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Brittany Carr, William K Stell; Alpha2-Adrenergic Agonists Inhibit Form-Deprivation Myopia (FDM) in the Chick. Invest. Ophthalmol. Vis. Sci. 201657(12):.
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© 2017 Association for Research in Vision and Ophthalmology.
Myopia (near-sightedness due to elongation of the eye) is the most common vision defect in childhood. Its prevalence is rising rapidly world-wide, and effective remedies are urgently needed. Atropine – a muscarinic acetylcholine receptor (mAChR) antagonist – is one remedy, but its anti-myopia mechanism is unknown and concentrations required for significant clinical efficacy (lowest dose: 0.01-0.1% = 140-1400µM) can result in severe side-effects. Any drug can act non-specifically at increased concentrations, and evidence suggests that atropine can interact with α-adrenergic receptors (ADRA) at ≥ 1µM (Chang. 2005. Eur J Pharm). The role of these receptors in myopia has not been investigated; thus, we tested the hypothesis that ADRAs are involved in regulation of eye growth by intravitreal injection of two ADRA agonists into form-deprived chick eyes.
The right eyes of White Leghorn cockerels (age P7) were goggled with diffusers to induce FDM; the left eyes served as non-goggled controls. 20 µL of PBS, or ADRA agonists clonidine (Clon; 0.1, 1, 10mM) or guanfacine (Gfcn; 0.1, 1, 10mM), was injected intravitreally on days P8, P10, and P12. On day P13, refractive error (RE) and axial length (AL) were measured. Control eyes were not affected by treatments to the goggled eyes, so the interocular difference (d = treated-control) was taken as the measure of treatment effect (± SD; One-Way ANOVA).
PBS had no effect on FDM, but Clon and Gfcn controls differed significantly (respectively, dRE: -13 ± 2D vs. -16.5 ± 2D; p=0.002, n≥9; dAL: 0.4 ± 0.2mm vs 0.6 ± 0.2mm; p=0.007, n=12; 2-tailed unpaired t-test). Only the highest dose (10mM) of Clon inhibited FDM (dRE: -2.2 ± 3D; dAL: 0 ± 0.2mm; p<0.0001, n=10). All concentrations of Gfcn inhibited the dRE (0.1: -9.8 ± 5D, 1: -8.6 ± 3D, 10: -8.2 ± 3D; p<0.0004, n≥11), but only 1 & 10mM inhibited dAL (1: 0.4 ± 0.2mm, 10: 0.3 ± 0.2mm; p<0.01, n≥11).
These data show that ADRA agonists prevent FDM at concentrations similar to those used for atropine in the chick. Like atropine, Gfcn at 10-12mM inhibits induced myopia by 50%, whereas Clon inhibits it by ≥80%. These results demonstrate that ADRAs inside the eye may play an important role in regulating eye growth. Further investigations will test whether atropine prevents myopia by binding non-specifically to ADRAs in the eye. Studies such as these may lead to more effective myopia therapies in the future.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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