A blind person receives a gene therapy to restore light-sensitive cells in the eye, but their brain has never learned to process the signals those cells send. This project tackles the overlooked problem that even successful eye treatments can fail if the brain cannot interpret the new visual information. The researcher will study three distinct scenarios: brains that developed with only rod cells and must suddenly handle cone signals, infant eyes treated before their visual pathways have matured, and adult brains that lose sight suddenly then regain it through therapy. Using custom neuroimaging and behavioural tests, the team will map how the brain rewires itself before and after gene therapy. If successful, this work could transform regenerative eye treatments from merely repairing the eye to actively retraining the brain to see—potentially making therapies that currently show limited benefit far more effective. This is fundamental neuroscience with a direct clinical target: understanding neuroplasticity as the missing link between fixing the eye and restoring functional vision.
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This program investigates the mechanisms of neuroplasticity essential for sight rescue after regenerative therapy. After decades of research on revolutionary ocular therapies but only few available treatments, it is clear that the complexity of human sight rescue requires a paradigm shift. I will introduce a transformative neuroscience approach to eye research that treats sight rescue as a brain-wide process, applied to three eye conditions with promising new gene therapies. I hypothesise that we need mechanistic understanding of the distinct neuroplasticity challenges of each condition to uncover how therapies interface with the brain beyond the eye, and promote effective rehabilitation. Across three work packages, I will investigate 1) how a brain that has developed with only rod photoreceptor input can process never-experienced cone photoreceptor signals, 2) how treating retinal deterioration in infancy can rescue critical visual pathway development, 3) how the adult brain can adapt to sudden sight loss and then new therapy- induced signals. I will develop innovative neuroimaging and behavioural psychophysics technologies tailored to each disease profile, to characterise neuroplasticity before and after gene therapy, and stimulate visual processing. This will introduce ground-breaking methodologies to the field of regenerative medicine and reshape our understanding of neuroplasticity within the human brain.
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