The proposed research seeks clarification of neural and/or biochemical mechanisms that control postnatal ocular growth and the development of myopia (nearsightedness) good experimental model, evidence of retinal participation in the regulatory process and discovery of clear neuropharmacological effects on eye growth make this a reasonable goal. In the chick, juvenile monkey and likely in man, a vision-dependent feedback mechanisms influences postnatal ocular growth, hence implicating neural mechanisms in control of eye size and refractive error. Our recent observations of elevated vasoactive intestinal peptide in the myopic monkey retina and depressed dopamine in the myopic chick retina constitute the first identifications of neurochemical alterations in experimental myopia. Our follow-up pharmacological studies demonstrate that local application of dopaminergic agents not only can prevent the axial elongation characteristic of myopia but also can modify its shape. Expanding these studies, we have found that cholinergic agents also influence the growth of the chick eye in the axial dimension. We seek a more detailed understanding of how these neurochemical and neuropharmacological observations can be integrated into an improved understanding of the mechanisms that regulate ocular growth and refractive status. Using the chick as a model, studies will be directed to the following areas: 1) Further definition of the role of dopamine in ocular growth control and the development of refractive errors. We shall seek further correlates of retinal dopamine with experimental conditions influencing eye growth and shall continue to study the influence of locally applied dopamine agents. 2) Clarification of cholinergic influences on eye growth. Besides expanding our pharmacological findings, we shall initiate biochemical and histochemical studies. 3) Identification of other mechanisms governing ocular growth and refractive error. In seeking other possible neural mechanisms, we shall emphasize the peripheral nervous system and neuropeptides. By coordinating pharmacological, biochemical, histochemical and anatomical methods, we seek to clarify mechanisms controlling ocular growth, emmetropization and the development of myopia. We hope that these studies ultimately will lead to an improved understanding of human myopia and to a viable drug therapy to prevent its development.

National Institute of Health (NIH)
National Eye Institute (NEI)
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Visual Sciences A Study Section (VISA)
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University of Pennsylvania
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