Seeing color following gene augmentation therapy in achromatopsia

Abstract

How will people who spent their visual lives with only rods respond to cone function restoration? Will they be able suddenly see the colors of the rainbow? CNGA3-achromatopsia is a congenital hereditary disease in which cone dysfunction leads patients to have rod photoreceptor-driven vision only in daylight,^1,2,3,4 seeing the world in blurry shades of gray.^5,6 We studied color perception in four CNGA3-achromatopsia patients following monocular retinal gene augmentation therapy.^7,8,9 Following treatment, although some cortical changes were reported,^3,4 patients did not report a dramatic change in their vision.^3,9 However, in accordance with the fact that sensitivity of rods and cones is most different at long wavelengths, they consistently reported seeing red objects on dark backgrounds differently than they did before surgery.³ Because clinical color assessments failed to find any indication of color vision, we conducted a gamut of tailored tests to better define patients' descriptions. We evaluated patients' perceived lightness of different colors, color detection, and saliency, comparing their treated with their untreated eyes. Although the perceived lightness of different colors was generally similar between the eyes and matched a rod-input model, patients could detect a colored stimulus only in their treated eyes. In a search task, long response times, which were further extended with array size, suggested low saliency. We suggest that treated CNGA3-achromatopsia patients can perceive a stimulus's color attribute, although in a manner that is different and very limited compared with sighted individuals. We discuss the retinal and cortical obstacles that might explain this perceptual gap.

Keywords: CNGA3; achromatopsia; color; color blindness; monochromat; rods.