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
Affiliations
Samuel G. Jacobson
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Corresponding author
Artur V. Cideciyan
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Allen C. Ho
Wills Eye Hospital, Thomas Jefferson University, Philadelphia, PA 19107, USA
Alejandro J. Roman
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Vivian Wu
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Alexandra V. Garafalo
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Alexander Sumaroka
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Arun K. Krishnan
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Malgorzata Swider
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Abraham A. Mascio
Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
Christine N. Kay
Atsena Therapeutics, Inc., Durham, NC 27709, USA
Dan Yoon
Atsena Therapeutics, Inc., Durham, NC 27709, USA
Kenji P. Fujita
Atsena Therapeutics, Inc., Durham, NC 27709, USA
Sanford L. Boye
Department of Pediatrics, Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL 32601, USA
Igor V. Peshenko
Pennsylvania College of Optometry, Salus University, Elkins Park, PA 19027, USA
Alexander M. Dizhoor
Pennsylvania College of Optometry, Salus University, Elkins Park, PA 19027, USA
Shannon E. Boye
Department of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida College of Medicine, Gainesville, FL 32611, USA
Summary: 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.
