Adaptive Optics Retinal Microstimulator for Color Vision

描述（由申请人提供）：为了了解大脑如何感知颜色，有必要了解视网膜如何从入射光中产生视觉信号。众所周知，三种类型的锥状光感受器是任何颜色信号的起点。视锥细胞对光的反应被传递到视网膜神经节细胞，它们的轴突离开眼睛，向视觉丘脑提供输入，然后将信息传递给大脑的其他部分。目前，关于“侏儒”类视网膜神经节细胞的感受野的颜色结构存在较大的争议。为了显示颜色，必须比较不同类型的视锥细胞的反应。目前尚不清楚小神经节细胞是否只从单一的锥体类型接收比较输入，还是从锥体混合类型接收比较输入。在视觉系统的这一阶段，这些选项会导致不同的颜色编码方案，因此对颜色在以后的阶段被认为是如何处理的有重要的影响。因为小神经节细胞占视网膜输出信号的80%，所以弄清它们真正的信号特性是至关重要的。解决这个问题的主要障碍是无法识别和刺激活体视网膜中的单个视锥细胞。这项提议的目标是克服这些限制，开发一种视网膜微刺激器，可以在活体眼睛中可视化视锥细胞，识别它们的光谱类型，最重要的是，用彩色光源选择性地重复刺激单个视锥细胞。最先进的自适应光学技术将用于成像和跟踪锥镶嵌。该设计将包括几个会聚、共聚焦光学序列，用于多波长成像、刺激和锥光谱识别。为了验证该系统是否能像预期的那样传递刺激，并产生来自视锥细胞的波长特异性反应，将进行神经生理学实验，绘制为三色灵长类视觉丘脑单个神经元提供输入的视锥细胞场。这些实验是验证仪器刺激精度的唯一手段，并将为今后在人体中进行的任何研究提供必要的经验基础。公共卫生相关性：一种具有前所未有的光感受器特异性刺激控制的彩色视网膜微刺激器将有益于研究正常和病变光感受器功能的眼科医生和生理学家，以及那些对大脑皮层中颜色处理的神经基础感兴趣的人。该仪器将首次提供在细胞水平上探测与锥体营养不良和色盲有关的生理和知觉变化的机会。它也将有助于测试正在开发的视网膜纤毛病基因疗法的有效性。

Description (provided by applicant): To understand how the brain perceives color, it is necessary to learn how the retina creates its visual signals from the incoming flux of light. It is known that three types of cone photoreceptors are the starting point for any color signals. The cone responses to light are passaged to retinal ganglion cells, and their axons leave the eye to provide input to the visual thalamus, which in turn informs the rest of the brain. At present, there is a major controversy over the chromatic structure of the receptive fields of the "midget" class of retinal ganglion cells. To signal color, the responses of different cone types must be compared. It is uncertain if the midget ganglion cells receive comparative input from only single cone types, or from cone mixtures. The options would lead to different color coding schemes at this stage of the visual system, and thus have important consequences for how color is thought to be processed at later stages. Because the midget ganglion cells comprise about 80% of the output from the retina, it is crucial to work out their true signaling properties. The main impediments to solving this problem have been the inability to identify and stimulate individual cones in the living retina. The goal of this proposal is to overcome these limitations and develop a retinal microstimulator that can visualize the cones in a living eye, identify their spectral type, and most importantly, stimulate single cones selectively and repeatably with colored light sources. State-of-the-art adaptive optics techniques will be used to image and track the cone mosaic. The design will incorporate several convergent, confocal optical trains for multiwavelength imaging, stimulation, and cone spectral identification. To verify that the system can deliver stimuli as intended and produce wavelength-specific responses from cones, neurophysiological experiments will be conducted to map the cone fields providing input to single neurons in the visual thalamus of a trichromatic primate. These experiments are the only means of validating the stimulus precision of the instrument, and will provide the empirical foundation necessary for any future studies conducted in humans. PUBLIC HEALTH RELEVANCE: A color retinal microstimulator with unprecedented control of photoreceptor- specific stimuli will benefit ophthalmologists and physiologists studying normal and diseased photoreceptor function, as well as those interested in the neural basis of color processing in the cerebral cortex. The instrument will offer the first opportunity for probing, at a cellular level, the physiological and perceptual changes associated with cone dystrophies and colorblindness. It will also be useful for testing the effectiveness of gene therapies being developed for retinal ciliopathies.