Abstract
Abstract
Gene therapy can restore retinal signals absent since birth in animal models, yet the translation to humans remains challenging. An unresolved possibility is that meaningful retinal rescue already occurs in humans, but its impact is masked by downstream neural bottlenecks shaped by long-term deprivation. Tracing restored signals through the visual system is therefore essential to distinguish rescue and constraints.
We address this challenge in
CNGA3
-associated achromatopsia, in which retinal cone photoreceptors are present but non-functional from birth. We used tests specifically targeting cone-mediated processing to trace signals from genetically modified cones from the retina to visual cortex and perception.
After treatment in late childhood, we find clear evidence of new cone signals reaching visual cortex in 4 out of 7 patients. These signals were replicable over years, retinotopically organised, available for conscious perception and showed higher temporal resolution. Recovery of foveal acuity and canonical colour vision remained limited, consistent with neuroplasticity constraints on specialised neurocircuitry beyond critical developmental windows.
Together, these findings show that the human brain can incorporate a new sensory signal after years of complete congenital deprivation, while revealing selective bottlenecks that limit full visual recovery. They provide a framework for optimising sensory restoration: measure rescued input, trace downstream integration of signal, and tailor treatment timing and rehabilitation to maximise functional gain.