Amblyopia is a developmental vision disorder that affects a substantial population (1-3%) of children worldwide. Amblyopes suffer from a broad range of visual impairments, anomalous eye movements, reduced fine motor skills, and reduced social interactions. Experiencing early ocular misalignment (strabismus) or chronic monocular defocus (anisometropia) disrupts binocular vision development and without early intervention, amblyopia is likely to develop in the affected eye. To understand how vision impairments develop in amblyopic children and how they may be effectively treated require knowing at what age and where in their visual brain major neuronal anomalies emerge. Abnormal responses in a population of neurons beyond the primary visual cortex (V1) are thought to be responsible for complex vision impairments in strabismic and anisometropic amblyopes. Unfortunately, we know almost nothing about information processing in extrastriate neurons of amblyopic primates or the dynamic developmental changes in the cortical circuitry that presumably emerge soon after experiencing anisometropia or strabismus. The visual system of amblyopes is often characterized as being `noisy'. Abnormally enhanced noise in their visual brain prevents amblyopes from reliably discriminating visual stimuli. However, the nature or the source of elevated perceptual noise is not known. The primary goal of this proposal is to learn how the noisy visual brain emerges in amblyopes. Under the current grant we have identified several factors that could potentially make the vision of amblyopes noisy (putative amblyogenic factors): interocular suppression, noisy spiking patterns (trial-to-trial fluctuations) of individual neurons strong correlations of spiking noise between multiple pairs of neurons (noise correlation), and abnormal receptive field (RF) structures (noisy `decision template'). We will create macaque models of anisometropic amblyopia by optical means. We will test their sensory capacities and evaluate gaze stability. We will explore the RF structure and the spiking noise of simultaneously recorded, multiple neurons in area V2 (V2) and area V4 (V4).
In specific aim 1, we will study the onset timing and the dynamic interactions between the previously identified amblyogenic neural factors soon after experiencing chronic monocular defocus. We will test the hypothesis that interocular suppression emerges first followed by spiking noise and/or disorganized RF structures, and that lowering binocular suppression by early intervention reduces spiking noise and the disruption of RF structures in infant V2 neurons.
In specific aim 2, we will determine whether the RF structures of V4 neurons are disorganized and whether spiking noise is abnormally elevated. The magnitude of the neuronal deficits will be compared to perceptual impairments in each monkey to explore a link between physiology and behavior. Successful completion of these projects will provide critical information necessary for forging more effective strategies for the prevention and the treatment of amblyopia in children.
Amblyopia is a leading cause of vision loss in children. Our studies are designed to understand how the visual brain of amblyopic primates is altered by early abnormal visual experience due to chronic defocus in one eye. The proposed research attempts to generate the information that will have a significant impact on the development of more effective strategies for the prevention and treatment of amblyopia in children.
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