Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, 63110, USA.
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Sci Rep. 2017 May 24;7(1):2390. doi: 10.1038/s41598-017-02549-8.
Pigment regeneration is critical for the function of cone photoreceptors in bright and rapidly-changing light conditions. This process is facilitated by the recently-characterized retina visual cycle, in which Müller cells recycle spent all-trans-retinol visual chromophore back to 11-cis-retinol. This 11-cis-retinol is oxidized selectively in cones to the 11-cis-retinal used for pigment regeneration. However, the enzyme responsible for the oxidation of 11-cis-retinol remains unknown. Here, we sought to determine whether retinol dehydrogenase 10 (RDH10), upregulated in rod/cone hybrid retinas and expressed abundantly in Müller cells, is the enzyme that drives this reaction. We created mice lacking RDH10 either in cone photoreceptors, Müller cells, or the entire retina. In vivo electroretinography and transretinal recordings revealed normal cone photoresponses in all RDH10-deficient mouse lines. Notably, their cone-driven dark adaptation both in vivo and in isolated retina was unaffected, indicating that RDH10 is not required for the function of the retina visual cycle. We also generated transgenic mice expressing RDH10 ectopically in rod cells. However, rod dark adaptation was unaffected by the expression of RDH10 and transgenic rods were unable to use cis-retinol for pigment regeneration. We conclude that RDH10 is not the dominant retina 11-cis-RDH, leaving its primary function in the retina unknown.
色素再生对于锥状光感受器在明亮和快速变化的光照条件下的功能至关重要。这个过程得益于最近被描述的视网膜视觉循环，其中 Muller 细胞将消耗的全反式视黄醇视觉色素回收回 11-顺式视黄醇。这种 11-顺式视黄醇在锥体中被选择性氧化为用于色素再生的 11-顺式视黄醛。然而，负责 11-顺式视黄醇氧化的酶仍然未知。在这里，我们试图确定视黄醇脱氢酶 10（RDH10）是否是驱动此反应的酶，RDH10 在杆/锥混合视网膜中上调，并在 Muller 细胞中大量表达。我们创建了在锥体光感受器、Muller 细胞或整个视网膜中缺乏 RDH10 的小鼠。体内视网膜电图和视网膜转导记录显示所有 RDH10 缺陷型小鼠系的锥体光反应正常。值得注意的是，它们的锥体驱动的暗适应无论是在体内还是在分离的视网膜中都没有受到影响，表明 RDH10 对于视网膜视觉循环的功能不是必需的。我们还生成了在杆细胞中异位表达 RDH10 的转基因小鼠。然而，杆细胞的暗适应不受 RDH10 表达的影响，并且转基因杆细胞无法将顺式视黄醇用于色素再生。我们得出结论，RDH10 不是主要的视网膜 11-顺式-RDH，其在视网膜中的主要功能尚不清楚。
