Retinal Control of Eye Growth and Myopia

眼睛和视力是生存的关键，而适应不断变化的条件对于感知形状、对比度和运动是必不可少的。我们研究的长期目标是确定参与视网膜对不断变化的照明条件的适应的特定神经细胞、神经回路和化学信使，并确定可导致或预防近视的视网膜系统。 我们将在以下主题下测试光适应利用多巴胺(DA)、一氧化氮(NO)和乙酰胆碱(ACh)递质激活视网膜网络和功能通路的想法，以及这些通路共同作用于调节眼睛生长和预防近视的想法： 1.光强的时间调制作为移动空间图案的有效刺激。 中断形觉剥夺2-3小时的正常观看可以防止实验诱导的“形觉剥夺”近视。我们预测，这是由于光线闪烁，因为纹理图像在视网膜上移动，关键的视网膜通路通过DA、NO或ACh受体防止近视。 2.M受体拮抗剂对近视的预防作用 一些M受体拮抗剂，如阿托品，可以预防小鸡和哺乳动物的近视，但不可接受的副作用限制了它们对人类近视的治疗作用。确定阿托品预防近视的特异性受体将有助于开发更好的抗近视药物。 3.视网膜时空加工和对比度辨别机制。 使用视动反射(转头遵循漂移条纹模式)和形觉剥夺性近视的诱导/预防作为视网膜回路功能的指标，我们将确定DA、NO和ACh如何在视网膜回路中促进适应。 由此产生的发现将揭示在包括人类在内的大多数脊椎动物物种的视网膜中起作用的基本视觉机制，并可能产生治疗近视的新方法。

The eye and vision are critical to survival, and adaptation to changing conditions is essential for sensing form, contrast, and movement. The long-term goals of our studies are to identify the specific nerve cells, neural circuits, and chemical messengers involved in retinal adaptation to changing lighting conditions, and to identify the retinal systems that can cause or prevent myopia. We will test the idea that light-adaptation activates retinal networks and functional pathways utilizing the transmitters dopamine (DA), nitric oxide (NO), and acetylcholine (ACh), and that these pathways act together to regulate ocular growth and prevent myopia, under these themes: 1. Temporal modulation of light intensity as the effective stimulus for moving spatial patterns. Interruption of form-deprivation by 2-3 hrs of normal viewing prevents experimentally induced "form-deprivation" myopia. We predict that this is due to flickering of light, as textured images move across the retina, and that the key retinal pathways prevent myopia via DA, NO, or ACh receptors. 2. Prevention of myopia by antagonists to muscarinic acetylcholine receptors (mAChR). Some muscarinic antagonists, such as atropine, prevent myopia in chicks and mammals, but unacceptable side-effects limit their therapeutic use for human myopia. Identifying the specific receptor through which atropine prevents myopia will be helpful in the development of better anti-myopia drugs. 3. Retinal mechanisms of spatiotemporal processing and contrast discrimination. Using the optokinetic reflex (head-turning to follow a drifting stripe pattern) and the induction/prevention of form-deprivation myopia as indicators of retinal circuit function, we will determine how DA, NO, and ACh contribute to adaptation in retinal circuits. The resulting discoveries will reveal basic visual mechanisms that are at work in the retinas of most vertebrate species, including those of humans, and may yield new therapies for myopia.