The Role of Sphingosine-1-Phosphate Receptor 2 in Mouse Retina Light Responses.

The Role of Sphingosine-1-Phosphate Receptor 2 in Mouse Retina Light Responses.
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DOI:
10.3390/biom13121691
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发表时间:
2023-11-23
期刊:
影响因子:
5.5
通讯作者:
--
中科院分区:
生物学2区
文献类型:
--
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具有生物活性的鞘脂鞘氨醇-1-磷酸(S1 P)作为G蛋白偶联的S1 P受体(S1 PR 1 -5)家族的配体参与多种信号传导途径。然而,它们在神经视网膜中的具体作用仍不清楚。我们以前表明,S1 P受体亚型2(S1 PR 2)在小鼠视网膜中表达,主要是在光感受器和双极细胞,其表达被视网膜应激改变。本研究旨在阐明S1 PR 2在小鼠视网膜中的作用。我们研究了光反应视网膜电图(ERG),光学相干断层扫描(OCT)的结构差异,免疫组织化学(IHC)在野生型(WT)和S1 PR 2基因敲除(KO)小鼠在不同年龄之间的3和6个月。我们发现,在闪光强度分别为400~2000和4~2000 cd.s/m2时,S1 PR 2 KO小鼠的a波和b波反应显著增加。通过OCT,S1 PR 2 KO小鼠相对于WT还表现出视网膜神经纤维层(RNFL)和外网状层(OPL)厚度显著增加。最后,在S1 PR 2 KO小鼠中,我们通过免疫组织化学(IHC)和定量逆转录聚合酶链反应(RT-qPCR)观察到突触标记物的差异标记。这些结果表明S1 PR 2在视网膜的结构和突触组织中的特定参与,以及在光介导的视网膜功能中的潜在作用。
The bioactive sphingolipid sphingosine-1-phosphate (S1P) acts as a ligand for a family of G protein-coupled S1P receptors (S1PR1-5) to participate in a variety of signaling pathways. However, their specific roles in the neural retina remain unclear. We previously showed that S1P receptor subtype 2 (S1PR2) is expressed in murine retinas, primarily in photoreceptors and bipolar cells, and its expression is altered by retinal stress. This study aims to elucidate the role of S1PR2 in the mouse retina. We examined light responses by electroretinography (ERG), structural differences by optical coherence tomography (OCT), and protein levels by immunohistochemistry (IHC) in wild-type (WT) and S1PR2 knockout (KO) mice at various ages between 3 and 6 months. We found that a- and b-wave responses significantly increased at flash intensities between 400~2000 and 4~2000 cd.s/m2, respectively, in S1PR2 KO mice relative to those of WT controls at baseline. S1PR2 KO mice also exhibited significantly increased retinal nerve fiber layer (RNFL) and outer plexiform layer (OPL) thickness by OCT relative to the WT. Finally, in S1PR2 KO mice, we observed differential labeling of synaptic markers by immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (RT-qPCR). These results suggest a specific involvement of S1PR2 in the structure and synaptic organization of the retina and a potential role in light-mediated functioning of the retina.
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