Bright Light Suppresses Form-Deprivation Myopia Development With Activation of Dopamine D1 Receptor Signaling in the ON Pathway in Retina
Bright Light Suppresses Form-Deprivation Myopia Development With Activation of Dopamine D1 Receptor Signaling in the ON Pathway in Retina
复制标题
亮光通过激活视网膜 ON 通路中的多巴胺 D1 受体信号来抑制形觉剥夺性近视的发展
DOI：
10.1167/iovs.16-20402
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发表时间：
2017-04-01
影响因子：
4.4
通讯作者：
Zhou, Xiangtian
中科院分区：
文献类型：
--
作者：
Chen, Si;Zhi, Zhina;Zhou, Xiangtian
目的。确定亮光 (BL) 激活特定视网膜神经元细胞类型中的多巴胺受体 D1 (D1R) 信号通路是否有助于抑制小鼠形觉剥夺性近视 (FDM)。方法。小鼠（3周龄）在正常光（NL：100-200勒克斯）或BL（2500-5000勒克斯）条件下饲养，有或没有形式剥夺。使用偏心红外光折射仪评估屈光变化，并使用光学相干断层扫描评估眼轴成分。每天腹腔注射 D1R 拮抗剂 SCH39166，以评估 BL 是否通过 D1R 激活介导 FDM 发育下降。视网膜神经元类型的六种不同生物标志物描绘了 D1R 表达的差异分布。 c-Fos 和磷酸化酪氨酸羟化酶 (p-TH) 免疫荧光染色分别评估 D1R 受体激活和多巴胺合成。结果。与 NL 中发生的变化相比，亮光暴露 4 周（每天 6 小时）可通过减少眼伸长和将屈光向远视方向移动来抑制 FDM 的发展。 SCH39166 注射完全逆转了 BL 对屈光和眼伸长的抑制作用。亮光增加了表达 pTH 和 c-fos 的细胞数量。 c-fos+细胞的增加主要发生在D1R+双极细胞(BC)中，尤其是D1R+ON-BC。结论。亮光会增加 ON 通路 BC 中的 D1R 活性，与 NL 中发生的相比，这与较少的近视移位和眼伸长相关。这些下降表明 ON 通路中 D1R 活性的增加有助于 BL 对小鼠 FDM 发育的抑制。
PURPOSE. To determine whether dopamine receptor D1 (D1R) signaling pathway activation by bright light (BL) in specific retinal neuronal cell types contributes to inhibiting form-deprivation myopia (FDM) in mice.METHODS. Mice (3-weeks old) were raised under either normal light (NL: 100-200 lux) or BL (2500-5000 lux) conditions with or without form deprivation. Refraction changes were evaluated with an eccentric infrared photorefractor, and ocular axial components with optical coherence tomography. The D1R antagonist, SCH39166, was intraperitoneally injected daily to evaluate if BL mediates declines in FDM development through D1R activation. Six different biomarkers of retinal neuronal types delineated differential distribution of D1R expression. c-Fos and phosphorylated tyrosine hydroxylase (p-TH) immunofluorescent staining evaluated D1R receptor activation and dopamine synthesis, respectively.RESULTS. Bright light exposure for 4 weeks (6 hours per day) inhibited FDM development by reducing ocular elongation and shifting refraction toward hyperopia compared with changes occurring in NL. SCH39166 injections completely reversed the inhibitory effects of BL on both refraction and ocular elongation. Bright light increased the number of cells expressing pTH and c-fos. Increases in c-fos+cells occurred mainly in D1R+bipolar cells (BCs), especially D1R+ON-BCs.CONCLUSIONS. Bright light increases D1R activity in the BCs of the ON pathway, which is associated with less myopic shift and ocular elongation than those occurring in NL. These declines suggest that increased D1R activity in the ON pathway contributes to the BL suppression of FDM development in mice.