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通量中产生视觉信号。已知三种类型的视锥光感受器是任何颜色信号的起点。视锥细胞对光的反应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，视觉丘脑反过来又通知大脑的其他部分。目前，对视网膜神经节细胞“侏儒”类感受野的颜色结构存在较大争议。为了传递颜色信号，必须比较不同视锥细胞类型的反应。这是不确定的，如果侏儒神经节细胞接收比较输入，只有单一的锥类型，或锥混合物。这些选项将导致视觉系统在这个阶段的不同颜色编码方案，从而对后期如何处理颜色产生重要影响。由于侏儒神经节细胞约占视网膜输出的80%，因此确定其真正的信号特性至关重要。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。该提案的目标是克服这些限制，并开发一种视网膜微刺激器，该微刺激器可以在活体眼睛中可视化视锥细胞，识别其光谱类型，最重要的是，用彩色光源选择性地和可重复地刺激单个视锥细胞。国家的最先进的自适应光学技术将用于图像和跟踪锥马赛克。该设计将包括几个收敛，共焦光学列车的多波长成像，刺激和锥光谱识别。为了验证该系统可以提供预期的刺激，并产生特定波长的反应，从锥，神经生理学实验将进行映射的锥场提供输入到一个三色灵长类动物的视觉丘脑中的单个神经元。这些实验是验证仪器的刺激精度的唯一手段，并将为未来在人类中进行的任何研究提供必要的经验基础。 公共卫生相关性：一个彩色视网膜微刺激器与前所未有的控制感光细胞特异性刺激将有利于眼科医生和生理学家研究正常和患病的感光功能，以及那些感兴趣的神经基础的颜色处理在大脑皮层。该仪器将首次提供在细胞水平上探测与视锥细胞营养不良和色盲相关的生理和感知变化的机会。它也将是有用的测试基因疗法的有效性正在开发的视网膜睫状体病。

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.