The Visual Systems Group, Abrahamson Pediatric Eye Institute, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Center for Chronobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Nat Cell Biol. 2019 Apr;21(4):420-429. doi: 10.1038/s41556-019-0301-x. Epub 2019 Apr 1.
During mouse postnatal eye development, the embryonic hyaloid vascular network regresses from the vitreous as an adaption for high-acuity vision. This process occurs with precisely controlled timing. Here, we show that opsin 5 (OPN5; also known as neuropsin)-dependent retinal light responses regulate vascular development in the postnatal eye. In Opn5-null mice, hyaloid vessels regress precociously. We demonstrate that 380-nm light stimulation via OPN5 and VGAT (the vesicular GABA/glycine transporter) in retinal ganglion cells enhances the activity of inner retinal DAT (also known as SLC6A3; a dopamine reuptake transporter) and thus suppresses vitreal dopamine. In turn, dopamine acts directly on hyaloid vascular endothelial cells to suppress the activity of vascular endothelial growth factor receptor 2 (VEGFR2) and promote hyaloid vessel regression. With OPN5 loss of function, the vitreous dopamine level is elevated and results in premature hyaloid regression. These investigations identify violet light as a developmental timing cue that, via an OPN5-dopamine pathway, regulates optic axis clearance in preparation for visual function.
在小鼠出生后的眼部发育过程中，作为适应高分辨率视觉的一种方式，胚胎玻璃体液脉管系统从玻璃体中退化。这个过程发生的时间非常精确。在这里，我们发现视蛋白 5（OPN5；也称为神经蛋白酶）依赖性视网膜光反应调节出生后眼睛的血管发育。在 Opn5 基因敲除小鼠中，玻璃体液脉管系统过早退化。我们证明，通过视网膜神经节细胞中的 OPN5 和 VGAT（囊泡 GABA/甘氨酸转运蛋白）进行的 380nm 光刺激可增强内侧视网膜 DAT（也称为 SLC6A3；多巴胺再摄取转运蛋白）的活性，从而抑制玻璃体内多巴胺。反过来，多巴胺直接作用于玻璃体液脉管内皮细胞，抑制血管内皮生长因子受体 2（VEGFR2）的活性，并促进玻璃体液脉管系统的退化。由于 OPN5 功能丧失，玻璃体内的多巴胺水平升高，导致玻璃体液脉管系统过早退化。这些研究确定了紫光作为一种发育定时线索，通过 OPN5-多巴胺途径，调节视轴清除，为视觉功能做准备。
