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Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews.

ABSTRACT: We examined the effect of intravitreal injections of D1-like and D2-like dopamine receptor agonists and antagonists and D4 receptor drugs on form-deprivation myopia (FDM) in tree shrews, mammals closely related to primates. In eleven groups (n = 7 per group), we measured the amount of FDM produced by monocular form deprivation (FD) over an 11-day treatment period. The untreated fellow eye served as a control. Animals also received daily 5 µL intravitreal injections in the FD eye. The reference group received 0.85% NaCl vehicle. Four groups received a higher, or lower, dose of a D1-like receptor agonist (SKF38393) or antagonist (SCH23390). Four groups received a higher, or lower, dose of a D2-like receptor agonist (quinpirole) or antagonist (spiperone). Two groups received the D4 receptor agonist (PD168077) or antagonist (PD168568). Refractions were measured daily; axial component dimensions were measured on day 1 (before treatment) and day 12. We found that in groups receiving the D1-like receptor agonist or antagonist, the development of FDM and altered ocular component dimensions did not differ from the NaCl group. Groups receiving the D2-like receptor agonist or antagonist at the higher dose developed significantly less FDM and had shorter vitreous chambers than the NaCl group. The D4 receptor agonist, but not the antagonist, was nearly as effective as the D2-like agonist in reducing FDM. Thus, using intravitreally-administered agents, we did not find evidence supporting a role for the D1-like receptor pathway in reducing FDM in tree shrews. The reduction of FDM by the dopamine D2-like agonist supported a role for the D2-like receptor pathway in the control of FDM. The reduction of FDM by the D4 receptor agonist, but not the D4 antagonist, suggests an important role for activation of the dopamine D4 receptor in the control of axial elongation and refractive development.

SUBMITTER: Ward AH

PROVIDER: S-EPMC5567805 | biostudies-other | 2017 Jan

REPOSITORIES: biostudies-other

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Project description:BACKGROUND:The putative myopia-controlling receptor is thought to be muscarinic acetylcholine receptor subtype M4 , 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 α1A -, α1D -, and α2A -adrenoceptors. To test the hypothesis that α-adrenoceptors might be involved in regulation of eye growth, the treatment effects of α2 -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 μL 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 α2 -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 α2 -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.

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Intravitreally-administered dopamine D2-like (and D4), but not D1-like, receptor agonists reduce form-deprivation myopia in tree shrews.

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