Night vision restored in days after decades of congenital blindness

Samuel G Jacobson; Artur V Cideciyan; Allen C Ho; Alejandro J Roman; Vivian Wu; Alexandra V Garafalo; Alexander Sumaroka; Arun K Krishnan; Malgorzata Swider; Abraham A Mascio; Christine N Kay; Dan Yoon; Kenji P Fujita; Sanford L Boye; Igor V Peshenko; Alexander M Dizhoor; Shannon E Boye

doi:10.1016/j.isci.2022.105274

Night vision restored in days after decades of congenital blindness

iScience. 2022 Oct 4;25(10):105274. doi: 10.1016/j.isci.2022.105274. eCollection 2022 Oct 21.

Authors

Samuel G Jacobson¹, Artur V Cideciyan¹, Allen C Ho², Alejandro J Roman¹, Vivian Wu¹, Alexandra V Garafalo¹, Alexander Sumaroka¹, Arun K Krishnan¹, Malgorzata Swider¹, Abraham A Mascio¹, Christine N Kay³, Dan Yoon³, Kenji P Fujita³, Sanford L Boye⁴, Igor V Peshenko⁵, Alexander M Dizhoor⁵, Shannon E Boye⁶

Affiliations

¹ Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
² Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA 19107, USA.
³ Atsena Therapeutics, Inc., Durham, NC 27709, USA.
⁴ Department of Pediatrics, Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL 32601, USA.
⁵ Pennsylvania College of Optometry, Salus University, Elkins Park, PA 19027, USA.
⁶ Department of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida College of Medicine, Gainesville, FL 32611, USA.

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.

Keywords: Clinical genetics; Health sciences; Medicine.

Abstract

Grants and funding