Retinal Control of Eye Growth and Myopia

眼睛和视觉对生存至关重要，适应不断变化的环境对于感知形态、对比和运动至关重要。我们研究的长期目标是确定特定的神经细胞、神经回路和化学信使参与视网膜适应不断变化的光照条件，并确定视网膜系统可以引起或预防近视。在这些主题下，我们将测试光适应激活视网膜网络和利用递质多巴胺（DA），一氧化氮（NO）和乙酰胆碱（ACh）的功能途径，以及这些途径共同作用以调节眼睛生长和预防近视的想法。光强度的时间调制作为移动空间模式的有效刺激。视形剥夺中断正常观看2-3小时，可防止实验性引起的“视形剥夺”近视。我们预测，这是由于有纹理的图像在视网膜上移动时光线的闪烁造成的，而视网膜的关键通路是通过DA、NO或ACh受体来预防近视的。毒蕈碱乙酰胆碱受体拮抗剂预防近视的研究。一些毒蕈碱拮抗剂，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使用。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。时空加工和对比辨别的视网膜机制。利用视动力学反射（头部转动遵循漂移条纹模式）和形式剥夺性近视的诱导/预防作为视网膜回路功能的指标，我们将确定DA、NO和ACh如何促进视网膜回路的适应。由此产生的发现将揭示在大多数脊椎动物（包括人类）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.