHOP deletion and anti-neuroinflammation treatment with hesperidin synergistically attenuate NMDA retinal injury in mice 国際誌

Sato, K; Sato, T; Ohno-Oishi, M; Ozawa, M; Maekawa, S; Shiga, Y; Yabana, T; Yasuda, M; Himori, N; Omodaka, K; Fujita, K; Nishiguchi, KM; Ge, S; Nakazawa, T

EXPERIMENTAL EYE RESEARCH 213 巻頁： 108826 - 108826 2021年12月

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

Glaucoma is a leading cause of blindness worldwide and is characterized by degeneration associated with the death of retinal ganglion cells (RGCs). It is believed that glaucoma is a group of heterogeneous diseases with multifactorial pathomechanisms. Here, we investigate whether anti-inflammation treatment with an ER stress blockade can selectively promote neuroprotection against NMDA injury in the RGCs. Retinal excitotoxicity was induced with an intravitreal NMDA injection. Microglial activation and neuroinflammation were evaluated with Iba1 immunostaining and cytokine gene expression. A stable HT22 cell line transfected with an NF-kB reporter was used to assess NF-kB activity after hesperidin treatment. CHOP-deficient mice were used as a model of ER stress blockade. Retinal cell death was evaluated with a TUNEL assay. As results, in the NMDA injury group, Iba1-positive microglia increased 6 h after NMDA injection. Also at 6 h, pro-inflammatory cytokines and chemokine increased, including TNFα, IL-1b, IL-6 and MCP-1. In addition, the MCP-1 promoter-driven EGFP signal, which we previously identified as a stress signal in injured RGCs, also increased; hesperidin treatment suppressed this inflammatory response and reduced stressed RGCs. In CHOP-deficient mice that received an NMDA injection, the gene expression of pro-inflammatory cytokines, chemokines, markers of active microglia, and inflammatory regulators was greater than in WT mice. In WT mice, hesperidin treatment partially prevented retinal cell death after NMDA injury; this neuroprotective effect was enhanced in CHOP-deficient mice. These findings demonstrate that ER stress blockade is not enough by itself to prevent RGC loss due to neuroinflammation in the retina, but it has a synergistic neuroprotective effect after NMDA injury when combined with an anti-inflammatory treatment based on hesperidin.

DOI： 10.1016/j.exer.2021.108826

特集網膜色素変性のアップデート【網膜色素変性:最近の話題】 SAG遺伝子変異スペクトラムとしての小口病と網膜色素変性

西口康二

臨床眼科 75 巻 ( 12 ) 頁： 1453 - 1459 2021年11月

Building Cube Method を利用した車体フレームのボクセルトポロジー最適化

和田有司, 嶋田宗将, 西口浩司, 岡澤重信, 坪倉誠

日本計算工学会論文集 2021 巻 ( 0 ) 頁： 20210019 - 20210019 2021年11月

記述言語：日本語出版者・発行元：一般社団法人日本計算工学会

大領域の金属ブロックから自動車フレームの概念構造をトポロジー最適化で得るには、1%以下の体積制約と十分な要素解像度を要する。階層直交格子を利用した有限体積法ソルバであるCUBEフレームワークを、コネクティビティつき直交格子のボクセル有限要素法ソルバとして利用することで、超並列環境でトポロジー最適化の反復解析を実行する。車体フレームを意図した数億要素のトポロジー最適化を実施し、その並列化性能を測定した。

DOI： 10.11421/jsces.2021.20210019

CiNii Research

Bilateral diffuse uveal melanocytic proliferationの1例

新田文彦, 西口康二, 國方彦志, 中澤徹

眼科臨床紀要 14 巻 ( 11 ) 頁： 771 - 772 2021年11月

Polypoidal choroidal vasculopathy in a case of retinitis pigmentosa, successfully treated with intravitreal aflibercept. 国際誌

