The role of dopamine and other neuromodulators as light signals in the inner retina: a link to night blindness disorders

多巴胺和其他神经调节剂作为内视网膜光信号的作用：与夜盲症的联系

• 批准号: nhmrc : 307622
• 负责人: Dr Dario Protti
• 金额: $ 16.69万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2004
• 资助国家: 澳大利亚
• 起止时间: 2004-01-01 至 2006-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/role-dopamine-neuromodulators-blindness-disorders/99465
• 关键词: role; dopamine; other; neuromodulators; light

Although most human activities can be performed at night as efficiently as during daytime due to the use of artificial light, normal function of the circuits underlying night vision is critical. For example, when driving at night in a poorly illuminated road where the region illuminated by the headlights is processed by the cone circuit that serves daylight in the retina whilst the peripheral areas are processed by the rod driven nighttime circuit. Impairment of night vision and of the dark-light switch can have fatal consequences. Night blindness is a symptom characterised by reduced vision in the dark and slow adaptation to dim light. Some congenital night blindness disorders are caused by mutations in the photoreceptor calcium channels which mediate signal transmission. Additionally, patients treated with neuroleptics, a group of drugs which affect the dopaminergic system, suffer night vision disorders. Dopamine acts as a light signal in the retina. AII amacrine cells are pivotal neurones for night vision segregating two channels (ON and OFF) which convey visual information. AII cells are modulated by dopamine and thus, represent interesting targets to study the role of dopamine in the dark-light switch. Much is know about the action of dopamine on transmission of ON signals channelled by AII cells. However, its action on the OFF channel is largely unknown. We believe that some night vision disorders originate by imbalance in the dopaminergic system in the retina and its effects on AII cells. We will test our hypothesis by studying the modulatory effect of dopamine on calcium dependent signal transmission between AII cells and their partners in the OFF channel. Our hypothesis will be further tested by using animal models in which dopamine receptor function is altered. The results of these studies will provide us with an invaluable model to understand the physiological basis of the dark-light switch and of the role of dopamine in night vision disorders.

虽然由于使用人造光，大多数人类活动在夜间可以像白天一样有效地进行，但夜视系统的正常功能至关重要。例如，当在夜间在照明不良的道路上驾驶时，其中由前灯照明的区域由在视网膜中提供日光的锥体电路处理，而周边区域由杆驱动的夜间电路处理。夜间视力和暗光开关的受损可能会导致致命的后果。夜盲症是一种症状，其特征是在黑暗中视力下降，对昏暗光线的适应缓慢。一些先天性夜盲症是由介导信号传递的光感受器钙通道突变引起的。此外，用精神抑制剂（一组影响多巴胺能系统的药物）治疗的患者患有夜视障碍。多巴胺在视网膜中起光信号的作用。所有无长突细胞是夜视的关键神经元，分离两个通道（开和关），传达视觉信息。所有的细胞都受到多巴胺的调节，因此，代表了研究多巴胺在暗光开关中作用的有趣目标。关于多巴胺对由AII细胞传递的ON信号的作用，我们知道得很多。然而，它对OFF信道的作用在很大程度上是未知的。我们认为，一些夜间视力障碍起源于视网膜中多巴胺能系统的失衡及其对AII细胞的影响。我们将通过研究多巴胺对AII细胞及其关闭通道中伙伴之间钙依赖性信号传递的调节作用来验证我们的假设。我们的假设将通过使用多巴胺受体功能改变的动物模型进行进一步验证。这些研究的结果将为我们提供一个宝贵的模型，以了解黑暗-光线开关的生理基础和多巴胺在夜视障碍中的作用。