Xiaoying Zhu

Opposite Effects of Glucagon and Insulin on Compensation for Spectacle Lenses in Chicks

PURPOSE Chick eyes compensate for the defocus imposed by positive or negative spectacle lenses. Glucagon may signal the sign of defocus. Do insulin (or IGF-1) and glucagon act oppositely in controlling eye growth, as they do in metabolic pathways and in control of retinal neurogenesis? METHODS Chicks, wearing lenses or diffusers or neither over both eyes, were injected with glucagon, a glucagon antagonist, insulin, or IGF-1 in one eye (saline in the other eye). Alternatively, chicks without lenses received insulin plus glucagon in one eye, and either glucagon or insulin in the fellow eye. Ocular dimensions, refractive errors, and glycosaminoglycan synthesis were measured over 2 to 4 days. RESULTS Glucagon attenuated the myopic response to negative lenses or diffusers by slowing ocular elongation and thickening the choroid; in contrast, with positive lenses, it increased ocular elongation to normal levels and reduced choroidal thickening, as did a glucagon antagonist. Insulin prevented the hyperopic response to positive lenses by speeding ocular elongation and thinning the choroid. In eyes without lenses, both insulin and IGF-1 speeded, and glucagon slowed, ocular elongation, but glucagon and insulin each increased the rate of thickening of the crystalline lens. When injected together, insulin blocked choroidal thickening by glucagon, at a dose that did not, by itself, thin the choroid. CONCLUSIONS Glucagon and insulin (or IGF-1) cause generally opposite modulations of eye growth, with glucagon mostly increasing choroidal thickness and insulin mostly increasing ocular elongation. These effects are mutually inhibitory and depend on the visual input.

Ocular compensation for alternating myopic and hyperopic defocus

During development, the eye grows under visual feedback control, as shown by its compensating for defocus imposed by spectacle lenses. Under normal conditions the sign and magnitude of defocus vary with viewing distance, accommodative status and other factors. To explore how periods of myopic and hyperopic defocus are integrated over time we presented rapidly alternating episodes of myopic and hyperopic defocus by sequentially illuminating a nearby scrim and the wall beyond it to chick eyes wearing lenses that put the far point between the two surfaces. We found that equal periods of myopic and hyperopic defocus generally led to compensatory hyperopia, showing that myopic defocus had a disproportionate effect. Furthermore, the degree of hyperopia depended on the frequency of alternation: low frequencies (1 cycle/30 min) resulted in more hyperopia, whereas at high frequencies (1 cycle/s) the myopic and hyperopic defocus nearly cancelled each other. If similar temporal integration effects apply to humans, they may help explain why brief accommodation events may not influence lens-compensation and why a childs total reading time may be a poor predictor of myopic progression.

Effects of muscarinic agents on chick choroids in intact eyes and eyecups: evidence for a muscarinic mechanism in choroidal thinning

In chicks, ocular growth inhibition is associated with choroidal thickening and growth stimulation with choroidal thinning, suggesting a mechanistic link between the two responses. Because muscarinic antagonists inhibit the development of myopia in animal models by a non‐accommodative mechanism, we tested the hypothesis that agonists would stimulate eye growth and thin the choroid. We also hypothesized that the effective growth‐inhibiting antagonists would thicken the choroid.

Temporal integration of visual signals in lens compensation (a review)

Postnatal eye growth is controlled by visual signals. When wearing a positive lens that causes images to be focused in front of the retina (myopic defocus), the eye reduces its rate of ocular elongation and increases choroidal thickness to move the retina forward to meet the focal plane of the eye. When wearing a negative lens that causes images to be focused behind the retina (hyperopic defocus), the opposite happens. This review summarizes how the retina integrates the constantly changing visual signals in a non-linear fashion to guide eye growth in chicks: (1a) When myopic or hyperopic defocus is interrupted by a daily episode of normal vision, normal vision is more effective in reducing myopia caused by hyperopic defocus than in reducing hyperopia caused by myopic defocus; (1b) when the eye experiences alternating myopic and hyperopic defocus, the eye is more sensitive to myopic defocus than to hyperopic defocus and tends to develop hyperopia, even if the duration of hyperopic defocus is much longer than the duration of myopic defocus; (2) when the eye experiences brief, repeated episodes of defocus by wearing either positive or negative lenses, lens compensation depends on the frequency and duration of individual episodes of lens wear, not just the total daily duration of lens wear; and (3) further analysis of the time constants for the hypothesized internal emmetropization signals show that, while it takes approximately the same amount of time for the signals to rise and saturate during lens-wearing episodes, the decline of the signals between episodes depends strongly on the sign of defocus and the ocular component. Although most extensively studied in chicks, the nonlinear temporal integration of visual signals has been found in other animal models. These findings may help explain the complex etiology of myopia in school-aged children and suggest ways to slow down myopia progression.