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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-06982-7 |
| _version_ | 1818430740607533056 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-14T15:38:13Z |
| format | Article |
| id | doaj.art-bc27d7c6a496437cb3861b2557b98e8d |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T15:38:13Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-bc27d7c6a496437cb3861b2557b98e8d2022-12-21T22:55:41ZengNature PortfolioScientific Reports2045-23222017-07-01711810.1038/s41598-017-06982-7Gene-based Therapy in a Mouse Model of Blue Cone MonochromacyYuxin Zhang0Wen-Tao Deng1Wei Du2Ping Zhu3Jie Li4Fan Xu5Jingfen Sun6Cecilia D. Gerstner7Wolfgang Baehr8Sanford L. Boye9Chen Zhao10William W. Hauswirth11Ji-jing Pang12Ophthalmology, University of FloridaOphthalmology, University of FloridaOphthalmology, University of FloridaOphthalmology, University of FloridaOphthalmology, University of FloridaOphthalmology, University of FloridaOphthalmology, University of FloridaOpthalmology and Visual Sciences, University of UtahOpthalmology and Visual Sciences, University of UtahOphthalmology, University of FloridaDepartment of Ophthalmology, First Affiliated Hospital, Nanjing Medical UniversityOphthalmology, University of FloridaOphthalmology, University of FloridaAbstract 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.https://doi.org/10.1038/s41598-017-06982-7 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | Gene-based Therapy in a Mouse Model of Blue Cone Monochromacy |
| title_sort | gene based therapy in a mouse model of blue cone monochromacy |
| url | https://doi.org/10.1038/s41598-017-06982-7 |
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