Investigation of a new approach for treatment of deprivation-induced vision impairment

Brain regions that support visual perception complete their development early in postnatal life when visual experience informs the proper development of neurons and their connections. Disruption of normal visual experience during this formative postnatal period, as can happen with cataracts, refractive errors or misaligned eyes, alters the development of neural connections and can result in the leading cause of vision impairment in children called amblyopia. We have recently demonstrated fast and complete recovery from amblyopia in kittens reared in complete darkness for 10 days. Our preliminary investigation of the molecular changes underlying this recovery suggests that darkness reverses the accumulation of proteins called 'molecular brakes' that attenuate the capacity for neural plasticity and recovery. We have also recently observed a similar remarkable recovery from amblyopia following temporary binocular retinal inactivation. Successful treatment of amblyopia with darkness or retinal inactivation represents a potential breakthrough in visual health research. Experiments in this proposal will provide a better understanding of the optimal treatment parameters for both treatments, and will investigate potential mechanisms engaged to enable recovery. We will address key issues important for the translation of these treatments to human benefit, including examination of the time window within which they promote recovery, the consequences of different lengths of treatment, and the importance of post-treatment binocular vision. We further propose to provide a more thorough mechanistic understanding of the molecular events that enhance neural plasticity and promote visual recovery, with focus on a collection of proteins known to restrict the capacity for neural modification. The overarching goal of this proposal is build up to a proof of principle study on a clinical population of human amblyopes.