Retinal Control of Eye Growth and Myopia

视网膜对眼睛生长和近视的控制

• 批准号: 131-2013
• 负责人: Stell, William
• 金额: $ 1.82万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630742
• 关键词: Retinal; Control; Eye; Growth; Myopia

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.

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光照条件的适应的特定神经细胞、神经回路和化学信使，以及能够引起或预防近视的视网膜系统。我们将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防止近视。在这些主题下：1.光强度的时间调制作为移动空间模式的有效刺激。通过2-3小时的正常观看中断形式剥夺可以防止实验诱导的形式剥夺近视。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。通过M受体拮抗剂预防近视。一些M受体拮抗剂，如阿托品，可以预防鸡和哺乳动物的近视，但不可接受的副作用限制了它们在人类近视治疗中的应用。确定阿托品预防近视的特异性受体有助于开发更好的抗近视药物。视网膜时空加工和对比度辨别的机制。利用视动反射(转头跟随漂移条纹模式)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参与适应。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。