Restoration of high-sensitivity and adapting vision with a cone opsin.

Abstract

Inherited and age-related retinal degenerative diseases cause progressive loss of rod and cone photoreceptors, leading to blindness, but spare downstream retinal neurons, which can be targeted for optogenetic therapy. However, optogenetic approaches have been limited by either low light sensitivity or slow kinetics, and lack adaptation to changes in ambient light, and not been shown to restore object vision. We find that the vertebrate medium wavelength cone opsin (MW-opsin) overcomes these limitations and supports vision in dim light. MW-opsin enables an otherwise blind retinitis pigmenotosa mouse to discriminate temporal and spatial light patterns displayed on a standard LCD computer tablet, displays adaption to changes in ambient light, and restores open-field novel object exploration under incidental room light. By contrast, rhodopsin, which is similar in sensitivity but slower in light response and has greater rundown, fails these tests. Thus, MW-opsin provides the speed, sensitivity and adaptation needed to restore patterned vision.

• Authors: Michael H Berry, Amy Holt, Autoosa Salari, Julia Veit, Meike Visel, Joshua Levitz, Krisha Aghi, Benjamin M Gaub, Benjamin Sivyer, John G Flannery, Ehud Y Isacoff
• Journal: Nature communications (Nat Commun) Vol. 10 Issue 1 Pg. 1221 (03 15 2019) ISSN: 2041-1723 [Electronic] England
• PMID: 30874546 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cone Opsins
• Rhodopsin

Topics

• Animals
• Blindness (etiology, prevention & control)
• Cell Line
• Cone Opsins (genetics)
• Dependovirus (genetics)
• Disease Models, Animal
• Genetic Therapy (methods)
• Genetic Vectors (administration & dosage, genetics)
• Humans
• Intravitreal Injections
• Keratinocytes
• Mice
• Mice, Inbred C57BL
• Optogenetics (methods)
• Patch-Clamp Techniques
• Retina (pathology)
• Retinal Cone Photoreceptor Cells (pathology)
• Retinal Degeneration (complications, pathology, therapy)
• Rhodopsin (genetics)
• Treatment Outcome