Genes and visual pigments of red-green color vision

红绿色视觉的基因和视觉色素

• 批准号: 8234042
• 负责人: MAUREEN E NEITZ
• 金额: $ 52.92万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8234042
• 关键词: Acids; Animal Model; Area; Bathing; Biological; Biological Models; Cells; Circadian Rhythms; Color Visions; Electrophysiology (science); Electroretinography; Esthesia; Evolution; Functional Magnetic Resonance Imaging; Ganglia; Gene Mutation; Generations; Genes; Genetic; Goals; Grant; Human; Investments; Knock-out; Light; Lighting; Mammals; Measures; Mutation; Pathway interactions; Patients; Perception; Photophobia; Photoreceptors; Physiological; Physiology; Primates; Process; Property; Redness; Retina; Retinal; Retinal Cone; Retinal Pigments; Role; Signal Transduction; Staging; Stem cells; System; Technology; Therapeutic; Vision; Vision Disorders; Visual; Visual Pathways; Visual Psychophysics; Visual system structure; Work; blind; comparative; ganglion cell; gene therapy; interdisciplinary approach; koniocellular; melanopsin; neural circuit; public health relevance; response; retinal prosthesis; retinal rods; transmission process; visual information; visual process; visual processing

DESCRIPTION (provided by applicant): A huge investment is being made to develop treatments to restore or provide light sensitivity to the retinas of the blind. Technological advancements in several areas including stem cells, gene therapy, and retinal prostheses show great promise; however, understanding of the basic circuitry for daylight vision lags behind technology to restore light sensitivity. Exciting technological advances reinvigorate the need to understand the circuitry of visual pathways in order to identify the best light-sensitivity-restoring therapeutic strategies and the most effective implementations of them. A complete understanding of the details of the circuitry for processing visual information will bring a wealth of opportunities for developing sophisticated strategies for treating blinding vision disorders. This application focuses on a unique sub system within the primate visual system where there are exceptional opportunities to discover the workings of neural circuitry responsible for specific percepts. It is widely accepted that S-cone input to S-cone bipolar cells and in turn to small bistratified ganglion cells--the so called "S-ON/koniocellular pathway"-- is the important circuit for blue-yellow color vision; however, the fact that the spectral response properties of small bistratified ganglion cells measured physiologically do not match those of the blue-yellow opponent channel measured perceptually is an unresolved problem for the idea that the small bistratified ganglion is the biological substrate blue perception. There is less information about retinal S-OFF ganglion cells. For the only S-OFF ganglion cells that have been characterized anatomically and physiologically in primate, bath application of the ON-pathway blocker 2-amino- 4-phosphonobutyric acid (AP-4) completely blocks the S-OFF light response, suggesting that both ON and OFF S-cone signals are transmitted to the inner retina via the ON S-cone bipolar cell and that a sign inversion of the ON signal in the inner retinal circuitry is critical for generating the S-OFF response. Thus, in much the same way that rod bipolar cells provide the substrate for both ON and OFF ganglion cell responses, the ON S- cone bipolar cells appear to provide the first stage for a complete S-cone system with both ON and OFF components. Gene mutations in humans have been discovered that completely interrupt the direct transmission of signals between S-cones and the S-cone bipolar cells. These patients offer an unprecedented opportunity to study the role of the S-ON/S-OFF/koniocellular pathways in perception. Specific Aim 1: To study the role of the S-ON/S-OFF/koniocellular pathways in perception through the study of human patients with mutations that block them, using the electroretinogram, functional magnetic resonance imaging and visual psychophysics. Specific Aim 2: To isolate and study specific components of chromatic pathways in animal models using electrophysiology, physiology, and functional magnetic resonance imaging to explore how higher levels of visual processing extract usable information from the light sensitive photoreceptors. PUBLIC HEALTH RELEVANCE: Technological advancements in stem cells, gene therapy, and retinal prostheses show great promise for restoring or providing new light sensitivity to retinas of the blind; however, understanding of the basic circuitry for daylight vision lags behind the technology to provide light sensitivity. Exciting technological advances reinvigorate the need to understand the circuitry of visual pathways in order to identify the best therapeutic strategies and the most effective implementations of them. A complete understanding of the details of the circuitry for processing visual information will bring a wealth of opportunities for developing sophisticated strategies for treating blinding vision disorders. The major objective of this grant is to provide a new understanding of the circuitry responsible for a specific visual capacity--blue-yellow color vision.

描述(由申请人提供)：正在进行一项巨大的投资来开发治疗方法，以恢复盲人的视网膜或为其提供光敏感性。干细胞、基因治疗和视网膜假体等几个领域的技术进步显示出巨大的希望；然而，对日光视觉基本电路的了解落后于恢复光敏感度的技术。令人兴奋的技术进步重新激发了理解视觉通路电路的需要，以便确定最佳的恢复光敏感的治疗策略和最有效的实施方案。完全了解处理视觉信息的电路的细节将为开发治疗失明视力障碍的复杂策略带来大量机会。这项应用专注于灵长类视觉系统中的一个独特的子系统，在那里有特殊的机会发现负责特定感知的神经回路的工作原理。人们普遍认为，S神经元传入S锥双极细胞，进而进入小的双层神经节细胞--即所谓的“S通路”--是蓝黄颜色视觉的重要回路；然而，生理测量的小双层神经节细胞的光谱响应特性与感知测量的蓝黄对立通道的光谱响应特性不匹配，这是一个悬而未决的问题，因为认为小的双层神经节是蓝感知的生物底物。关于视网膜S样神经节细胞的研究较少。对于唯一具有解剖学和生理学特征的灵长类动物的S-Off神经节细胞，应用通路阻滞剂2-氨基-4-磷酸丁酸(AP-4)可完全阻断S-OFF的光反应，这表明开和离S视锥的信号都是通过On S视锥双极细胞传递到视网膜内的，视网膜内回路中ON信号的符号反转是产生S-OFF反应的关键。因此，与视杆双极细胞为ON和OFF神经节细胞反应提供底物的方式大致相同，ON S锥双极细胞似乎为具有ON和OFF成分的完整S锥系统提供了第一阶段。在人类中发现的基因突变完全中断了S锥体和S锥体双极细胞之间的信号直接传递。这些患者提供了一个前所未有的机会来研究S-开/S-关/角质形成细胞通路在知觉中的作用。具体目标1：利用视网膜电信号、功能磁共振成像和视觉心理物理学，通过对携带基因突变的人类患者的研究，研究S-开/S-关/角质形成细胞通路在知觉中的作用。具体目标2：利用电生理学、生理学和功能磁共振成像技术分离和研究动物模型中颜色通路的特定成分，以探索更高水平的视觉处理如何从光敏感的光感受器中提取有用信息。 与公共健康相关：干细胞、基因治疗和视网膜假体的技术进步显示出恢复或为盲人视网膜提供新的光敏感度的巨大希望；然而，对日光视觉基本电路的了解落后于提供光敏度的技术。令人兴奋的技术进步重新激发了理解视觉通路回路的需要，以便确定最佳治疗策略和最有效的实施方案。完全了解处理视觉信息的电路的细节将为开发治疗失明视力障碍的复杂策略带来大量机会。这笔赠款的主要目的是提供对负责特定视觉能力的电路--蓝-黄色视觉--的新理解。