Establishing a New Model for Amblyopia - Amblyopia is the leading cause of poor vision in infants and children. It arises because of abnormal visual experience early in life, during a critical window of development. Leading causes for the disruption of normal visual development are strabismus (misalignment of the visual axes between the eyes), anisometropia (mismatch in refractive error between the eyes) and deprivation (physical obstruction of one or both eyes). Clinically, amblyopia is diagnosed as reduced visual acuity in one eye that is not due to physical reasons and cannot be corrected optically. Consequently, much attention has been paid to amblyopic changes in early visual stages like the primary visual cortex (V1), and to development of treatments that can correct the loss of spatial vision (most prominently patching the weak, amblyopic eye), However, there are also deficits in higher visual functions localized outside of V1. The extent of these deficits, especially at the neural level, remains poorly understood, and even less is known about whether amblyopia treatments can overcome deficits in higher visual functions. The overarching goal of this project is to establish the ferret as a new animal model for studying amblyopia from the perspective of higher visual processing. Ferrets have a complex visual system with established similarities to the primate. This includes our recent demonstration that ferret PMLS functions as a higher visual area specialized for complex motion functions like motion integration, similar to primate MT. At the same time, larger cohorts of ferrets can be tested than is possible in primates, important for a disorder that can be quite variable in its depth between subjects, and is even more variable in the outcome of treatments. To establish ferrets as an amblyopia model, the work proposed here focuses on solving two problems. First, Aim 1 establishes a robust protocol for inducing amblyopia in ferrets. To mimic the human condition as closely as possible, we plan to trigger amblyopia by generating anisometropia early in life through a lens mounted in front of one eye. Second, Aim 2 will focus on establishing chronic recordings from flexible polymer probes to support longitudinal tracking of neural changes during amblyopia treatments. Together, these Aims will generate an experimental platform for future improvements of amblyopia treatments in human patients.
