Format

Send to

Choose Destination
Sci Rep. 2017 Jul 27;7(1):6690. doi: 10.1038/s41598-017-06982-7.

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

Author information

1
Ophthalmology, University of Florida, Gainesville, FL, USA.
2
Department of Ophthalmology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
3
Ophthalmology Department of Peking University People's Hospital, Peking University People's Eye Center and Eye Institute, Beijing, China.
4
Department of Ophthalmology, People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
5
Department of Obstetrics and Gynecology, Shanxi Dayi Hospital, Taiyuan, Shanxi Province, China.
6
Opthalmology and Visual Sciences, University of Utah, Salt Lake City, UT, USA.
7
Department of Ophthalmology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. dr_zhaochen@163.com.
8
Department of Ophthalmology and Vision Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China. dr_zhaochen@163.com.
9
Ophthalmology, University of Florida, Gainesville, FL, USA. hauswrth@ufl.edu.
10
Ophthalmology, University of Florida, Gainesville, FL, USA. jpang@ufl.edu.
11
Department of Ophthalmology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, China. jpang@ufl.edu.
12
Xiamen Eye Center of Xiamen University, Xiamen, Fujian, China. jpang@ufl.edu.

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.

PMID:
28751656
PMCID:
PMC5532293
DOI:
10.1038/s41598-017-06982-7
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center