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Xiangtian Zhou, Furong Huang, Qiongsi Wang, Lishuai Zhang, Jia Qu; Opposing contributions by D2 receptor activation on form-deprivation myopia development in mice. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5460.
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© ARVO (1962-2015); The Authors (2016-present)
Many studies have shown that retinal dopamine is a major regulator of postnatal eye growth and myopia in animal models. In the present study, we determined the effects of the dopamine D2 receptor agonist, quinpirole, on form-deprivation myopia development (FDM ) and whether quinpirole acts at dopamine D2 receptors (D2R) to exert its effect on myopia development using D2R knockout (KO) mice.
Wild-type C57/BL6 (WT) littermates and corresponding D2R KO mice were subjected to FDM at postnatal 28-56 days of age. Both groups were intraperitoneally injected daily with either quinpirole (high dose: 10 mg/kg/day; low dose: 1 mg/kg/day) or vehicle for 4 weeks (starting from postnatal day 28). Their body weight, refraction, corneal radius of curvature and ocular axial components were measured at the end of 4-weeks of treatment.
Consistent with our recent report, D2R KO attenuated FDM development compared to WT littermates (-2.29±0.44 D in D2R KO versus -5.23±0.44 D in WT, p<0.05). In the WT mice, the high and low doses of quinpirole had opposite effects on FDM development: high dose promoted myopia development (-8.83±0.72 D in WT-high dose versus -5.23±0.44 D in WT-vehicle, p<0.05) while low dose inhibited it (-1.79±0.35 D in WT-low dose versus -5.23±0.44 D in WT-vehicle, p<0.05). Importantly, these opposing effects of quinpirole on FDM in WT mice were absent in D2R KO mice (D2R KO-high dose or D2R KO-low dose versus D2R KO-vehicle, p>0.05). In parallel with refraction changes, these opposing quinpirole effects were accompanied by changes in vitreous chamber depth and axial length that were consistent with those on FDM development. Furthermore, in the D2R KO mice, quinpirole or vehicle treatment did not alter FDM-induced elongation of vitreous chamber depth and increases in axial length.
Quinpirole has opposing dose dependent effects on FDM stemming from its interaction with D2R. As D2R is a GPCR coupled to various signaling transduction pathways mediating different responses that may oppose one another, it is conceivable that their activation by this D2 partial agonist is dose dependent. An additional possibility is that quinpirole activates presynaptic D2R autoreceptor-linked signaling, which in turn reduces extracellular space dopamine levels and attenuates dopaminergic signaling.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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