Journal article
Night vision restored in days after decades of congenital blindness
iScience, v 25(10), 105274
21 Oct 2022
PMID: 36274938
Abstract
Signaling of vision to the brain starts with the retinal phototransduction cascade which converts visible light from the environment into chemical changes. Vision impairment results when mutations inactivate proteins of the phototransduction cascade. A severe monogenically inherited blindness, Leber congenital amaurosis (LCA), is caused by mutations in the GUCY2D gene, leading to a molecular defect in the production of cyclic GMP, the second messenger of phototransduction. We studied two patients with GUCY2D-LCA who were undergoing gene augmentation therapy. Both patients had large deficits in rod photoreceptor-based night vision before intervention. Within days of therapy, rod vision in both patients changed dramatically; improvements in visual function and functional vision in these hyper-responding patients reached more than 3 log10 units (1000-fold), nearing healthy rod vision. Quick activation of the complex molecular pathways from retinal photoreceptor to visual cortex and behavior is thus possible in patients even after being disabled and dormant for decades.
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•Phototransduction, the biochemical cascade in photoreceptors, initiates vision•Congenital blindness can be due to defective phototransduction (GUCY2D gene mutations)•GUCY2D gene therapy (low dose) suggested some efficacy after months post-treatment•Higher dose therapy now shows log units of improved night (rod) vision over days
Clinical genetics; Health sciences; Medicine
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13 Record Views
27 citations in Scopus
Details
- Title
- Night vision restored in days after decades of congenital blindness
- Creators
- Samuel G. Jacobson - Penn Presbyterian Medical CenterArtur V. Cideciyan - Penn Presbyterian Medical CenterAllen C. Ho - Wills Eye HospitalAlejandro J. Roman - Penn Presbyterian Medical CenterVivian Wu - University of PennsylvaniaAlexandra V. Garafalo - Penn Presbyterian Medical CenterAlexander Sumaroka - Penn Presbyterian Medical CenterArun K. Krishnan - Penn Presbyterian Medical CenterMalgorzata Swider - University of PennsylvaniaAbraham A. Mascio - Penn Presbyterian Medical CenterChristine N. Kay - Atsena Therapeutics, Inc., Durham, NC 27709, USADan Yoon - Atsena Therapeutics, Inc., Durham, NC 27709, USAKenji P. Fujita - Atsena Therapeutics, Inc., Durham, NC 27709, USASanford L. Boye - University of FloridaIgor V. Peshenko - Salus UniversityAlexander M. Dizhoor - Salus UniversityShannon E. Boye - Department of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida College of Medicine, Gainesville, FL 32611, USA
- Publication Details
- iScience, v 25(10), 105274
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy; Pennsylvania College of Optometry (PCO)
- Scopus ID
- 2-s2.0-85139865344
- Other Identifier
- 991022035112304721