Dr. Mark Bear, PhD
PiCower Professor of Neuroscience, MIT
Monday, April 23, 2018
12pm - 1pm
489 Minor Hall
Mobilizing synaptic plasticity to promote recovery from amblyopia
Amblyopia is a prevalent form of visual disability that arises during infancy and early childhood when inputs to the visual cortex from the two eyes are poorly balanced (e.g., by misalignment of the eyes, asymmetric refraction, or opacities and obstructions of one eye). Characteristics of amblyopia are very poor acuity in one eye, and an attendant loss of stereopsis. The current standard of care is to promote recovery of the weak amblyopic eye by temporarily patching the fellow eye. However, the effectiveness of this procedure is limited by poor compliance, a reduction of vision in the patched eye, and variable outcomes that typically do not include recovery of binocularity. Additionally, the procedure is ineffective if it is initiated after age 10. The need for improved treatments for amblyopia is widely acknowledged.
Animal studies over the past 50 years have uncovered the pathophysiology of amblyopia. It is well documented that temporary monocular deprivation (MD) alters the strength of synapses in primary visual cortex (V1) that renders cortical neurons unresponsive to stimulation of the deprived eye. We now have a detailed understanding of how synapses are weakened when an animal is deprived of vision in one eye. During MD, well-correlated retinal cell activity is replaced by “noise” which, via weak NMDA receptor activation, drives the internalization of AMPA receptors at thalamocortical synapses in V1. During reverse occlusion (patch therapy), these weakened synapses can regain strength. Studies of how patch therapy might enable the long-term potentiation of weak and ineffective synapses have suggested novel approaches to promote recovery of function with advantages over the current standard of care.