ID | 67169 |
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著者 |
Sato, Keita
Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
ORCID
Kaken ID
publons
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Liu, Yang
Department of Cytology and Histology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
Yamashita, Takahiro
Department of Biophysics, Graduate School of Science, Kyoto University
Ohuchi, Hideyo
Department of Cytology and Histology, Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University
ORCID
Kaken ID
researchmap
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抄録 | Eyes shut homolog (EYS) encodes a proteoglycan and the human mutation causes retinitis pigmentosa type 25 (RP25) with progressive retinal degeneration. RP25 most frequently affects autosomal recessive RP patients with many ethnic backgrounds. Although studies using RP models have facilitated the development of therapeutic medications, Eys has been lost in rodent model animals. Here we examined the roles for Eys in the maintenance of photoreceptor structure and function by generating eys-null medaka fish using the CRISPR-Cas9 system. Medaka EYS protein was present near the connecting cilium of wild-type photoreceptors, while it was absent from the eys−/− retina. The mutant larvae exhibited a reduced visual motor response compared with wild-type. In contrast to reported eys-deficient zebrafish at the similar stage, no retinal cell death was detected in the 8-month post-hatching (8-mph) medaka eys mutant. Immunohistochemistry showed a significant reduction in the length of cone outer segments (OSs), retention of OS proteins in the inner segments of photoreceptors, and abnormal filamentous actin network at the base of cone OSs in the mutant retina by 8 mph. Electron microscopy revealed aberrant structure of calyceal processes, numerous vesiculation and lamellar interruptions, and autophagosomes in the eys-mutant cone photoreceptors. In situ hybridization showed an autophagy component gene, gabarap, was ectopically expressed in the eys-null retina. These results suggest eys is required for regeneration of OS, especially of cone photoreceptors, and transport of OS proteins by regulating actin filaments. Enhanced autophagy may delay the progression of retinal degeneration when lacking EYS in the medaka retina.
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キーワード | Eyes shut homolog
Eys
Retinitis pigmentosa
RP25
Cone photoreceptor
Autophagy
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備考 | This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s00441-022-03702-0
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発行日 | 2022-11-22
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出版物タイトル |
Cell and Tissue Research
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巻 | 391巻
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号 | 2号
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出版者 | Springer Science and Business Media LLC
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開始ページ | 249
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終了ページ | 267
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ISSN | 0302-766X
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NCID | AA00600105
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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 | © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022
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論文のバージョン | author
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関連URL | isVersionOf https://doi.org/10.1007/s00441-022-03702-0
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Citation | Sato, K., Liu, Y., Yamashita, T. et al. The medaka mutant deficient in eyes shut homolog exhibits opsin transport defects and enhanced autophagy in retinal photoreceptors. Cell Tissue Res 391, 249–267 (2023). https://doi.org/10.1007/s00441-022-03702-0
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助成機関名 |
Japan Society for the Promotion of Science
Takeda Science Foundation
Okayama Medical Foundation
Astellas Pharma Inc.
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助成番号 | 20K08885
20K21655
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