Details of a Researcher - Shinmura, Shigeto

Shinmura, Shigeto

写真a

Affiliation: School of Medicine, Department of Ophthalmology （Shinanomachi）

Position: Associate Professor

Related Websites

http://shimmura.net/top/

External Links

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Academic Background 【 Display / hide 】

1989.03

Keio University, 医学部

Graduated

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Research Areas 【 Display / hide 】

Ophthalmology

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Papers 【 Display / hide 】

Global consensus on definition, classification, diagnosis, and staging of limbal stem cell deficiency

Deng S., Borderie V., Chan C., Dana R., Figueiredo F., Gomes J., Pellegrini G., Shimmura S., Kruse F.

Cornea （Cornea) 38 （ 3 ） 364 - 375 2019.03

ISSN 02773740

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© 2018 Wolters Kluwer Health, Inc. All rights reserved. Purpose: Despite extensive knowledge gained over the last 3 decades regarding limbal stem cell deficiency (LSCD), the disease is not clearly defined, and there is lack of agreement on the diagnostic criteria, staging, and classification system among treating physicians and research scientists working on this field. There is therefore an unmet need to obtain global consensus on the definition, classification, diagnosis, and staging of LSCD. Methods: A Limbal Stem Cell Working Group was first established by The Cornea Society in 2012. The Working Group was divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to obtain agreement on a strategic plan and methodology from all participants after a comprehensive literature search, and final agreement was reached on the definition, classification, diagnosis, and staging of LSCD. A writing group was formed to draft the current manuscript, which has been extensively revised to reflect the consensus of the Working Group. Results: A consensus was reached on the definition, classification, diagnosis, and staging of LSCD. The clinical presentation and diagnostic criteria of LSCD were clarified, and a staging system of LSCD based on clinical presentation was established. Conclusions: This global consensus provides a comprehensive framework for the definition, classification, diagnosis, and staging of LSCD. The newly established criteria will aid in the correct diagnosis and formulation of an appropriate treatment for different stages of LSCD, which will facilitate a better understanding of the condition and help with clinical management, research, and clinical trials in this area.
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Prognosis after lamellar keratoplasty for limbal dermoids using preserved corneas

Yamashita K., Hatou S., Uchino Y., Tsubota K., Shimmura S.

Japanese Journal of Ophthalmology （Japanese Journal of Ophthalmology) 63 （ 1 ） 56 - 64 2019.01

ISSN 00215155

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© 2018, Japanese Ophthalmological Society. Purpose: To evaluate the safety and efficacy of lamellar keratoplasty using preserved donor corneas to treat limbal dermoids. Study design: Retrospective study. Methods: The clinical records of 19 patients with limbal dermoids, who underwent lamellar keratoplasty using preserved corneas that were observed for more than 6 months at the Keio University School of Medicine between January, 2000 and December, 2017, were retrospectively reviewed. We retrospectively analyzed demographics, surgical outcomes, the occurrence of any surgically induced changes in refraction, and intra and postoperative complications. Results: Patient age at surgery showed 2 peaks, the first ranged from 0 to 6 years, and the second from 13 to 20 years. All patients except one had good cosmetic results. Preoperative astigmatism was more than 2 diopters in 12 of 16 eyes for which refractive data were recorded. The refractive cylinder in 8 of the 16 eyes differed after surgery by less than 2 diopters. Treatment of amblyopia by occlusion of the fellow eye and spectacle prescription was done either prior to or following surgery, and resulted in improved visual acuity in 7 patients. Intraoperative complications did not occur in any of the patients. Postoperatively, all patients except one showed corneal re-epithelialization within a week. Conclusion: Lamellar keratoplasty using preserved corneas for limbal dermoid yields good cosmetic results. However, improvements in astigmatism and visual acuity are not guaranteed. Preoperative treatment of amblyopia gives a better prognosis for improved visual acuity postoperatively. Long-term observation including amblyopia treatment is required before and after surgery.
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Immunological Properties of Neural Crest Cells Derived from Human Induced Pluripotent Stem Cells

Fujii S., Yoshida S., Inagaki E., Hatou S., Tsubota K., Takahashi M., Shimmura S., Sugita S.

Stem Cells and Development （Stem Cells and Development) 28 （ 1 ） 28 - 43 2019.01

ISSN 15473287

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© Shota Fujii et al. 2018; Published by Mary Ann Liebert, Inc. 2018. Collecting sufficient quantities of primary neural crest cells (NCCs) for experiments is difficult, as NCCs are embryonic transient tissue that basically does not proliferate. We successfully induced NCCs from human induced pluripotent stem cells (iPSCs) in accordance with a previously described method with some modifications. The protocol used in this study efficiently produced large amounts of iPSC-derived NCCs (iPSC-NCCs). Many researchers have recently produced large amounts of iPSC-NCCs and used these to examine the physiological properties, such as migratory activity, and the potential for medical uses such as wound healing. Immunological properties of NCCs are yet to be reported. Therefore, the purpose of this study was to assess the immunological properties of human iPSC-NCCs. Our current study showed that iPSC-NCCs were hypoimmunogenic and had immunosuppressive properties in vitro. Expression of HLA class I molecules on iPSC-NCCs was lower than that observed for iPSCs, and there was no expression of HLA class II and costimulatory molecules on the cells. With regard to the immunosuppressive properties, iPSC-NCCs greatly inhibited T cell activation (cell proliferation and production of inflammatory cytokines) after stimulation. iPSC-NCCs constitutively expressed membrane-bound TGF-β, and TGF-β produced by iPSC-NCCs played a critical role in T cell suppression. Thus, cultured human NCCs can fully suppress T cell activation in vitro. This study may contribute to the realization of using stem cell-derived NCCs in cell-based medicine.
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Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging of Key Proteins in Corneal Samples from Lattice Dystrophy Patients with TGFBI-H626R and TGFBI-R124C Mutations

