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D. L. Nickla, A. T. Cheng; Atropine and Apomorphine in Emmetropization: Evidence for Inhibitory Interactions on a Common Growth Regulatory Pathway. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3848.
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In animal models, some muscarinic antagonists and dopaminergic agonists inhibit the development of myopia. It is unknown however, at what point in the signal cascade these compounds exert their effects, or if they act on the same pathway. Evidence suggests that they may have negative interactions at the retinal level (Schmid & Wildsoet; 2004). To elucidate this, we tested the effects of various muscarinic antagonists, and a combination of atropine and apomorphine, on the choroidal and axial responses to lens-induced hyperopic defocus in chicks.
One eye of 7-12 d old chicks was fitted with a -10 D lens for 4 days. Daily intravitreal injections of drug (20 ul) or saline were given. Drugs tested were atropine (n=12), pirenzepine (Prz, n=10), oxyphenonium (Oxy, n=13), dicyclomine (n=6), apomorphine (n=13), and apomorphine+atropine (n=12). High frequency A-scan ultrasonography was done before lens wear, and on day 4 prior to the injection and 3 hours later. Refractions were measured on day 4. Oxy (n=12) and Prz (n=5) were also tested on normal eyes.
As expected, both atropine and apomorphine inhibited the development of myopia (drug vs saline: -1.2 and -1.8 D vs 4.8 D) by inhibiting axial growth (254 and 288 um vs 440 um; p<0.05). However, when used in combination, they prevented the ocular growth inhibition induced by either alone (368 um vs 254 and 288 um; p<0.05 for both). Both drugs (alone) were also associated with transient increases in choroidal thickness (37 and 41 um vs -9 um; p<0.05) which were absent in the combined treatment (-12 um). Prz and Oxy, but not dicyclomine, were also effective in inhibiting axial myopia and were associated with transient choroidal responses (respectively vs saline: 81 and 88 um vs -9 um; p<0.05). Prz, Oxy and atropine significantly inhibited the "long-term" lens-induced choroidal thinning as well. Finally, in normal eyes, Prz and Oxy induced significant axial hyperopia (6.6 and 5.4 D vs 0.6 D). These also induced choroidal thickening (152 and 68 um).
All drugs that inhibited the development of myopia were associated with transient choroidal thickening, while those that were ineffective were not, strengthening a link between the two in emmetropization. The data from the combined drugs support the hypothesis that the two systems act at different sites on a common pathway, and have negative interactions, possibly at the retinal level.
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