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

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.

项目概要/摘要人类的日光视觉主要由中央凹的信号控制，这是昼间灵长类动物特有的专门功能，负责一半的视网膜输出，从而输入到我们的高清中枢。视觉是在锥体感光器中启动的，这些感光器聚集在中央凹中密集而精致的像素阵列中。这种独特的布置与专门的视网膜电路一起是获得最高空间和色彩的关键众所周知，视锥细胞的密度和形态决定了我们的中心视觉。中心凹和周边灵长类视网膜之间存在显着差异，但我们对生理和边缘的了解我们最近对灵长类动物视网膜的观察表明，功能差异仍然相当小。中央凹中锥体信号的时间进程比周边视网膜慢两倍，这与我们的视锥细胞介导的视觉对高频闪烁的时间敏感性有两倍的差异。我们项目的目标是确定视锥细胞信号传导的全面异质性，“功能视网膜定位”，我们将重点关注三个方面的三个突出问题。目标：1）源自灵长类视锥细胞的信号的关键功能特性有何差异 (2) 锥体光转导中产生的细胞噪声是否均匀 (3) 做中央凹锥体与灵长类视网膜其他部分的视锥细胞相比，在自然视觉过程中表现出功能差异？使用灵长类动物视网膜中视锥细胞反应的电生理记录来回答这些问题描述视锥细胞功能的模型将提供对灵长类视锥细胞信号传导的详细了解。尤其是在中央凹，视锥细胞的死亡是视网膜疾病导致视力丧失的主要原因。攻击黄斑变性等黄斑变性的治疗方案有望治疗此类退行性病变。我们的研究将提供急需的干细胞衍生光感受器替代疗法。有关中央凹锥体信号传导的基线信息，用于评估人类干细胞来源的视网膜中的锥体功能设计有效的基于干细胞的疗法作为最终治愈退行性视网膜疾病的方法，例如黄斑变性等。