Preprint: Gene therapy restored cone signals that reached the visual cortex in four of seven children
Preprint: Gene therapy restored cone signals that reached the visual cortex in four of seven children
On October 14, the authors published a preprint on seven children with achromatopsia, a congenital condition in which retinal cones fail to transmit normal light signals from birth. After treatment in one eye, four participants showed cone signals that reached the visual cortex, the brain region that processes vision, and became available to conscious perception.
Cones support daylight vision and the ability to distinguish colors and fine details. In people with variants in CNGA3, cones remain in the retina but do not function as light-sensitive cells. Standard visual acuity tests conflate two separate questions: whether cone function has recovered and whether the brain can use the new signal.
Seven children aged 8 to 15 received gene therapy beneath the retina of their poorer-seeing eye. The researchers then showed them patterns made from pairs of colors chosen to produce identical signals in rods, the cells responsible for night vision, but different signals in cones. A child's ability to distinguish such a pattern indicates that cones are functioning. Functional MRI tracks changes in blood flow associated with brain activity. The researchers used it to check whether the visual cortex had developed a map in which the location of activity corresponded to the pattern's location in the visual field.
The authors detected such a map in four participants. It persisted across repeat sessions, and previously invisible patterns became distinguishable. Improvements on sensitivity tasks persisted for up to three years and occurred only in the treated eye. In one participant, the treated eye detected flicker at frequencies up to approximately 30 Hz, or 30 flashes per second, compared with around 4 Hz in the untreated eye.
The extent of recovery varied across visual functions. The fovea, the central part of the retina, supports vision for the finest details and contains no rods in people with achromatopsia. In most participants, visual acuity remained within the usual range of test-retest variability; only one showed a substantial improvement. One participant could distinguish colored targets from gray ones, while neither of the two participants who completed these tests developed normal color discrimination. The authors suggest that these differences reflect the possibility that rods had kept fast visual pathways active. The fovea has received no light-driven input since birth, while normal color discrimination requires separate circuits that compare signals from different cones.
The authors propose evaluating sensory gene therapy along the entire pathway: whether receptors produce a signal, whether that signal reaches the brain, and whether it helps the person distinguish visual stimuli. In this study, they compared tests that isolate cone signals, maps of visual cortex activity, and perceptual tasks. Together, these measures show where along the pathway from the retina to the brain the treatment had an effect.