Takahashi N, Kunikata H, Yasuda M, Hariya T, Nishiguchi KM, Nakazawa T

American journal of ophthalmology case reports 23 巻頁： 101123 - 101123 2021年9月

MRIにて発見された鉄片異物による遅発性眼内炎の1例

新田文彦, 國方彦志, 西口康二, 阿部俊明, 中澤徹

臨床眼科 75 巻 ( 7 ) 頁： 947 - 952 2021年7月

記述言語：日本語出版者・発行元：(株)医学書院

＜文献概要＞目的:金属が体内に留置されている患者にはMRIは禁忌であり,その画像の報告は稀有である。今回,MRI撮影を契機に眼内鉄片異物が発見され,眼内炎に対して硝子体手術を行った症例を経験したので報告する。症例:40歳,男性。コンクリートを鏨で叩く作業中に左眼に違和感を自覚した。受傷翌日,近医を受診したが異常は認めなかった。受傷2ヵ月後に左眼の羞明を自覚し,同近医を再診した。左眼の瞳孔散大を認め,近医神経内科へ紹介となった。MRIにて左眼とその周辺の画像が大きく変形したことから金属片の迷入が疑われ,CTにて左眼内に金属片を認めたため当院に紹介となった。所見:左眼は視力(0.8),前房と水晶体は清明,虹彩は上鼻側が一部萎縮,眼底は軽度硝子体混濁と周辺部を圧迫して観察することで12時方向の鋸状縁付近に金属片を認めた。自覚症状,他覚的所見が乏しいため経過観察としたが,受傷2ヵ月半後に眼内炎を発症したため,硝子体手術と水晶体乳化吸引術(眼内レンズは挿入せず)を施行した。硝子体の培養からはCutibacterium acnesが検出された。抗菌薬の点滴,点眼加療などを行い眼内炎は治癒した。受傷6ヵ月後に眼内レンズを挿入し,左視力(1.2)となった。結論:金属片迷入が否定できない症例へのMRIは慎重に検討し注意すべきであるが,期せずして得られたそのMRI検査では,金属による特徴的な画像を呈することがある。

その他リンク： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J01537&link_issn=&doc_id=20210628130019&doc_link_id=10.11477%2Fmf.1410214048&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1410214048&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

Regional differences in genes and variants causing retinitis pigmentosa in Japan

Koyanagi, Y; Akiyama, M; Nishiguchi, KM; Momozawa, Y; Kamatani, Y; Takata, S; Inai, C; Iwasaki, Y; Kumano, M; Murakami, Y; Komori, S; Gao, D; Kurata, K; Hosono, K; Ueno, S; Hotta, Y; Murakami, A; Terasaki, H; Wada, Y; Nakazawa, T; Ishibashi, T; Ikeda, Y; Kubo, M; Sonoda, KH

JAPANESE JOURNAL OF OPHTHALMOLOGY 65 巻 ( 3 ) 頁： 338 - 343 2021年5月

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

Purpose: To investigate the regional differences in the genes and variants causing retinitis pigmentosa (RP) in Japan Study design: Retrospective multicenter study Methods: In total, 1204 probands of each pedigree clinically diagnosed with nonsyndromic RP were enrolled from 5 Japanese facilities. The regions were divided into the Tohoku region, the Kanto and Chubu regions, and the Kyushu region according to the location of the hospitals where the participants were enrolled. We compared the proportions of the causative genes and the distributions of the pathogenic variants among these 3 regions. Results: The proportions of genetically solved cases were 29.4% in the Tohoku region (n = 500), 29.6% in the Kanto and Chubu regions (n = 196), and 29.7% in the Kyushu region (n = 508), which did not differ statistically (P =.99). No significant regional differences in the proportions of each causative gene in genetically solved patients were observed after correction by multiple testing. Among the 29 pathogenic variants detected in all 3 regions, only p.(Pro347Leu) in RHO was an autosomal dominant variant; the remaining 28 variants were found in autosomal recessive genes. Conversely, 78.6% (275/350) of the pathogenic variants were detected only in a single region, and 6 pathogenic variants (p.[Asn3062fs] in EYS, p.[Ala315fs] in EYS, p.[Arg872fs] in RP1, p.[Ala126Val] in RDH12, p.[Arg41Trp] in CRX, and p.[Gly381fs] in PRPF31) were frequently found in ≥ 4 patients in the single region. Conclusion: We observed region-specific pathogenic variants in the Japanese population. Further investigations of causative genes in multiple regions in Japan will contribute to the expansion of the catalog of genetic variants causing RP.

