Photoreceptor signaling in primate retina

灵长类动物视网膜中的感光信号传导

基本信息

批准号：
10337270
负责人：
Raunak Sinha
金额：
$ 35.56万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-03-01 至 2026-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10337270
关键词：
Address Behavioral Benchmarking Blindness Brain Cell physiology Cells Cessation of life Computer Models Cone Degenerative Disorder Disease Electrophysiology (science)Exhibits Eye Movements Foundations Frequencies GTP-Binding Proteins Generations Goals Heterogeneity Human Individual Intervention Kinetics Knowledge Light Location Macaca Macular degeneration Measurement Mediating Medical Modeling Molecular Morphology Movement Neurons Night Blindness Noise Organism Output Perception Performance Peripheral Persons Photons Photoreceptors Phototransduction Physiological Primates Process Property Prosthesis Recording of previous events Replacement Therapy Research Resolution Rest Retina Retinal Cone Retinal Degeneration Retinal Diseases Rod Signal Transduction Stimulus Testing Time Vision Visual Visual Cortex Visual Fields Visual system structure Work biological systems biophysical model density design effective therapy experience fovea centralis human stem cells improved insight interest light intensity luminance novel response retinal rods retinotopic stem cell therapy stem cells tool visual information visual stimulus

Address Behavioral Benchmarking Blindness Brain Cell physiology Cells Cessation of life Computer Models Cone Degenerative Disorder Disease Electrophysiology (science)Exhibits Eye Movements Foundations Frequencies GTP-Binding Proteins Generations Goals Heterogeneity Human Individual Intervention Kinetics Knowledge Light Location Macaca Macular degeneration Measurement Mediating Medical Modeling Molecular Morphology Movement Neurons Night Blindness Noise Organism Output Perception Performance Peripheral Persons Photons Photoreceptors Phototransduction Physiological Primates Process Property Prosthesis Recording of previous events Replacement Therapy Research Resolution Rest Retina Retinal Cone Retinal Degeneration Retinal Diseases Rod Signal Transduction Stimulus Testing Time Vision Visual Visual Cortex Visual Fields Visual system structure Work biological systems biophysical model density design effective therapy experience fovea centralis human stem cells improved insight interest light intensity luminance novel response retinal rods retinotopic stem cell therapy stem cells tool visual information visual stimulus

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项目摘要

Project Summary/Abstract Human daylight vision is dominated by signaling in the fovea, a specialization unique to diurnal primates which is responsible for half of the retinal output and hence input to the higher visual centers. Our high-definition central vision is initiated in the cone photoreceptors which are packed in a dense and exquisite pixel array in the fovea. This unique arrangement together with the specialized retinal circuitry is key for the highest spatial and chromatic resolution attributed to our central vision. It is well known that the density and morphology of cone photoreceptors differ remarkably between foveal and peripheral primate retina, but our knowledge about the physiological and functional differences remain quite poor. Interestingly, our recent observations in primate retina have revealed that the time course of cone signals in the fovea is two-fold slower than in the peripheral retina consistent with the two-fold difference in the temporal sensitivity of our cone-mediated vision to high-frequency flicker. The broad goal of our project is to determine the full breadth of heterogeneities in cone signaling, “retinotopy of function”, across a range of visual inputs and functional properties. We will focus on three salient questions across three aims: 1) What are the differences in key functional properties of signals originating in the primate cone photoreceptors across the visual field? (2) Is cellular noise generated in cone phototransduction homogenous in cones across the visual field and what limits does it pose for cone function and perception? (3) Do foveal cones exhibit differences in function during natural vision compared to cones in rest of the primate retina? We will answer these questions using electrophysiological recordings of responses from cones in primate retina and models that describe cone function. The proposed work will provide a detailed insight into primate cone signaling especially in the fovea. Death of cone photoreceptors is the primary cause for vision loss in retinal diseases that attack the fovea such as macular degeneration. A therapy option that holds promise for such degenerative diseases is stem cell derived photoreceptor replacement therapy. Our study will provide the much-needed baseline information about foveal cone signaling to evaluate cone function in human stem cell derived retina for designing effective stem cell-based therapies as a way to ultimately cure degenerative retinal diseases such as macular degeneration and others.

项目摘要/摘要人类的日光视觉由中央凹的信号传导主导，这是昼夜隐私所特有的专业负责剩余输出的一半，因此输入了较高的视觉中心。我们的高清中心视觉是在圆锥体光受体中启动的，该锥形感受器以浓密和独特的像素阵列包装在中央凹中。这种独特的布置以及专门的视网膜电路是最高空间和色彩的关键解决方案归因于我们的中心愿景。众所周知，锥形感受器的密度和形态凹foveal和周围灵长类动物视网膜之间的显着不同，但我们对生理学和功能差异仍然很差。有趣的是，我们最近对灵长类动物视网膜的观察已经揭示了中央凹中锥信号的时间过程慢了两倍我们的锥体介导的视力对高频闪烁的暂时敏感性的两倍差异。宽阔我们项目的目标是确定锥信号传导中的异质性的全部宽度，“功能视网膜”，跨各种视觉输入和功能属性。我们将重点关注三个突出问题目的：1）源自主锥体中信号的关键功能特性的差异是什么视野遍布视野？（2）是在锥形光转导中产生的细胞噪声跨视野的圆锥体以及圆锥功能和感知构成什么限制？（3）做凹锥与灵长类动物视网膜其余的锥相比，自然视力期间功能的暴露差异？我们将使用灵长类动物视网膜中锥的反应的电生理记录回答这些问题描述锥功能的模型。拟议的工作将为主锥信号传导提供详细的见解特别是在中央凹。锥形感受器的死亡是永久性疾病视力丧失的主要原因攻击fovea，例如黄斑变性。一种对这种退化有希望的疗法选择疾病是干细胞衍生的光感受器替代疗法。我们的研究将提供急需的有关凹锥信号传导的基线信息，以评估人类干细胞衍生的视网膜中的锥体功能设计有效的基于干细胞的疗法，以最终治愈退化性残留疾病，例如黄斑变性等。