Night vision restored in days after decades of congenital blindness

• Published in: iScience 2022-10, Vol.25 (10), p.105274-105274, Article 105274
• Main Authors: Jacobson, Samuel G., Cideciyan, Artur V., Ho, Allen C., Roman, Alejandro J., Wu, Vivian, Garafalo, Alexandra V., Sumaroka, Alexander, Krishnan, Arun K., Swider, Malgorzata, Mascio, Abraham A., Kay, Christine N., Yoon, Dan, Fujita, Kenji P., Boye, Sanford L., Peshenko, Igor V., Dizhoor, Alexander M., Boye, Shannon E.
• Format: Article
• Language: English
• Subjects: Clinical genetics; Health sciences; Medicine
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2022.105274

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. [Display omitted] •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