Laboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952, Zurich, Switzerland.
Zurich Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
Sci Rep. 2021 Aug 17;11(1):16666. doi: 10.1038/s41598-021-96150-9.
Oxygen delivery to the retinal pigment epithelium and the outer retina is essential for metabolism, function, and survival of photoreceptors. Chronically reduced oxygen supply leads to retinal pathologies in patients and causes age-dependent retinal degeneration in mice. Hypoxia can result from decreased levels of inspired oxygen (normobaric hypoxia) or reduced barometric pressure (hypobaric hypoxia). Since the response of retinal cells to chronic normobaric or hypobaric hypoxia is mostly unknown, we examined the effect of six hypoxic conditions on the retinal transcriptome and photoreceptor morphology. Mice were exposed to short- and long-term normobaric hypoxia at 400 m or hypobaric hypoxia at 3450 m above sea level. Longitudinal studies over 11 weeks in normobaric hypoxia revealed four classes of genes that adapted differentially to the hypoxic condition. Seventeen genes were specifically regulated in hypobaric hypoxia and may affect the structural integrity of the retina, resulting in the shortening of photoreceptor segment length detected in various hypoxic groups. This study shows that retinal cells have the capacity to adapt to long-term hypoxia and that consequences of hypobaric hypoxia differ from those of normobaric hypoxia. Our datasets can be used as references to validate and compare retinal disease models associated with hypoxia.
向视网膜色素上皮和外视网膜输送氧气对于光感受器的代谢、功能和存活至关重要。慢性供氧不足会导致患者的视网膜病变，并导致小鼠出现年龄相关性视网膜变性。缺氧可能是由于吸入氧气水平降低（常压缺氧）或气压降低（低压缺氧）引起的。由于视网膜细胞对慢性常压或低压缺氧的反应大多未知，我们研究了六种缺氧条件对视网膜转录组和光感受器形态的影响。将小鼠暴露于海拔 400 米的短期和长期常压缺氧或海拔 3450 米的低压缺氧环境中。在常压缺氧中进行的为期 11 周的纵向研究揭示了适应不同缺氧条件的四类基因。17 个基因在低压缺氧中受到特异性调控，可能影响视网膜的结构完整性，导致在各种缺氧组中检测到光感受器节段长度缩短。这项研究表明，视网膜细胞有能力适应长期缺氧，并且低压缺氧的后果与常压缺氧不同。我们的数据集可用于验证和比较与缺氧相关的视网膜疾病模型。
