Journal article
Reprogramming of adult rod photoreceptors prevents retinal degeneration
Proceedings of the National Academy of Sciences - PNAS, Vol.110(5), pp.1732-1737
01/29/2013
DOI: 10.1073/pnas.1214387110
PMCID: PMC3562787
PMID: 23319618
Abstract
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.
Details
- Title: Subtitle
- Reprogramming of adult rod photoreceptors prevents retinal degeneration
- Creators
- Cynthia L. Montana - Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USAAlexander V. Kolesnikov - Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USASusan Q. Shen - Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USAConnie A. Myers - Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USAVladimir J. Kefalov - Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USAJoseph C. Corbo - Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.110(5), pp.1732-1737
- Publisher
- Natl Acad Sciences
- DOI
- 10.1073/pnas.1214387110
- PMID
- 23319618
- PMCID
- PMC3562787
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Number of pages
- 6
- Grant note
- P30CA091842 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30NS057105 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) EY13360 / Institutional Vision Science Training Grant NS057105 / Neuroscience Blueprint Interdisciplinary Center EY018826; EY019312 / National Eye Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) T32EY013360 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) EY002687 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA CA91842 / National Cancer Institute Cancer Center; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Research to Prevent Blindness; Research to Prevent Blindness (RPB)
- Language
- English
- Date published
- 01/29/2013
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984618518502771
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