期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 5, 页码 1732-1737出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1214387110
关键词
transdifferentiation; rhodopsin; rd1
资金
- National Cancer Institute Cancer Center [CA91842]
- National Institutes of Health [EY002687]
- Neuroscience Blueprint Interdisciplinary Center [NS057105]
- National Eye Institute [EY018826, EY019312]
- Institutional Vision Science Training Grant [EY13360]
- Research to Prevent Blindness
A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa is one of the most common degenerative diseases of the eye and is associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown of the rod photoreceptor determinant Nrl, could make the cells resistant to the effects of mutations in rod-specific genes, thereby preventing secondary cone loss. To test this idea, we engineered a tamoxifen-inducible allele of Nrl to acutely inactivate the gene in adult rods. This manipulation resulted in reprogramming of rods into cells with a variety of cone-like molecular, histologic, and functional properties. Moreover, reprogramming of adult rods achieved cellular and functional rescue of retinal degeneration in a mouse model of retinitis pigmentosa. These findings suggest that elimination of Nrl in adult rods may represent a unique therapy for retinal degeneration.
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