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N. A. McBrien, S. Sahebjada, B. Arumugam, A. Chow, A. I. Jobling, A. Gentle; Role of M4 Receptor Antagonist in Control of Myopic Eye Growth. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3850.
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Antimuscarinic agents such as atropine and pirenzepine, are effective at inhibiting the progression of myopia. However, uncertainty remains as to which muscarinic receptor mediates this effect. Previous work, in avian and mammalian models of myopia, implicates the M4 receptor as a potential target. The current study used highly selective muscarinic toxins (MT) to further characterise the role of cholinergic mechanisms in the control of myopia.
Seven groups of week-old chicks (each ≥ n=5) underwent 5 days of monocular deprivation, with a translucent occluder, to induce myopia. These animals had daily intravitreal injections of MT3 (M4-selective antagonist), MT7 (M1-selective) or vehicle. Three concentrations of each antagonist were used (250nM to 10µM). A group of tree shrews (n=4) also underwent 5 days of monocular occlusion and were given daily injections of MT3 (10µM; occluded eye) and vehicle (contralateral eye). After the treatment period, retinoscopy and ultrasound were used to assess eye growth.
In chick, MT3 produced a significant, dose-dependent inhibition of myopia (treated - control eye; saline -10.1 ± 1.1D, 10µM MT3 -4.0 ± 1.5D, p<0.01). The majority of this effect was due to reduced vitreous chamber elongation (treated - control eye; saline +0.26 ± 0.04mm, 10µM MT3 +0.08 ± 0.07mm, p<0.05). In contrast, MT7 had no significant effect on the development of myopia, relative to saline control (MT7 10µM -9.5 ± 1.8D and +0.20 ± 0.06mm). In tree shrew, MT3 prevented the development of myopia, relative to the control eye (-0.8 ± 0.4D and 0.03 ± 0.02mm, p>0.05).
In the chick, which lacks an M1 receptor, the M4-selective antagonist inhibited myopia in a dose-dependent fashion, whereas the M1-selective antagonist had little effect on eye growth. In addition, the M4 antagonist prevented myopia development in tree shrew, which displays both M1 and M4 receptors. It is expected that findings from this study will confirm that muscarinic antagonists prevent myopia through action at the M4 receptor.CR: None Support: NH&MRC 454602
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