DOI： 10.1007/s10384-021-00824-w

日本網膜色素変性レジストリプロジェクトに登録されたデータの解析

池田康博, 山本修一, 村上晶, 高橋政代, 川崎良, 西口康二, 坂本泰二, 山下英俊

日本眼科学会雑誌 125 巻 ( 4 ) 頁： 425 - 430 2021年4月

記述言語：日本語出版者・発行元：(公財)日本眼科学会

目的:網膜色素変性(RP)は現時点で有効な治療法のない難病で,新規の治療法開発が最も切望されている疾患の一つである.RPの基礎研究・治療研究を推進するために立ち上げた,RPおよびその類縁疾患に特化した患者レジストリである日本網膜色素変性レジストリプロジェクト(Japan Retinitis Pigmentosa Registry Project:JRPRP)の現状と登録されたデータの集計結果を報告する.対象と方法:2018年7月〜2020年3月までにJRPRPに登録されたRP患者1,817名の患者背景を検討した.結果:JRPRPに参加している25施設中13施設から登録があった.性別は男性851名,女性966名.年齢は55.0±17.4歳(平均値±標準偏差).病型の内訳は定型RP1,563名,錐体杆体ジストロフィ62名,無色素性RP59名,中心型・傍中心型RP37名,クリスタリン網膜症18名,Usher症候群15名,コロイデレミア14名,その他34名,不明15名であった.遺伝形式は常染色体優性遺伝12.7%,常染色体劣性遺伝18.5%,伴性劣性遺伝1.7%,孤発型64.3%,不明2.9%であった.定型RPの病因遺伝子診断率は44.3%で,EYS遺伝子異常が最も多かった.さらに,EYS遺伝子異常の患者はほかの常染色体劣性遺伝の患者より視力が良好な傾向がみられた.結論:JRPRPに登録された患者の遺伝形式の割合は既報と同程度であった.同様に,病因遺伝子としてはEYS遺伝子異常が最も多いことが分かった.さらなる患者データの集積により,本邦のRP患者の特徴が明らかとなることが予想される.(著者抄録)

A hypomorphic variant in EYS detected by genome-wide association study contributes toward retinitis pigmentosa 国際誌

Nishiguchi, KM; Miya, F; Mori, Y; Fujita, K; Akiyama, M; Kamatani, T; Koyanagi, Y; Sato, K; Takigawa, T; Ueno, S; Tsugita, M; Kunikata, H; Cisarova, K; Nishino, J; Murakami, A; Abe, T; Momozawa, Y; Terasaki, H; Wada, Y; Sonoda, KH; Rivolta, C; Tsunoda, T; Tsujikawa, M; Ikeda, Y; Nakazawa, T

COMMUNICATIONS BIOLOGY 4 巻 ( 1 ) 頁： 140 - 140 2021年1月

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

The genetic basis of Japanese autosomal recessive retinitis pigmentosa (ARRP) remains largely unknown. Herein, we applied a 2-step genome-wide association study (GWAS) in 640 Japanese patients. Meta-GWAS identified three independent peaks at P < 5.0 × 10−8, all within the major ARRP gene EYS. Two of the three were each in linkage disequilibrium with a different low frequency variant (allele frequency < 0.05); a known founder Mendelian mutation (c.4957dupA, p.S1653Kfs*2) and a non-synonymous variant (c.2528 G > A, p.G843E) of unknown significance. mRNA harboring c.2528 G > A failed to restore rhodopsin mislocalization induced by morpholino-mediated knockdown of eys in zebrafish, consistent with the variant being pathogenic. c.2528 G > A solved an additional 7.0% of Japanese ARRP cases. The third peak was in linkage disequilibrium with a common non-synonymous variant (c.7666 A > T, p.S2556C), possibly representing an unreported disease-susceptibility signal. GWAS successfully unraveled genetic causes of a rare monogenic disorder and identified a high frequency variant potentially linked to development of local genome therapeutics.

DOI： 10.1038/s42003-021-01662-9

EULERIAN FORMULATION USING LAGRANGIAN MARKER PARTICLES WITH REFERENCE MAP TECHNIQUE FOR FLUID-STRUCTURE INTERACTION PROBLEM

Ocular microcirculation changes, measured with laser speckle flowgraphy and optical coherence tomography angiography, in branch retinal vein occlusion with macular edema treated by ranibizumab. 国際誌

Asano T, Kunikata H, Yasuda M, Nishiguchi KM, Abe T, Nakazawa T

International ophthalmology 41 巻 ( 1 ) 頁： 151 - 162 2021年1月

Shimada T., Nishiguchi K., Peco C., Okazawa S., Tsubokura M.

