ID | 63001 |
フルテキストURL | |
著者 |
Liu, Shihui
Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
Miyaji, Mary
Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hosoya, Osamu
Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Matsuo, Toshihiko
Department of Ophthalmology, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University
ORCID
Kaken ID
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抄録 | Purpose: NK-5962 is a key component of photoelectric dye-coupled polyethylene film, designated Okayama University type-retinal prosthesis (OUReP™). Previously, we found that NK-5962 solution could reduce the number of apoptotic photoreceptors in the eyes of the Royal College of Surgeons (RCS) rats by intravitreal injection under a 12 h light/dark cycle. This study aimed to explore possible molecular mechanisms underlying the anti-apoptotic effect of NK-5962 in the retina of RCS rats. Methods: RCS rats received intravitreal injections of NK-5962 solution in the left eye at the age of 3 and 4 weeks, before the age of 5 weeks when the speed in the apoptotic degeneration of photoreceptors reaches its peak. The vehicle-treated right eyes served as controls. All rats were housed under a 12 h light/dark cycle, and the retinas were dissected out at the age of 5 weeks for RNA sequence (RNA-seq) analysis. For the functional annotation of differentially expressed genes (DEGs), the Metascape and DAVID databases were used. Results: In total, 55 up-regulated DEGs, and one down-regulated gene (LYVE1) were found to be common among samples treated with NK-5962. These DEGs were analyzed using Gene Ontology (GO) term enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome pathway analyses. We focused on the up-regulated DEGs that were enriched in extracellular matrix organization, extracellular exosome, and PI3K–Akt signaling pathways. These terms and pathways may relate to mechanisms to protect photoreceptor cells. Moreover, our analyses suggest that SERPINF1, which encodes pigment epithelium-derived factor (PEDF), is one of the key regulatory genes involved in the anti-apoptotic effect of NK-5962 in RCS rat retinas. Conclusions: Our findings suggest that photoelectric dye NK-5962 may delay apoptotic death of photoreceptor cells in RCS rats by up-regulating genes related to extracellular matrix organization, extracellular exosome, and PI3K–Akt signaling pathways. Overall, our RNA-seq and bioinformatics analyses provide insights in the transcriptome responses in the dystrophic RCS rat retinas that were induced by NK-5962 intravitreal injection and offer potential target genes for developing new therapeutic strategies for patients with retinitis pigmentosa.
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キーワード | apoptosis
drug
retina
photoreceptors
retinitis pigmentosa
extracellular exosome
extracellular matrix organization
PI3K–Akt signaling pathway
SERPINF1
pigment epithelium-derived factor (PEDF)
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発行日 | 2021-12-10
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出版物タイトル |
International Journal of Molecular Sciences
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巻 | 22巻
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号 | 24号
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出版者 | MDPI
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開始ページ | 13276
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ISSN | 1422-0067
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NCID | AA12038549
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資料タイプ |
学術雑誌論文
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言語 |
英語
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OAI-PMH Set |
岡山大学
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著作権者 | © 2021 by the authors.
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論文のバージョン | publisher
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DOI | |
関連URL | isVersionOf https://doi.org/10.3390/ijms222413276
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ライセンス | https://creativecommons.org/licenses/by/4.0/
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Citation | Liu, S.; Miyaji, M.; Hosoya, O.; Matsuo, T. Effect of NK-5962 on Gene Expression Profiling of Retina in a Rat Model of Retinitis Pigmentosa. Int. J. Mol. Sci. 2021, 22, 13276. https://doi.org/10.3390/ ijms222413276
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助成機関名 |
Practical Research Program for Rare/Intractable Diseases
Japan Agency for Medical Research and Development (AMED)
Science and Technology Promotion grants
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