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PMID: 23319618 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Reprogramming of adult rod photoreceptors prevents retinal degeneration.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 110 ·No. 5 ·2013-01-29 ·Pages 1732-7

Montana CL, Kolesnikov AV, Shen SQ, Myers CA, Kefalov VJ, Corbo JC

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.

MeSH Terms
Animals Basic-Leucine Zipper Transcription Factors/deficiency,genetics CpG Islands/genetics DNA Methylation Electroretinography Eye Proteins/genetics Gene Expression Immunohistochemistry In Situ Hybridization Mice Mice, Inbred C57BL Mice, Knockout Microscopy, Electron Retina/metabolism,pathology Retinal Cone Photoreceptor Cells/metabolism,ultrastructure Retinal Degeneration/genetics,metabolism,physiopathology Retinal Rod Photoreceptor Cells/metabolism,ultrastructure Retinitis Pigmentosa/genetics,metabolism,physiopathology Reverse Transcriptase Polymerase Chain Reaction Rhodopsin/deficiency,genetics
Chemicals
Basic-Leucine Zipper Transcription Factors Eye Proteins Nrl protein, mouse Rhodopsin
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Montana Cynthia L
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kolesnikov Alexander V
Shen Susan Q
Myers Connie A
Kefalov Vladimir J
Corbo Joseph C
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
DOI
10.1073/pnas.1214387110
Published
2013-01-29
Epub
2013-00-14
Pages
1732-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3562787
Subset
IM
Grants
NEI NIH HHS · P30 EY002687 · United States
NEI NIH HHS · R01 EY018826 · United States
NEI NIH HHS · EY019312 · United States
NEI NIH HHS · EY018826 · United States
NINDS NIH HHS · NS057105 · United States
NCI NIH HHS · P30 CA091842 · United States
NEI NIH HHS · EY13360 · United States
NCI NIH HHS · CA91842 · United States
NINDS NIH HHS · P30 NS057105 · United States
NEI NIH HHS · EY002687 · United States
NEI NIH HHS · R01 EY019312 · United States
NEI NIH HHS · T32 EY013360 · United States
External Links
PubMed source DOI: 10.1073/pnas.1214387110 PMC Full Text View journal details
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