Hemiretinal form deprivation: evidence for local control of eye growth and refractive development in infant monkeys.

Many aspects of ocular growth and refractive development are regulated by visual feedback associated with the eye’s refractive state (see refs 1 and 2 for reviews). Knowledge of the operational properties of the vision-dependent mechanisms that influence refractive development is critical for understanding the role of vision in the genesis of common refractive errors and for developing the optimal treatment regimens for refractive error. In this respect, one of the most important discoveries arising from animal research is that in some species many of the effects of vision on ocular growth and refractive development appear to be mediated by mechanisms that are located entirely within the eye (see refs 2 and 3 for reviews). The primary evidence for these retinal mechanisms has come from reduction-strategy experiments that have examined the effects of a visual stimulus on refractive development when the obvious neural inputs and/or outputs from the eye have been eliminated. For example, in chicks and tree shrews pharmacological blockade and/or surgical section of the optic nerve do not interfere with the phenomenon of form-deprivation myopia (FDM)4–6 or the recovery from FDM7 and although the set point for emmetropization is altered by optic nerve section, compensation for positive and negative lenses still occurs.8,9 Similarly, surgical interruption of the primary parasympathetic inputs to the eye does not prevent FDM or lens induced changes in refractive error in chicks.9 These experiments show that the visual signals that alter eye growth do not have to leave the eye and that the most obvious neural input to the eye is not essential for many aspects of vision-dependent ocular growth. In addition, it has been shown that these retinal mechanisms exert their influence in a spatially restricted, local manner. The most direct evidence for the local nature of these retinal mechanisms come from experiments in which the nature of visual experience has been varied across the visual field. For example, in chicks, tree shrews and guinea pigs that are reared with diffusers or negative lenses that only cover part of the visual field, the axial elongation and myopia are restricted to the affected part of the retina (McFadden, IOVS, 2002, 43, E-Abstract 189).10–14 Similarly, in chicks positive lenses that only affect the image over half the retina slow vitreous chamber elongation and produce hyperopia only in the treated portion of the retina.10 These results demonstrate that the ocular mechanisms that regulate eye growth pool visual signals from restricted spatial regions and exert their influence locally. It is thought that the actions of these local retinal mechanisms alter the shape of the eye in response to variations in the environment in order to enhance the optimum focus across the retina.1,13,15,16 It is not known if local retinal mechanisms are involved in emmetropizing responses in primates. In a study involving a small number of monkeys, Raviola and Wiesel17 found that optic nerve section prevented FDM in stumptail macaques, but not in rhesus monkeys. In addition, surgically eliminating the parasympathetic and sympathetic inputs to the eye did not prevent FDM in rhesus monkeys.17 These results suggest that there are vision-dependent retinal mechanisms in rhesus monkeys that influence eye growth, but not in stumptail monkeys. This discrepancy between two closely related species is puzzling and may have come about as a result of the variability associated with the phenomenon of form-deprivation myopia in monkeys,18–21 possible hyperopic shifts produced by optic nerve section,9 and/or the small number of animals studied. Regardless, it has not been clearly established that refractive development is mediated by retinal mechanisms in primates and there have not been any previous attempts to characterize the spatial summation properties of any potential retinal mechanisms in primates. Because of the significance of local retinal mechanisms to our understanding of the effects of vision on refractive development, it is critical to determine if they exist in primates and if they can produce predictable changes in eye shape. The great majority of what we know about local retinal mechanisms comes from studies in chicks. However, because of differences in the structure of the sclera in chicks and primates,3 it is not reasonable to expect that similar visual manipulations will produce comparable shape changes in chicks and primates. For example, the cartilaginous portion of the chick sclera is comparatively rigid and depriving half of the retina of a chick produces a prominent bulge on the deprived side of the eye.5,13 Because primates have a less rigid fibrous sclera, it is possible that providing half of the retina with a stimulus for growth would produce a more symmetrical, prolate axial elongation in primates. In this study, we employed a rearing strategy that has provided strong evidence for the existence of local retinal mechanisms in chicks, guinea pigs, and tree shrews. Specifically, we examined the effects of hemi-retinal form deprivation on ocular growth and the pattern of peripheral refraction in infant monkeys. Some of these results have been presented in abstract form.22