Banerjee Seema, Wang Qin, Zhao Fuxin, Tang George, So Chunghim, Tse Dennis, To Chi-Ho, Feng Yun, Zhou Xiangtian, Pan Feng
Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong.
School of Optometry and Ophthalmology and Eye Hospital, Wenzhou Medical University, The State Key Laboratory of Optometry, Ophthalmology and Vision Science, Wenzhou, China.
Front Cell Neurosci. 2020 Jun 1;14:124. doi: 10.3389/fncel.2020.00124. eCollection 2020.
Myopia is a substantial public health problem worldwide. In the myopic retina, distant images are focused in front of the photoreceptors. The cells and mechanisms for retinal signaling that account either for emmetropization (i.e., normal refraction) or for refractive errors have remained elusive. Gap junctions play a key component in enhancement of signal transmission in visual pathways. AII amacrine cells (ACs), coupled by connexin36, segregate signals into ON and OFF pathways. Coupling between AII ACs is actively modulated through phosphorylation at serine 293 via dopamine in the mouse retina. In this study, form deprivation mouse myopia models were used to evaluate the expression patterns of connexin36-positive plaques (structural assay) and the state of connexin36 phosphorylation (functional assay) in AII ACs, which was green fluorescent protein-expressing in the Fam81a mouse line. Single-cell RNA sequencing showed dopaminergic synapse and gap junction pathways of AII ACs were downregulated in the myopic retina, although Gjd2 mRNA expression remained the same. Compared with the normal refractive eye, phosphorylation of connexin36 was increased in the myopic retina, but expression of connexin36 remained unchanged. This increased phosphorylation of Cx36 could indicate increased functional gap junction coupling of AII ACs in the myopic retina, a possible adaptation to adjust to the altered noisy signaling status.
近视是全球范围内一个严重的公共卫生问题。在近视视网膜中，远处图像聚焦在光感受器前方。视网膜信号传导中负责正视化（即正常屈光）或屈光不正的细胞和机制仍不清楚。缝隙连接在增强视觉通路信号传递中起关键作用。通过连接蛋白36耦合的AII无长突细胞（ACs）将信号分离到ON和OFF通路。在小鼠视网膜中，多巴胺通过丝氨酸293处的磷酸化对AII ACs之间的耦合进行主动调节。在本研究中，使用形觉剥夺性小鼠近视模型来评估在Fam81a小鼠品系中表达绿色荧光蛋白的AII ACs中连接蛋白36阳性斑块的表达模式（结构分析）和连接蛋白36磷酸化状态（功能分析）。单细胞RNA测序显示，尽管Gjd2 mRNA表达保持不变，但近视视网膜中AII ACs的多巴胺能突触和缝隙连接通路下调。与正常屈光眼相比，近视视网膜中连接蛋白36的磷酸化增加，但连接蛋白36的表达保持不变。Cx36磷酸化的增加可能表明近视视网膜中AII ACs的功能性缝隙连接耦合增加，这可能是一种适应机制，以适应改变的噪声信号状态。
