Luo Xiumei, Li Bing, Li Tao, Di Yue, Zheng Changyue, Ji Shunmei, Ma Yuanyuan, Zhu Jie, Chen Xuefeng, Zhou Xiaodong
Department of Ophthalmology, Jinshan Hospital affiliated to Fudan University, Shanghai,China.
Central Laboratory, Jinshan Hospital affiliated to Fudan University, Shanghai,China.
Mol Vis. 2017 Sep 29;23:666-679. eCollection 2017.
It is well known that the dopaminergic signaling pathway plays a pivotal role in the control of axial elongation. Much research has shown that retinal dopamine (DA) is decreased in experimental myopia, but the exact alteration in DA quantity underlying the myopia model induced by flickering light (FL) has not yet been fully elucidated. Therefore, in this study, we first attempted to prove the feasibility of the myopia model induced by FL and then to determine whether and how DA and its receptors changed in myopia induced by FL.
Forty-five 2-week-old guinea pigs were randomly divided into three groups, as follows: the control group, form-deprivation myopia (FDM) group, and FL-induced myopia (FLM) group. Animals in the control and FDM groups were raised under normal illumination, and the right eyes of the FDM group were covered with semitransparent hemispherical plastic shells serving as eye diffusers. Guinea pigs in the FLM group were raised under illumination with a duty cycle of 50% at a flash rate of 0.5 Hz. The refraction, axial length (AL), and corneal radius of curvature (CRC) were measured using streak retinoscopy, A-scan ultrasonography, and keratometry, respectively, before and after 2, 4, 6, and 8 weeks of treatment. The contents of DA, 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the retina, vitreous body, and RPE were measured at the end of the 8-week experiment using high-performance liquid chromatography (HPLC). The numbers of retinal D1 DA receptor (D1DR) and D2 DA receptor (D2DR) were evaluated via immunohistofluorescence and western blot assay.
The refraction of the FLM group became more myopic throughout the experimental period, which was mainly indicated by decreased refraction and a longer AL compared with the control group (p<0.05). The contents of DA, DOPAC, and HVA in the retina, vitreous body, and RPE of the FLM group were significantly increased, but decreased in the FDM group, compared with those of the control group (both p<0.05). Like form-deprived eyes, the expressions of retinal D1DR and D2DR in FL eyes were significantly upregulated compared with controls (p<0.05).
Myopia can be induced by 0.5-Hz FL in guinea pigs at puberty. Contrary to FDM, dopaminergic neuron activity and DA release were significantly elevated in FLM. Like in FDM, the expressions of D1DR and D2DR were upregulated in FLM. Thus, the results of our study may further demonstrate that the DA system is associated with the development of myopia.
众所周知，多巴胺能信号通路在轴向伸长的控制中起关键作用。许多研究表明，实验性近视中视网膜多巴胺（DA）减少，但由闪烁光（FL）诱导的近视模型中DA量的具体变化尚未完全阐明。因此，在本研究中，我们首先试图证明FL诱导近视模型的可行性，然后确定在FL诱导的近视中DA及其受体是否以及如何变化。
将45只2周龄豚鼠随机分为三组，如下：对照组、形觉剥夺性近视（FDM）组和FL诱导近视（FLM）组。对照组和FDM组的动物在正常光照下饲养，FDM组的右眼用半透明半球形塑料壳覆盖作为眼扩散器。FLM组的豚鼠在占空比为50%、闪光频率为0.5Hz的光照下饲养。在治疗2、4、6和8周前后，分别使用带状检影法、A超超声检查和角膜曲率计测量屈光、眼轴长度（AL）和角膜曲率半径（CRC）。在8周实验结束时，使用高效液相色谱（HPLC）测量视网膜、玻璃体和视网膜色素上皮（RPE）中DA、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）的含量。通过免疫荧光和蛋白质印迹分析评估视网膜D1 DA受体（D1DR）和D2 DA受体（D2DR）的数量。
在整个实验期间，FLM组的屈光变得更加近视，主要表现为与对照组相比屈光降低和AL延长（p<0.05）。与对照组相比，FLM组视网膜、玻璃体和RPE中DA、DOPAC和HVA的含量显著增加，但FDM组降低（均p<0.05）。与形觉剥夺眼一样，与对照组相比，FL眼视网膜中D1DR和D2DR的表达显著上调（p<0.05）。
青春期豚鼠可被0.5Hz的FL诱导近视。与FDM相反，FLM中多巴胺能神经元活性和DA释放显著升高。与FDM一样，FLM中D1DR和D2DR的表达上调。因此，我们的研究结果可能进一步证明DA系统与近视的发展有关。
