Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy

Abstract Cones are responsible for daylight, central, high acuity and color vision. Three proteins found in human cones, i.e. long-wavelength (L)-, middle-wavelength (M)-, and short-wavelength sensitive (S)-opsins, are responsible for red, green and blue color recognition, respectively. Human blue c...

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Autores principales:	Yuxin Zhang, Wen-Tao Deng, Wei Du, Ping Zhu, Jie Li, Fan Xu, Jingfen Sun, Cecilia D. Gerstner, Wolfgang Baehr, Sanford L. Boye, Chen Zhao, William W. Hauswirth, Ji-jing Pang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/bc27d7c6a496437cb3861b2557b98e8d
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spelling	oai:doaj.org-article:bc27d7c6a496437cb3861b2557b98e8d2021-12-02T16:06:15ZGene-based Therapy in a Mouse Model of Blue Cone Monochromacy10.1038/s41598-017-06982-72045-2322https://doaj.org/article/bc27d7c6a496437cb3861b2557b98e8d2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06982-7https://doaj.org/toc/2045-2322Abstract Cones are responsible for daylight, central, high acuity and color vision. Three proteins found in human cones, i.e. long-wavelength (L)-, middle-wavelength (M)-, and short-wavelength sensitive (S)-opsins, are responsible for red, green and blue color recognition, respectively. Human blue cone monochromacy (BCM) is characterized by functional loss of both L- and M-cone opsins due to mutations in the OPN1LW/OPN1MW gene cluster on the X chromosome. BCM patients, who rely on their vision from only S-cones and rods, suffer severely reduced visual acuity and impaired color vision. Recent studies show that there is sufficient cone structure remaining in the central fovea of BCM patients to consider AAV-mediated gene augmentation therapy. In contrast, mouse retina has only two opsins, S-opsin and M-opsin, but no L-opsin. We generated an M-opsin knockout mouse (Opn1mw −/−) expressing only S-opsin as a model for human BCM. We show that recombinant M-opsin delivered by AAV5 vectors rescues M-cone function in Opn1mw −/− mice. We also show that AAV delivered M-opsin localizes in the dorsal cone outer segments, and co-localizes with S-opsin in the ventral retina. Our study demonstrates that cones without M-opsin remain viable and respond to gene augmentation therapy, thereby providing proof-of-concept for cone function restoration in BCM patients.Yuxin ZhangWen-Tao DengWei DuPing ZhuJie LiFan XuJingfen SunCecilia D. GerstnerWolfgang BaehrSanford L. BoyeChen ZhaoWilliam W. HauswirthJi-jing PangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yuxin Zhang Wen-Tao Deng Wei Du Ping Zhu Jie Li Fan Xu Jingfen Sun Cecilia D. Gerstner Wolfgang Baehr Sanford L. Boye Chen Zhao William W. Hauswirth Ji-jing Pang Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy
description	Abstract Cones are responsible for daylight, central, high acuity and color vision. Three proteins found in human cones, i.e. long-wavelength (L)-, middle-wavelength (M)-, and short-wavelength sensitive (S)-opsins, are responsible for red, green and blue color recognition, respectively. Human blue cone monochromacy (BCM) is characterized by functional loss of both L- and M-cone opsins due to mutations in the OPN1LW/OPN1MW gene cluster on the X chromosome. BCM patients, who rely on their vision from only S-cones and rods, suffer severely reduced visual acuity and impaired color vision. Recent studies show that there is sufficient cone structure remaining in the central fovea of BCM patients to consider AAV-mediated gene augmentation therapy. In contrast, mouse retina has only two opsins, S-opsin and M-opsin, but no L-opsin. We generated an M-opsin knockout mouse (Opn1mw −/−) expressing only S-opsin as a model for human BCM. We show that recombinant M-opsin delivered by AAV5 vectors rescues M-cone function in Opn1mw −/− mice. We also show that AAV delivered M-opsin localizes in the dorsal cone outer segments, and co-localizes with S-opsin in the ventral retina. Our study demonstrates that cones without M-opsin remain viable and respond to gene augmentation therapy, thereby providing proof-of-concept for cone function restoration in BCM patients.
format	article
author	Yuxin Zhang Wen-Tao Deng Wei Du Ping Zhu Jie Li Fan Xu Jingfen Sun Cecilia D. Gerstner Wolfgang Baehr Sanford L. Boye Chen Zhao William W. Hauswirth Ji-jing Pang
author_facet	Yuxin Zhang Wen-Tao Deng Wei Du Ping Zhu Jie Li Fan Xu Jingfen Sun Cecilia D. Gerstner Wolfgang Baehr Sanford L. Boye Chen Zhao William W. Hauswirth Ji-jing Pang
author_sort	Yuxin Zhang
title	Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy
title_short	Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy
title_full	Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy
title_fullStr	Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy
title_full_unstemmed	Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy
title_sort	gene-based therapy in a mouse model of blue cone monochromacy
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/bc27d7c6a496437cb3861b2557b98e8d
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_version_	1718385049534988288

Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy

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