Insights into the mechanism of atropine's anti-myopia effects: evidence against cholinergic hyperactivity and modulation of dopamine release.

BACKGROUND AND PURPOSE The ability of the muscarinic-cholinergic antagonist atropine to inhibit myopia development in humans and animal models would suggest that cholinergic hyperactivity may underlie myopic growth. To test this, we investigated whether cholinergic agonists accelerate ocular growth rates in chickens. Furthermore, we investigated whether atropine alters ocular growth by down-stream modulation of dopamine levels, a mechanism postulated to underly its anti-myopic effects. EXPERIMENTAL APPROACH Muscarinic (muscarine and pilocarpine), nicotinic (nicotine), and non-specific (oxotremorine and carbachol) cholinergic agonists were administered to chicks developing form-deprivation myopia (FDM) or chicks that were otherwise untreated. Vitreal levels of dopamine and its primary metabolite (3,4-dihydroxyphenylacetic acid (DOPAC)) were examined using mass spectrometry in form-deprived chicks treated with atropine (360, 15 or 0.15nmoles). Further, we investigated whether dopamine antagonists block atropine's anti-myopic effects. KEY RESULTS Unexpectedly, administration of each cholinergic agonist inhibited FDM (p<0.05) but did not affect normal ocular development (p=0.165). Atropine only affected dopamine (p<0.05) and DOPAC (p<0.05) levels at its highest dose. Dopamine antagonism did not alter atropine's anti-myopia effects (p=0.478). CONCLUSIONS AND IMPLICATIONS Muscarinic, nicotinic, and non-specific cholinergic agonists inhibited FDM development. This indicates that cholinergic hyperactivity does not underly myopic growth and questions whether atropine inhibits myopia via cholinergic antagonism. We also report that changes in retinal dopamine release are not required for atropine's anti-myopic effects. Finally, nicotinic agonists may represent a novel and more targeted approach for the cholinergic control of myopia as they are unlikely to suffer from the anterior segment side-effects associated with muscarinic treatment.