The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases

Varner, Leah Rie; Chaya, Taro; Maeda, Yamato; Tsutsumi, Ryotaro; Zhou, Shanshan; Tsujii, Toshinori; Okuzaki, Daisuke; Furukawa, Takahisa

doi:https://doi.org/10.1016/j.isci.2024.109380

The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases

Varner, Leah Rie; Chaya, Taro; Maeda, Yamato et al.

iScience, 2024, 27(4), 109380

Number of Access:898（2025-08-18 18:47 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/95642

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Title	The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases
Creator	CreatorName Varner, Leah Rie
	NRID 1000050747087 1000050747087 researchmap permalink chaya chaya Scopus Author ID 37094720600 37094720600 CreatorName Chaya, Taro
	CreatorName Maeda, Yamato
	NRID 1000070965706 1000070965706 CreatorName Tsutsumi, Ryotaro
	CreatorName Zhou, Shanshan
	CreatorName Tsujii, Toshinori
	NRID 1000000346131 1000000346131 ORCID 0000-0002-4552-783X 0000-0002-4552-783X researchmap permalink read0092307 read0092307 Scopus Author ID 6506703054 6506703054 CreatorName Okuzaki, Daisuke
	NRID 1000050260609 1000050260609 researchmap permalink read0083689 read0083689 Scopus Author ID 7403160171 7403160171 ORCID 0000-0003-4171-220X 0000-0003-4171-220X CreatorName Furukawa, Takahisa
Subject	Cell biology
	Cellular neuroscience
	Molecular biology
	Molecular neuroscience
	Neuroscience
Description	Varner L.R., Chaya T., Maeda Y., et al. The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases. iScience 27, 109380 (2024); https://doi.org/10.1016/j.isci.2024.109380.
Abstract	Primary and secondary cone photoreceptor death in retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP), leads to severe visual impairment and blindness. Although the cone photoreceptor protection in retinal degenerative diseases is crucial for maintaining vision, the underlying molecular mechanisms are unclear. Here, we found that the deubiquitinase Otud7b/Cezanne is predominantly expressed in photoreceptor cells in the retina. We analyzed Otud7b−/− mice, which were subjected to light-induced damage, a dry AMD model, or were mated with an RP mouse model, and observed increased cone photoreceptor degeneration. Using RNA-sequencing and bioinformatics analysis followed by a luciferase reporter assay, we found that Otud7b downregulates NF-κB activity. Furthermore, inhibition of NF-κB attenuated cone photoreceptor degeneration in the light-exposed Otud7b−/− retina and stress-induced neuronal cell death resulting from Otud7b deficiency. Together, our findings suggest that Otud7b protects cone photoreceptors in retinal degenerative diseases by modulating NF-κB activity.
Publisher	Elsevier Inc.
Source Title	iScience
Volume (Issue)	27(4)
Page	109380
Date of Issued	2024-04-19
Language	English
Handle URL	https://hdl.handle.net/11094/95642
eISSN	25890042
Relation.isIdenticalTo	DOI (Publisher Version) https://doi.org/10.1016/j.isci.2024.109380
Access Rights	open access
CopyRight	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
oaire:version	Version of Record
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	iScience. 2024, 27(4), p. 109380
DC.title	The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases
DC.creator	Varner, Leah Rie
	Chaya, Taro
	Maeda, Yamato
	Tsutsumi, Ryotaro
	Zhou, Shanshan
	Tsujii, Toshinori
	Okuzaki, Daisuke
	Furukawa, Takahisa
DC.publisher	Elsevier Inc.
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2024-04-19
DC.identifier	https://doi.org/10.1016/j.isci.2024.109380
DC.subject	Cell biology
	Cellular neuroscience
	Molecular biology
	Molecular neuroscience
	Neuroscience
DC.description	Varner L.R., Chaya T., Maeda Y., et al. The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases. iScience 27, 109380 (2024); https://doi.org/10.1016/j.isci.2024.109380.
DCTERMS.abstract	Primary and secondary cone photoreceptor death in retinal degenerative diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP), leads to severe visual impairment and blindness. Although the cone photoreceptor protection in retinal degenerative diseases is crucial for maintaining vision, the underlying molecular mechanisms are unclear. Here, we found that the deubiquitinase Otud7b/Cezanne is predominantly expressed in photoreceptor cells in the retina. We analyzed Otud7b−/− mice, which were subjected to light-induced damage, a dry AMD model, or were mated with an RP mouse model, and observed increased cone photoreceptor degeneration. Using RNA-sequencing and bioinformatics analysis followed by a luciferase reporter assay, we found that Otud7b downregulates NF-κB activity. Furthermore, inhibition of NF-κB attenuated cone photoreceptor degeneration in the light-exposed Otud7b−/− retina and stress-induced neuronal cell death resulting from Otud7b deficiency. Together, our findings suggest that Otud7b protects cone photoreceptors in retinal degenerative diseases by modulating NF-κB activity.
DC.rights	This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
DC.format	95642
citation_title	The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases
citation_author	Varner, Leah Rie
	Chaya, Taro
	Maeda, Yamato
	Tsutsumi, Ryotaro
	Zhou, Shanshan
	Tsujii, Toshinori
	Okuzaki, Daisuke
	Furukawa, Takahisa
citation_publisher	Elsevier Inc.
citation_language	English
citation_date	2024-04-19
citation_journal_title	iScience
citation_volume	27
citation_issue	4
citation_firstpage	109380
citation_doi	https://doi.org/10.1016/j.isci.2024.109380
citation_public_url	https://hdl.handle.net/11094/95642

The deubiquitinase Otud7b suppresses cone photoreceptor degeneration in mouse models of retinal degenerative diseases

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