This project seeks to contribute to the understanding of the etiology of myopia, a leading cause of blindness, by studying the severe myopia produced by deprivation of form vision in chickens. This animal model has three important features: the visual deprivation of one part of the retina produces myopia of only that part of the eye, and the scleral growth can be modulated up or down as necessary to compensate for myopia or hyperopia, suggesting that the eye can sense its refractive error and compensate for it. This has important implications in understanding how the eye grows and how it can go awry in clinical myopia.Three sets of experiments are proposed: (i) To study the cellular basis of myopia and emmetropization, the bidirectional modulation of scleral growth will be investigated in an in vitro system as assessed by incorporation of radiolabeled sulfur into in organ cultures and in dissociated cell cultures. The increase in proteoglycan synthesis in myopic scleras and cells of myopic eyes, and the decrease in those of recovering eyes will be studied to determine whether the modulation is achieved via a growth factor continuously or transiently released. Conditioned medium experiments will investigate the experiments will investigate the roles of he retinal pigment epithelium, choroid and retina as sources of relevant growth factors. Finally, different known growth factors will be added to the cultures to determine their effect on scleral growth in vitro. (ii) By in vivo studies, evidence will be sought that the recognized role of dopamine in the amelioration in form deprivation myopia represents a specific inhibition of the deprivation effect by using agonists on partially occluded eyes.In addition, scleras of tree shrews, which provide a mammalian model for myopia, will be studied to determine whether the myopia in these animals is also largely due to enhanced growth of the posterior sclera. (iii) The nature of the emmetropization process will be explored with experiments directed at determining the roles of the choroid and sclera in compensating for myopia or hyperopia.
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