Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1126/science.1190897

Type

Journal article

Journal

Science

Publication Date

23/07/2010

Volume

329

Pages

413 - 417

Keywords

Animals, Dependovirus, Disease Models, Animal, Evoked Potentials, Visual, Genetic Therapy, Genetic Vectors, Halobacteriaceae, Halorhodopsins, Humans, Light, Mice, Mice, Knockout, Promoter Regions, Genetic, Retina, Retinal Cone Photoreceptor Cells, Retinal Ganglion Cells, Retinitis Pigmentosa, Tissue Culture Techniques, Transfection, Vision, Ocular, Visual Pathways