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B. Arumugam, N. McBrien; The D2 Antagonist Spiperone Prevents Muscarinic Antagonist Control of Experimentally-Induced Myopia in Chick. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1195.
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The broadband muscarinic antagonist atropine has been demonstrated to effectively inhibit the axial elongation of the vitreous chamber in both animal models of myopia and in human myopia. Recently the use of highly selective muscarinic antagonists MT-3 (M4 antagonist) and MT-7 (M1 antagonist) have both been found to inhibit axial myopia in a mammalian model of myopia. The present study investigated the influence of the D2 antagonist spiperone on muscarinic antagonist inhibition of myopia.
One week-old chicks underwent four days of monocular form-deprivation, to induce myopia. Chicks were randomly placed in one of four groups (n=8) receiving daily intravitreal injections of either; Group 1- Spiperone (180 nM, D2-selective antagonist); Group 2-MT3 (90nM) + Spiperone (180nM); Group 3-MT3 (90 nM); Group 4-Vehicle. Following the treatment period, refractive and structural measurements were assessed at the beginning of the fifth day.
The D2 antagonist Spiperone, by itself, had no significant effect on the level of induced myopia when compared to the vehicle injection group, in either induced myopia (Treated - Control eye; Spiperone -11.5 ± 0.8 D vs Vehicle -11.7 ± 2.3D, p>0.05) or in axial elongation of the vitreous chamber (Treated - Control eye; Spiperone 0.40 ± 0.04mm vs Vehicle 0.35 ± 0.09mm, p>0.05). When Spiperone was co-injected with MT3, the inhibitory effect of MT3 alone on experimentally-induced myopia was prevented (Treated - Control eye; MT3 + Spiperone Rx -11.2 ± 1.2D, VCD +0.37 ± 0.03mm vs MT3 Rx -4.7 ± 1.2D, VCD +0.04 ± 0.05mm, p<0.05). Histological examination of retina, choroid and sclera demonstrated no gross signs of drug induced toxicity to tissues.
The addition of the dopaminergic D2 antagonist, spiperone, reduced the effectiveness of the M4 muscarinic antagonist MT3 inhibition of experimentally-induced myopia. These findings implicate the involvement of the dopaminergic system in muscarinic antagonist inhibition of myopia.
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