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Baskar Arumugam, Neville A. McBrien; Spiperone Prevents M1 Muscarinic Antagonist Inhibition of Myopia in Tree shrew. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3431. doi: https://doi.org/.
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The D2 antagonist spiperone was recently demonstrated to prevent M4 muscarinic antagonist inhibition of myopia in chicks. The present study investigated the influence of spiperone on the inhibition of myopia by the highly selective M1 muscarinic antagonist, MT7, in the tree shrew model.
Tree shrews underwent monocular form-deprivation (MD) to induce myopia. Tree shrews were randomly placed in one of four groups (n=5 each group); Group 1 - MD + MT7 (220nM); Group 2 - MD + MT7(220nM) + Spiperone (110nM); Group 3 - MD + Spiperone (110nM); Group 4 - MD only. All drugs were applied via intravitreal injection in a volume of 7 µl. The control eye of each animal received daily intravitreal injections of vehicle (7 µl) and remained unoccluded. Refractive and structural measurements were taken before and after the treatment period using streak retinoscopy and A-scan ultrasonography respectively.
The D2 antagonist Spiperone was found to prevent M1 muscarinic antagonist inhibition of myopia (Treated - Control eye; MD+Spiperone+MT7 = -7.8 ± 0.9 D vs MD+MT7 = -0.7 ± 0.4D; p<0.05) and did so by preventing the axial elongation of the vitreous chamber (Treated - Control eye; MD+Spiperone+MT7 = 0.13 ± 0.02mm vs MD+MT7 = 0.01 ± 0.02mm; p<0.05). Spiperone treatment alone had no significant effect on experimentally-induced myopia when compared to spiperone+MT7 injections (Treated - control eye; MD+Spiperone Rx -6.3 ± 0.9D, VCD 0.08 ± 0.02mm). Histological examination of retina, choroid and sclera demonstrated no gross signs of drug induced toxicity to tissues.
Antagonism of the dopaminergic D2 receptor by spiperone prevented M1 muscarinic receptor antagonist (MT7) inhibition of experimentally-induced myopia in tree shrew. These findings implicate dopaminergic signalling in the muscarinic antagonist control of myopia.
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