Activation Of Dopamine D2 Receptor Is Critical For The Development Of Form-Deprivation Myopia In The C57bl/6 Mouse
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE(2014)
Abstract
PURPOSE. This study used dopamine D2 receptor (D2R) knockout (KO) mice to investigate the role of D2R activity in the development of form-deprivation myopia (FDM). Sulpiride, a D2R antagonist, was administered systemically into wild-type (WT) mice to validate the involvement of D2R in FDM development.METHODS. The D2R KO and WT C57BL/6 mice were subjected to FDM. Wild-type mice received daily intraperitoneal injections of sulpiride, 8 mu g/g body weight, for a period of 4 weeks. The body weight, refraction, corneal radius of curvature, and ocular axial components were measured at week 4 of the experiment. Differences in all ocular parameters between the experimental and control groups were compared statistically.RESULTS. Form-deprivation myopia in D2R KO mice (FD-KO) was significantly reduced compared with their WT littermates (interocular difference, -2.12 +/- 0.91 diopter [D] in FD-KO versus -5.35 +/- 0.83 D in FD-WT, P = 0.014), with a smaller vitreous chamber depth (0.008 +/- 0.006 vs. 0.026 +/- 0.006 mm, P = 0.044) and axial length (-0.001 +/- 0.007 vs. 0.027 +/- 0.008 mm, P = 0.007). Furthermore, FDM was attenuated in animals treated with sulpiride (-2.01 +/- 0.31 D in FD-sulpiride versus -4.06 +/- 0.30 D in FD-DMSO, P < 0.001) compared with those treated with vehicle, with a retardation in growth of vitreous chamber depth (-0.001 +/- 0.006 vs. 0.022 +/- 0.004 mm, P = 0.003) and axial length (-0.004 +/- 0.007 vs. 0.027 +/- 0.005 mm, P = 0.001).CONCLUSIONS. Genetic and pharmacological inactivation of D2R attenuates FDM development in mice, suggesting that dopamine acting on D2R appears to promote the development of FDM in C57BL/6 mice. Further studies are required to confirm these results using animal models in which retinal D2R is selectively blocked.
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Key words
myopia, dopamine D2 receptor, mice, gene knockout
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