Document Detail


Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa.
MedLine Citation:
PMID:  20576849     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Retinitis pigmentosa refers to a diverse group of hereditary diseases that lead to incurable blindness, affecting two million people worldwide. As a common pathology, rod photoreceptors die early, whereas light-insensitive, morphologically altered cone photoreceptors persist longer. It is unknown if these cones are accessible for therapeutic intervention. Here, we show that expression of archaebacterial halorhodopsin in light-insensitive cones can substitute for the native phototransduction cascade and restore light sensitivity in mouse models of retinitis pigmentosa. Resensitized photoreceptors activate all retinal cone pathways, drive sophisticated retinal circuit functions (including directional selectivity), activate cortical circuits, and mediate visually guided behaviors. Using human ex vivo retinas, we show that halorhodopsin can reactivate light-insensitive human photoreceptors. Finally, we identified blind patients with persisting, light-insensitive cones for potential halorhodopsin-based therapy.
Authors:
Volker Busskamp; Jens Duebel; David Balya; Mathias Fradot; Tim James Viney; Sandra Siegert; Anna C Groner; Erik Cabuy; Valérie Forster; Mathias Seeliger; Martin Biel; Peter Humphries; Michel Paques; Saddek Mohand-Said; Didier Trono; Karl Deisseroth; José A Sahel; Serge Picaud; Botond Roska
Related Documents :
20400629 - Electrophysiological assessment of spectral sensitivity in adult nile tilapia oreochrom...
12746869 - Ontogeny of ultraviolet-sensitive cones in the retina of rainbow trout (oncorhynchus my...
6284859 - Induction of dark-adaptive retinomotor movement (cell elongation) in teleost retinal co...
21670099 - The brain structural hub of interhemispheric information integration for visual motion ...
15733959 - Accommodation with and without short-wavelength-sensitive cones and chromatic aberration.
6335939 - Temporal modulation sensitivities of red- and green-sensitive cone systems in dichromats.
19792309 - Repulsive casimir force in chiral metamaterials.
6527929 - Low-level and high-level processes in the perceptual organization of three-dimensional ...
17013889 - Muscle activation assessment: effects of method, stimulus number, and joint angle.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2010-06-24
Journal Detail:
Title:  Science (New York, N.Y.)     Volume:  329     ISSN:  1095-9203     ISO Abbreviation:  Science     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-23     Completed Date:  2010-08-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0404511     Medline TA:  Science     Country:  United States    
Other Details:
Languages:  eng     Pagination:  413-7     Citation Subset:  IM    
Affiliation:
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE22338
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Dependovirus / genetics
Disease Models, Animal
Evoked Potentials, Visual
Gene Therapy*
Genetic Vectors
Halobacteriaceae / genetics
Halorhodopsins / genetics*,  metabolism*
Humans
Light
Mice
Mice, Knockout
Promoter Regions, Genetic
Retina / physiology
Retinal Cone Photoreceptor Cells / physiology*
Retinal Ganglion Cells / physiology
Retinitis Pigmentosa / physiopathology,  therapy*
Tissue Culture Techniques
Transfection
Vision, Ocular
Visual Pathways / physiology
Chemical
Reg. No./Substance:
0/Halorhodopsins
Comments/Corrections
Comment In:
Science. 2010 Jul 23;329(5990):403-4   [PMID:  20651144 ]
Nat Rev Neurosci. 2010 Aug;11(8):534   [PMID:  20672425 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Simulated Rapid Warming of Abyssal North Pacific Waters.
Next Document:  Tissue-Engineered Lungs for in Vivo Implantation.