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Li Qin Jiang, Keli Long, Xiangtian Zhou, Jia Qu; Reciprocal Activities of Two Type Dopamine Receptors Determine the Myopia Development. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3437.
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Dopaminergic activity has been known to involve emmetropization, a key process of the refractive development. However, the mechanism by which it regulates myopia development has not been elucidated. This study was to explore the reciprocal role of dopamine receptors (D1 that activates cAMP, and D2 that inhibits cAMP) in regulating myopia development in albino guinea pigs, which spontaneously develop myopia with reduced dopamine activity.
Albino guinea pigs were treated for 4 weeks in 2-6 weeks after birth with apomorphine (APO), an unselective dopamine receptor agonist, by semiretrobulbar injection to right eyes daily, with left eyes used as untreated controls. Six dosages of APO (7.5, 25, 75, 250, 750, and 2500 ng) were tested. Dopamine receptor D1 selective agonist SKF38393, and D2 selective agonist Quinpirole, both in 3 doses (10, 100, and 1000 ng), were also investigated, with untreated or vehicle-treated animals as controls. 15 animals were used per group for each dose. Refraction (RE) and axial length (AL) were measured at 2, 4, and 6 weeks by eccentric infrared photoretinoscopy and A-scan ultrasound, respectively. The difference of RE and AL between treated and untreated eyes was calculated at 6-week old. The negative value of RE difference and positive AL difference indicate myopia progress, and vice versa.
Albino guinea pigs showed significant myopia progress, from RE at -5.96±0.48D in 2 weeks, to -7.52±0.79D at 6 weeks, similar to the vehicle group. APO showed biphasic effects on RE and axial eye growth: a low dose (25ng) promoted myopia development with RE at -8.82±0.67D in 6 weeks, while a high dose (250ng) prevented it (RE: -5.73±0.68D at 6-week). The difference between two eyes in APO and vehicle groups were: RE: -1.16±0.33D vs. 0.09±0.25D (p<0.01), and AL: 0.04±0.01mm vs. 0.00±0.01mm (p=0.135) in APO 25ng group; while RE was +1.72±0.61D vs. 0.09±0.25D (p<0.05), and AL was -0.10±0.04mm vs. 0.00±0.01mm (p<0.05) in 250ng group. Interestingly, D1 receptor agonist SKF38393 at 100ng had a significant inhibitory effect on myopia development, with the RE difference +1.00±0.52D vs. 0.00±0.53D (p<0.05); and the AL difference is -0.06±0.03mm vs. 0.00±0.04mm (p<0.05). D2 receptor agonist quinpirole appeared to promoted myopia, but there was no statistic significance.
Our findings demonstrated that dopaminergic system regulates myopia development through the reciprocal activities of two type dopamine receptors in albino guinea pigs: D1 receptor activity inhibits, while D2 receptor agonist promotes myopia, which may have preventive or therapeutic potential in myopia development, especially in youth myopia.<!--EndFragment-->
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