Venkatraman A., Hochart G., Bonnel D., Stauber J., Shimmura S., Rajamani L., Pervushin K., Mehta J.

Proteomics - Clinical Applications （Proteomics - Clinical Applications) 13 （ 1 ） 2019.01

ISSN 18628346

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© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Scope: The purpose of this study is to identify and visualize the spatial distribution of proteins present in amyloid corneal deposits of TGFBI-CD patients using Mass Spectrometry Imaging (MSI) and compare it with healthy control cornea. Corneal Dystrophies (CD) constitute a group of genetically inherited protein aggregation disorders that affects different layers of the cornea. With accumulated protein deposition, the cornea becomes opaque with decreased visual acuity. CD affecting the stroma and Bowman's membrane, is associated with mutations in transforming growth factor β-induced (TGFBI) gene. Methods: MALDI-Mass Spectrometry Imaging (MSI) is performed on 2 patient corneas and is compared with 1 healthy control cornea using a 7T-MALDI-FTICR. Molecular images obtained are overlaid with congo-red stained sections to visualize the proteins associated with the corneal amyloid aggregates. Results: MALDI-MSI provides a relative abundance and two dimensional spatial protein signature of key proteins (TGFBIp, Apolipoprotein A-I, Apolipoprotein A-IV, Apolipoprotein E, Kaliocin-1, Pyruvate Kinase and Ras related protein Rab-10) in the patient deposits compared to the control. This is the first report of the anatomical localization of key proteins on corneal tissue section from CD patients. This may provide insight in understanding the mechanism of amyloid fibril formation in TGFBI-corneal dystrophy.
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A Rabbit Corneal Endothelial Dysfunction Model Using Endothelial-Mesenchymal Transformed Cells

Yamashita K., Hatou S., Inagaki E., Higa K., Tsubota K., Shimmura S.

Scientific Reports （Scientific Reports) 8 （ 1 ） 2018.12

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© 2018, The Author(s). Unlike humans, rabbit corneal endothelial wounds are known to spontaneously heal. The current study was aimed to develop a new rabbit bullous keratopathy model using corneal endothelial cells that were induced to undergo endothelial-mesenchymal transformation (EMT). EMT was induced in rabbit corneal endothelial cells (RCECs) by culturing with TGFβ and basic FGF Supplemented Medium. The corneal endothelia in recipient rabbits were mechanically scraped from the corneal endothelial surface inside an 8 mm mark. Then, a suspension of EMT-induced RCECs (EMT-RCECs) was injected into the anterior chamber. Eyes injected with freshly isolated RCECs (Fresh RCECs group) and eyes that were scraped without injection of cells (Scrape group) were used as controls. Immediately following operation, subepithelial and stromal edema was observed with increased central corneal thickness and corneal opacity in all groups. In the EMT-RCECs group, bullous keratopathy persisted for 42 days up to the end of the study. In the Fresh-RCECs and Scrape groups, corneal transparency and thickness recovered by 7 days after treatment and was maintained up to 42 days. The activated fibroblast marker, α-SMA, was observed spanning from corneal endothelium to corneal stroma in the EMT-RCECs group. Interestingly, α-SMA was upregulated in the Scrape-group as well. In all groups, there was no damage to other intraocular structures, and intraocular pressure was normal throughout the observation period. Transplanting a fresh donor cornea effectively treated corneal edema due to bullous keratopathy. This model is a promising tool for pre-clinical trials in the development of new therapies against corneal endothelial dysfunction.
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Papers, etc., Registered in KOARA 【 Display / hide 】

Elucidating the pathogenesis of Fuchs corneal dystrophy using disease iPSCs

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2018
Immunological properties of corneal endothelial cells derived from human induced pluripotent stem cells

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2017
Label retaining cells in long term cultured confluent epithelial cell sheets

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2016
A significant role of senescent cells and donor mesenchymal stem cells in ocular chronic graft-versus-host disease and development of new therapy

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2016
Melanocyte stem cells as a niche for corneal epithelial stem cells

Shinmura, Shigeto

科学研究費補助金研究成果報告書 2014

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

ドラッグ・リポジショニングによるフックス角膜変性症治療薬の開発

2019.04

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2022.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, 榛村　重人, Grant-in-Aid for Scientific Research (C), Principal Investigator
フックス角膜内皮変性症の疾患特異的iPS細胞による病態解明

2016.04

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2019.03

MEXT,JSPS, Grant-in-Aid for Scientific Research, 榛村　重人, Grant-in-Aid for Scientific Research (C), Principal Investigator