Alpha2-adrenoceptor agonists inhibit form-deprivation myopia in the chick

Background The putative myopia-controlling receptor is thought to be muscarinic acetylcholine receptor subtype M-4, because mamba toxin-3 can inhibit form-deprivation myopia in chicks at a far lower concentration than atropine. However, mamba toxin-3 is equally potent at the human alpha(1A)-, alpha(1D)-, and alpha(2A)-adrenoceptors. To test the hypothesis that alpha-adrenoceptors might be involved in regulation of eye growth, the treatment effects of alpha(2)-adrenoceptor agonists brimonidine, clonidine, and guanfacine, and antagonist yohimbine, on form-deprivation myopia in the chick were measured. Methods Right eyes of White Leghorn chicks were goggled with diffusers to induce form-deprivation myopia; left eyes were left open as controls. Goggled eyes were injected intravitreally with 20 mu L of vehicle, or 2, 20, or 200 nmol of brimonidine, clonidine, guanfacine, or yohimbine, 24, 72, and 120 hours after goggle application. Alternatively, myopia was inhibited physiologically by goggle removal for two hours, and the alpha(2)-adrenoceptor antagonist, yohimbine, was injected to test whether it could block this type of myopia inhibition. One day after the last injection, refractive error and axial length were measured. Results Brimonidine (20 and 200 nmol) and clonidine (200 nmol) effectively inhibited experimentally induced increases in negative refractive error and axial elongation. All doses of guanfacine significantly inhibited induced negative refractive error, but only 20 and 200 nmol significantly inhibited axial elongation. Yohimbine had no effect on form-deprivation myopia, but 200 nmol reduced the myopia-inhibiting effect of goggle removal. Conclusion High concentrations of alpha(2)-adrenoceptor agonists, similar to those required by atropine, inhibited chick form-deprivation myopia; antagonism by yohimbine had no effect. High-concentration yohimbine partially interfered with emmetropisation in form-deprived chicks experiencing normal vision for two hours per day. These data support the hypothesis that treatment with high concentrations of adrenergic drugs can affect experimentally induced myopia and normal visual processes.