Animal Models of Experimental Myopia: Limitations and Synergies with Studies on Human Myopia

Abstract

Form-deprivation myopia (FDM) is induced in eyes occluded with translucent diffusers; lens-induced myopia (LIM) when negative lenses are fitted over the eye, imposing hyperopic defocus. Hyperopically defocused images accelerate axial elongation, whereas myopic defocus slows axial elongation, driving refractions towards emmetropia. In contrast, human refractive development aims for a refraction close to +1 D, where normal visual acuity can be achieved with accommodation until later in life. However, environments with strong educational pressures and limited time outdoors accelerate axial elongation, inducing myopic shifts in refraction that decline with age, with little evidence of mechanisms maintaining emmetropia. There is little evidence that natural myopic defocus slows human myopia progression, but, paradoxically, myopic defocus imposed with specialised lenses slows myopia progression. Both FDM and LIM rapidly depress retinal dopamine release and downregulate the immediate early gene Egr-1. Children who spend more time outdoors are protected from myopia, probably due to exposure to brighter light and increased dopamine release outdoors, since bright light and dopamine agonists suppress experimental myopia. Atropine acts on similar pathways, which may also be involved in genetic forms of myopia involving outer retinal mutations that could affect the ON-bipolar pathway and reduce dopamine release.