Resting-state electroretinography reveals pathological retinal oscillations in retinitis pigmentosa mice and patients

Abstract

Abstract Retinal remodeling occurs in both retinitis pigmentosa and age-related macular degeneration. However, it is still unknown whether spared retinal circuits are also functionally altered. Functional changes have been observed in animal models of retinitis pigmentosa, including the emergence of bursting oscillatory activity in retinal ganglion cells. Yet, comparable oscillatory activity, or other functional alterations, has not been demonstrated in patients. To address this gap, here we report a non-invasive corneal neurotechnology measuring in-vivo resting-state electroretinography and analyzing its frequency content and temporal characteristics to identify biomarkers of functional remodeling. We document that retinal remodeling induces bursting oscillatory activity in-vivo in retinitis pigmentosa mouse models and translate these results to patients. Moreover, we showed in mice that bursting oscillatory activity can be pharmacologically modulated in-vivo. Furthermore, reducing this oscillatory activity increases retinal excitability to electrical stimulation. These results are crucial for a better understanding of retinal degeneration and contribute to sight restoration efforts.