Hu Shisi, Li Yaoyao, Zhang Yuanjie, Shi Ruyi, Tang Ping, Zhang Di, Kuang Xiuli, Chen Jiangfan, Qu Jia, Gao Ying
The Molecular Neuropharmacology Laboratory and the Eye-Brain Research Center, State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China.
State Key Laboratory of Ophthalmology, Optometry and Visual Science, Wenzhou Medical University, Wenzhou, China.
Front Pharmacol. 2022 Dec 16;13:1082997. doi: 10.3389/fphar.2022.1082997. eCollection 2022.
Adenosine A receptors (ARs) appear early in the retina during postnatal development, but the roles of the ARs in the morphogenesis of distinct types of retinal ganglion cells (RGCs) during postnatal development and neonatal inflammatory response remain undetermined. As the RGCs are rather heterogeneous in morphology and functions in the retina, here we resorted to the Thy1-YFPH transgenic mice and three-dimensional (3D) neuron reconstruction to investigate how ARs regulate the morphogenesis of three morphologically distinct types of RGCs (namely Type I, II, III) during postnatal development and neonatal inflammation. We found that the AR antagonist KW6002 did not change the proportion of the three RGC types during retinal development, but exerted a bidirectional effect on dendritic complexity of Type I and III RGCs and cell type-specifically altered their morphologies with decreased dendrite density of Type I, decreased the dendritic field area of Type II and III, increased dendrite density of Type III RGCs. Moreover, under neonatal inflammation condition, KW6002 specifically increased the proportion of Type I RGCs with enhanced the dendrite surface area and volume and the proportion of Type II RGCs with enlarged the soma area and perimeter. Thus, ARs exert distinct control of RGC morphologies to cell type-specifically fine-tune the RGC dendrites during normal development but to mainly suppress RGC soma and dendrite volume under neonatal inflammation.
腺苷 A 受体（ARs）在出生后视网膜发育早期就已出现，但 ARs 在出生后发育过程中不同类型视网膜神经节细胞（RGCs）形态发生以及新生儿炎症反应中的作用仍未明确。由于视网膜中的 RGCs 在形态和功能上相当异质，在此我们借助 Thy1-YFPH 转基因小鼠和三维（3D）神经元重建技术，来研究 ARs 在出生后发育和新生儿炎症期间如何调节三种形态上不同类型的 RGCs（即 I 型、II 型、III 型）的形态发生。我们发现，AR 拮抗剂 KW6002 在视网膜发育过程中并未改变这三种 RGC 类型的比例，但对 I 型和 III 型 RGCs 的树突复杂性产生双向影响，并特异性地改变其形态，I 型树突密度降低，II 型和 III 型树突野面积减小，III 型 RGCs 树突密度增加。此外，在新生儿炎症条件下，KW6002 特异性增加了 I 型 RGCs 的比例，其树突表面积和体积增大，同时增加了 II 型 RGCs 的比例，其胞体面积和周长增大。因此，ARs 在正常发育过程中对 RGC 形态发挥不同的控制作用，以细胞类型特异性方式微调 RGC 树突，但在新生儿炎症期间主要抑制 RGC 胞体和树突体积。
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