Activation of Dopamine D2 Receptor Is Critical for the Development of Form-Deprivation Myopia in the C57BL/6 Mouse
Activation of Dopamine D2 Receptor Is Critical for the Development of Form-Deprivation Myopia in the C57BL/6 Mouse
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DOI：
10.1167/iovs.13-13211
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发表时间：
2014-09-01
影响因子：
4.4
通讯作者：
Zhou, Xiangtian
中科院分区：
文献类型：
--
作者：
Huang, Furong;Yan, Tingting;Zhou, Xiangtian
目的。本研究使用多巴胺 D2 受体 (D2R) 敲除 (KO) 小鼠来研究 D2R 活性在形觉剥夺性近视 (FDM) 发展中的作用。将 D2R 拮抗剂舒必利全身给药于野生型 (WT) 小鼠，以验证 D2R 在 FDM 发展中的参与。方法。对 D2R KO 和 WT C57BL/6 小鼠进行 FDM。野生型小鼠每天腹腔注射舒必利，剂量为8μg/g体重，持续4周。在实验的第4周测量体重、屈光度、角膜曲率半径和眼轴分量。对实验组与对照组各眼部参数的差异进行统计学比较。结果。与 WT 同窝小鼠相比，D2R KO 小鼠 (FD-KO) 的形觉剥夺性近视显着降低（眼间差异，FD-KO 小鼠为 -2.12 +/- 0.91 屈光度 [D]，FD-WT 为 -5.35 +/- 0.83 D，P = 0.014），玻璃体腔深度更小（0.008 +/- 0.006 对比 0.014）。 0.026 +/- 0.006 毫米，P = 0.044）和轴向长度（-0.001 +/- 0.007 与 0.027 +/- 0.008 毫米，P = 0.007）。此外，与用载体治疗的动物相比，用舒必利治疗的动物的 FDM 减弱（FD-舒必利为 -2.01 +/- 0.31 D，FD-DMSO 为 -4.06 +/- 0.30 D，P < 0.001），玻璃体腔深度生长延迟（-0.001 +/- 0.006 对比 0.022 +/- 0.004 毫米，P = 0.003）和轴向长度（-0.004 +/- 0.007 与 0.027 +/- 0.005 毫米，P = 0.001）。结论。 D2R 的遗传和药理学失活会减弱小鼠 FDM 的发育，表明作用于 D2R 的多巴胺似乎促进 C57BL/6 小鼠 FDM 的发育。需要进一步研究使用选择性阻断视网膜 D2R 的动物模型来证实这些结果。
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.