9th International Conference on Computational Methods for Coupled Problems in Science and Engineering, COUPLED PROBLEMS 2021 2021年

出版者・発行元：9th International Conference on Computational Methods for Coupled Problems in Science and Engineering, COUPLED PROBLEMS 2021

Full Eulerian methods constitute a family of numerical techniques used to simulate fluid-structure interaction problems. In a full Eulerian method, the velocity gradient tensor is used to compute deformation of solid. However, it is difficult to compute solid stress accurately near the interface, where the velocity between fluid and solid changes drastically. In this work, we propose an Eulerian formulation for fluid-structure interaction problems using Lagrangian marker particles with the Reference Map Technique to compute the deformation of solid accurately near material interfaces without using the gradient of the velocity. We illustrate and validate the proposed method through the presentation of various benchmark problems.

A case of delayed-onset endophthalmitis due to intraocular iron foreign body detected by MRI

Nitta F., Kunikata H., Nishiguchi K., Abe T., Nakazawa T.

Japanese Journal of Clinical Ophthalmology 75 巻 ( 7 ) 頁： 947 - 952 2021年

出版者・発行元：Japanese Journal of Clinical Ophthalmology

Purpose : To report a case of intraocular iron foreign body found by magnetic resonance imaging (MRI). MRI is prohibited in a patient who has metal in the body, and the reports of its images are rare. Case : A 40-year-old man felt pain of the left eye hitting a concrete wall with a chisel. The next day, he underwent a medical examination at the ophthalmology clinic. However, the left eye has no abnormal findings. After 2 months, he noted photophobia on the left eye and presented with mydriasis. The neurologist found intraocular iron foreign body on the left eye by MRI and CT and referred the patient to our clinic. Findings and clinical course : Left visual acuity was 0.8. The anterior chamber and lens were clear. The iris had a part of atrophy. A slightly vitreous opacity and intraocular iron foreign body were found near the ora serrata on the upper side. We selected an observasion because the subjective symptom and the objective symptom were mild. Endophthalmitis occured two and a half months after the accident. Phacoemulsification with aspiration ( without injection of intraocular lens) and vitrectomy were performed on the left eye. Cutibacterium acnes was detected in the culture from the vitreous body. Endophthalmitis was treated by eye drops and intravenous drip of antibiotics. Injection of intraocular lens was performed after 6 months of the accident. Finally, visual acuity recovered to 1.2. Conclusions : MRI should not be perform in a patient who cannot be denied with intraocular iron foreign body. However, we unexpectedlly obtained the characteristic MRI images.

Clinical characteristics and high resolution retinal imaging of retinitis pigmentosa caused by RP1 gene variants 査読有り

Ueno, S; Koyanagi, Y; Kominami, T; Ito, Y; Kawano, K; Nishiguchi, KM; Rivolta, C; Nakazawa, T; Sonoda, KH; Terasaki, H

JAPANESE JOURNAL OF OPHTHALMOLOGY 64 巻 ( 5 ) 頁： 485 - 496 2020年9月

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

Purpose: To report the clinical course and high resolution images of autosomal recessive retinitis pigmentosa (RP) associated with a variant of the RP1 gene (c.4052_4053ins328/p.Tyr1352Alafs*9; m1), a high frequency founder variant in Japanese RP patients. Study design: Retrospective case series. Methods: Nine patients from 5 unrelated Japanese families were studied. Five patients had the m1 variant homozygously, and 4 patients had the m1 variant compound heterozygously with another frameshift variant (c.4196delG/p.Cys1399Leufs*5). Ophthalmic examinations including adaptive optics (AO) fundus imaging were performed periodically. Results: The fundus photographs, fundus autofluorescence (FAF) images, and optical coherence tomographic (OCT) images indicated severe retinal degeneration in all the patients involving the macula even at a young age (20 s). The areas of surviving photoreceptors in the central macula were seen as hyper-autofluorescent regions in the FAF images and preserved outer retinal structure in the OCT images; they were identifiable in the AO fundus images in 8 eyes. The borders of the surviving photoreceptor areas were surrounded by hyporeflective clumps, presumably containing melanin, and the size of these areas decreased progressively during the 4-year follow-up period. The disappearance of the surviving photoreceptor areas was associated with complete blindness. Conclusion: Patients with RP associated with the m1 variant have a progressive and severe retinal degeneration that begins at an early age. Monitoring the surviving photoreceptor areas by AO fundus imaging can provide a more precise pathological record of retinal degeneration.

DOI： 10.1007/s10384-020-00752-1