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Kast B, Schori C, Grimm C

期刊名称:Experimental Eye Research


感受器 低氧


缺氧预处理可防止光感受器发生光诱导的变性,从而保持视网膜的形态和功能。虽然缺氧诱导转录因子12HIF1HIF2)是低氧反应的主要调节剂,但光感受器保护并不取决于视杆中的HIF1。在这里,我们使用视杆Hif2aHIF1a; Hif2a双基因敲除小鼠研究低氧预处理后视杆HIF2是否参与了保护。为了确定视杆上的潜在HIF2靶基因,我们通过RNA测序确定了低氧控制下的视网膜转录和特定的视杆Hif2a敲除。我们发现,光暴露后,视杆细胞不需要HIF2来增加低氧诱导的存活增加。转录分析发现了许多可能受视杆HIF2调节的基因;其中包括HTRA1TIMP3Hmox1。我们的结论是,无论HIF1HIF2均不是低氧预处理保护光感受器所必须的。我们推测,HIF转录因子可能是其它细胞生成以感光细胞旁分泌方式发挥作用的保护性因子所必需的。低氧预处理可诱导与HIF转录因子无关的视杆固有应答。

Hypoxic preconditioning protects photoreceptors against light-induced degeneration preserving retinal morphology and function. Although hypoxia inducible transcription factors 1 and 2 (HIF1, HIF2) are the main regulators of the hypoxic response, photoreceptor protection does not depend on HIF1 in rods. Here we used rod-specific Hif2a single and Hif1a;Hif2a double knockout mice to investigate the potential involvement of HIF2 in rods for protection after hypoxic preconditioning. To identify potential HIF2 target genes in rods we determined the retinal transcriptome of hypoxic control and rod-specific Hif2a knockouts by RNA sequencing. We show that rods do not need HIF2 for hypoxia-induced increased survival after light exposure. The transcriptomic analysis revealed a number of genes that are potentially regulated by HIF2 in rods; among those were Htra1, Timp3 and Hmox1, candidates that are interesting due to their connection to human degenerative diseases of the retina. We conclude that neither HIF1 nor HIF2 are required in photoreceptors for protection by hypoxic preconditioning. We hypothesize that HIF transcription factors may be needed in other cells to produce protective factors acting in a paracrine fashion on photoreceptor cells. Alternatively, hypoxic preconditioning induces a rod-intrinsic response that is independent of HIF transcription factors.


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