The neuroretina is protected by its own defense system, that is microglia and the complement system. Under normal physiological conditions, microglial activation is tightly regulated by the neurons although the underlying mechanism remains elusive. Using published single-cell RNA sequencing data sets, we found that immune regulatory molecules including CD200, CD47, CX3CL1, TGFβ, and complement inhibitor CD59a are expressed by various retinal neurons. Importantly, we found that photoreceptors express higher levels of CD47 and CD59a, which was further confirmed in cultured 661W cells, WERI-Rb1 cells, and microdissected photoreceptors from human eyes. The expression of CD59a mRNA in 661W cells was upregulated by TNFα and hypoxia, whereas LPS, hypoxia, and IL-4 upregulated CD47 mRNA expression in 661W cells. Immunofluorescence staining detected strong CD59a immunoreactivity in the outer nuclear layer, inner/outer segments, and discrete staining in ganglion cell layer (GCL), inner plexiform layer (IPL), and outer plexiform layer. The expression of CD59a in photoreceptors was increased in the detached retina, but decreased in retinas from experimental autoimmune uveoretinitis (EAU) mice. In EAU retina, CD59a was highly expressed by active immune cells. CD47 was detected in GCL, IPL, and inner nuclear layer and some photoreceptors. The expression of CD47 in photoreceptors was also increased in the detached retina but decreased in EAU retina. In a coculture system, 661W enhanced arginase-1 and reduced IL-6 mRNA expression in BV2 microglial cells. Our results suggest that photoreceptors express immune regulatory molecules and may have the potential to regulate immune activation in the outer retina/subretinal space under pathophysiological conditions.

中文翻译：

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视网膜免疫调节剂的单细胞 RNA 测序研究确定了光感受器中 CD47 和 CD59a 的表达 - 视网膜下免疫调节的意义。

神经视网膜受其自身的防御系统保护，即小胶质细胞和补体系统。在正常的生理条件下，小胶质细胞的激活受到神经元的严格调节，尽管潜在的机制仍然难以捉摸。使用已发表的单细胞 RNA 测序数据集，我们发现包括 CD200、CD47、CX3CL1、TGFβ 和补体抑制剂 CD59a 在内的免疫调节分子由各种视网膜神经元表达。重要的是，我们发现光感受器表达更高水平的 CD47 和 CD59a，这在培养的 661W 细胞、WERI-Rb1 细胞和来自人眼的显微切割光感受器中得到了进一步证实。661W 细胞中 CD59a mRNA 的表达被 TNFα 和缺氧上调，而 LPS、缺氧和 IL-4 上调 661W 细胞中 CD47 mRNA 的表达。免疫荧光染色检测到外核层、内/外节段中的强 CD59a 免疫反应性，以及神经节细胞层 (GCL)、内丛状层 (IPL) 和外丛状层的离散染色。CD59a 在光感受器中的表达在脱离的视网膜中增加，但在实验性自身免疫性葡萄膜炎 (EAU) 小鼠的视网膜中减少。在 EAU 视网膜中，活性免疫细胞高度表达 CD59a。在 GCL、IPL、内核层和一些光感受器中检测到 CD47。CD47 在光感受器中的表达在脱离的视网膜中也增加，但在 EAU 视网膜中减少。在共培养系统中，661W 增强了 BV2 小胶质细胞中的 arginase-1 并降低了 IL-6 mRNA 的表达。