The Visual Systems Group, Abrahamson Pediatric Eye Institute, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
Nature. 2013 Feb 14;494(7436):243-6. doi: 10.1038/nature11823. Epub 2013 Jan 16.
Vascular patterning is critical for organ function. In the eye, there is simultaneous regression of embryonic hyaloid vasculature (important to clear the optical path) and formation of the retinal vasculature (important for the high metabolic demands of retinal neurons). These events occur postnatally in the mouse. Here we have identified a light-response pathway that regulates both processes. We show that when mice are mutated in the gene (Opn4) for the atypical opsin melanopsin, or are dark-reared from late gestation, the hyaloid vessels are persistent at 8 days post-partum and the retinal vasculature overgrows. We provide evidence that these vascular anomalies are explained by a light-response pathway that suppresses retinal neuron number, limits hypoxia and, as a consequence, holds local expression of vascular endothelial growth factor (VEGFA) in check. We also show that the light response for this pathway occurs in late gestation at about embryonic day 16 and requires the photopigment in the fetus and not the mother. Measurements show that visceral cavity photon flux is probably sufficient to activate melanopsin-expressing retinal ganglion cells in the mouse fetus. These data thus show that light--the stimulus for function of the mature eye--is also critical in preparing the eye for vision by regulating retinal neuron number and initiating a series of events that ultimately pattern the ocular blood vessels.
血管模式对于器官功能至关重要。在眼睛中，胚胎玻璃血管（对于清除光学路径很重要）同时退化，视网膜血管形成（对于视网膜神经元的高代谢需求很重要）。这些事件在出生后在小鼠中发生。在这里，我们已经确定了一种调节这两个过程的光反应途径。我们表明，当小鼠的基因（Opn4）发生突变，导致非典型视蛋白黑素细胞色素缺失，或者从妊娠后期开始在黑暗中饲养时，玻璃血管在产后 8 天仍持续存在，并且视网膜血管过度生长。我们提供的证据表明，这些血管异常是由一种光反应途径解释的，该途径抑制视网膜神经元数量，限制缺氧，从而抑制血管内皮生长因子（VEGFA）的局部表达。我们还表明，该途径的光反应发生在妊娠晚期，约在胚胎第 16 天，并且需要胎儿中的光色素，而不是母亲的光色素。测量表明，内脏腔光子通量可能足以激活小鼠胎儿中表达黑素细胞色素的视网膜神经节细胞。因此，这些数据表明，光——成熟眼睛功能的刺激——对于通过调节视网膜神经元数量和启动一系列最终使眼部血管形成模式的事件来为视力做好眼睛准备也至关重要。
