摘要目的:应用多巴胺D4受体(D4R)激动剂PD-168077和拮抗剂L-745870观察D4R在正常屈光发育以及形觉剥夺性近视(FDM)小鼠中的作用.方法:实验研究.将168只4周龄C57BL/6小鼠分为正常屈光发育组和FDM组(单眼剥夺,对侧眼为对照),每组又分为溶剂组和药物组(D4R激动剂PD-168077:1 mg/kg和10 mg/kg;D4R拮抗剂L-745870:1 mg/kg和10 mg/kg),所有动物给予2周的正常视觉环境或持续形觉剥夺及每日腹腔注射溶剂或药物,其中,正常屈光发育组在5周龄时给予视网膜电图(ERG)检测.所有动物均在实验前后测量屈光度、眼轴和角膜前表面曲率半径等生物学参数.采用配对t检验、单因素方差分析、重复测量方差分析对数据进行分析.结果:D4R激动剂PD-168077不影响正常屈光发育小鼠的屈光发育,而D4R拮抗剂L-745870只有在10 mg/kg时才促进正常小鼠往远视方向漂移(P=0.047),但不影响眼轴等生物学参数.10 mg/kg PD-168077在刺激强度为-0.699 log cd·s·m-2时升高了暗视ERG的OPs振幅(P=0.04),而L-745870对暗视、明视ERG的a波、b波和OPs波振幅均无明显影响.PD-168077促进FDM小鼠的近视进展(P=0.004),并伴随着玻璃体腔深度和眼轴的延长;L-745870可以抑制FDM小鼠的近视进展(P＜0.001),同时抑制了玻璃体腔深度和眼轴的延长.前房深度、晶状体厚度、角膜曲率半径等参数不受实验因素的影响.结论:D4R受激动或拮抗对正常屈光发育小鼠的屈光发育无明显作用;但D4R受激动能促进FDM小鼠的近视进展而D4R受拮抗能抑制近视进展,提示D4R受抑制能减缓FDM小鼠的近视进展.

abstractsObjective:To investigate the role of dopamine D4 receptor (D4R) in the development of normal refraction and form-deprivation myopia (FDM) by applying D4R agonist PD-168077 and D4R antagonist L-745870 in mice.Methods:This was an animal experimental study.Four-week-old C57BL/6 mice were raised either in a visually normal environment or subjected to FDM by covering one eye with vision obstructing goggles while the other eye served as the normal control.Both groups were divided into sub-groups including vehicle and drug groups (D4R agonist PD-168077:1 mg/kg/day and 10 mg/kg/day;D4R antagonist L-745870:1 mg/kg/day and 10 mg/kg/day).They were intraperitoneally injected daily for two weeks.ERG was measured in normal enviroment mice on postnatal day 35.Refraction,corneal curvature radius,and ocular axial components were measured in all animals prior to and after each experiment.Statistical analyses were performed by a paired t test,one-way ANOVA,and repeated measurement ANOVA.Results:Normal refractive development was not affected by D4R agonist PD-168077 treatment.On the other hand,the D4R antagonist L-745870 enhanced normal refractive development towards hyperopia at a dose of 10 mg/kg (P=0.047) with no significant changes in other biometric parameters.PD-168077 increased the ERG OPs amplitude under scotopic conditions at an intensity of-0.699 log cd·s·m2 (P=0.04),while L-745870 had no significant effect on the a-wave,b-wave,or summed OPs amplitudes under scotopic and photopic conditions.The development of FDM was promoted by PD-168077 treatment (P=0.004),with increases in both vitreous chamber depth and axial length.In contrast,D4R antagonist L-745870,inhibited FDM (P＜0.001),with a shortened vitreous chamber depth and axial length.No significant changes in anterior chamber depth,lens thickness or corneal curvature radius were observed.Conclusions:D4R is activated or inactivated had no significant effects on normal refractive development in mice.In contrast,in a form-deprived environment,D4R is activated enhance while D4R inactivated inhibit FDM development,suggesting D4R activation enhances while D4R inactivation inhibits the development of myopia in mice.