Amblyopia (commonly known as """"""""lazy eye"""""""" Or literally as """"""""blunt sight"""""""") is a condition in which vision in one eye is poor even though any refractive error is corrected and there is no other obvious damage to the eye. It is now widely accepted that the clinical pathology in amblyopia involves a functional weakening of connections between the visual cortex and one or both of the eyes. The condition affects about 3% of the general population and arises during childhood while the visual centers of the brain are still developing. It is an almost certain outcome of anything that causes the two eyes to see differently during infancy or early childhood, such as an uncorrected strabismus, cataract, or anisometropia. Current treatments are helpful if performed early enough, but beyond 7 or 8 years of the age the condition is untreatable. The long-term objectives of this project are l) to provide a possible route for growth factor therapy of amblyopia in adulthood, and 2) to further understand mechanisms underlying actions of nerve growth factor (NGF) in visual cortex plasticity.
0ne specific aim of this proposal is to undertake efforts to promote recovery from pre-existing amblyopia in experimental animals with NGF-treatment. Amblyopia will be induced artificially in young kittens by suturing shut the eyelid of one eye. The animals will be allowed to grow up in this situation. It is already known that this will result in the sutured eye losing functional connections with the visual cortex. 0nce these animals are past the critical period for visual cortex plasticity (at least one year of age), NGF will be infused into the visual cortex coincident with manipulations of visual inputs through the two eyes. Then ocular dominance distributions of neurons will be assessed in both NGF-treated and control visual cortices with standard single unit recordings. Another specific aim of this proposal is to investigate whether NGF-induced plasticity in adult visual cortex is mediated through the cholinergic pathway. Antagonists of cholinergic receptors will be infused with NGF, together into visual cortex of adult cats, and the effects of NGF on ocular dominance distributions of visual cortical neurons will be determined using electrophysiological recordings.
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