The Role of Muller Cells in Visual Pigment Regeneration

Muller 细胞在视觉色素再生中的作用

• 批准号: 7467429
• 负责人: GABRIEL H TRAVIS
• 金额: $ 38.5万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7467429
• 关键词: Address; Biochemical; Cells; Chemicals; Chickens; Color Visions; Defect; Disease; Evaluation; Event; Eye; GRB10 gene; Genes; Hereditary Disease; Human; Inherited; Light; Mediating; Molecular; Muller' s cell; Mus; Mutation; Natural regeneration; Opsin; Perception; Photons; Photophobia; Photoreceptors; Pigments; Process; Proteins; Public Health; Relative (related person); Resolution; Retina; Retinal Cone; Retinal Pigments; Retinaldehyde; Role; Structure of retinal pigment epithelium; Vision; Visual; Vitamin A; cell type; chromophore; enzyme pathway; receptor; research study; retinal rods; retinol isomerase; small molecule

DESCRIPTION (provided by applicant): The first event in light perception is capture of a photon by an opsin visual-pigment within a photoreceptor cell of the retina. This triggers a chemical change in the retinaldehyde chromophore, a small molecule related to vitamin A contained within each opsin pigment. This can be likened to the tripping a mouse trap. Before light sensitivity can be restored to the `bleached' pigment, the retinaldehyde chromophore must be chemically regenerated, i.e., the mouse trap must be reset. This is accomplished by a multi-step enzyme pathway in the retinal pigment epithelium (RPE), a layer of cells adjacent to the retina. Mutations in the gene for almost every protein within this enzyme pathway cause some type of inherited blinding disease. This indicates the importance of the `visual cycle' to vision in humans. Over the years, evidence has accumulated that another type of cell, the Muller cell, located within the retina, also participates in the regeneration of visual chromophore. In particular, Muller cells may assist in the regeneration of chromophore destined for cone photoreceptors. Cones provide high-resolution color vision in bright light, and are critical to normal sight in humans. Almost nothing is known about how Muller cells regenerate visual chromophore, and what are the relative contributions of RPE versus Muller cells in rod-dominant species, such as humans. The current application addresses these questions using a `two-pronged' approach. One set of experiments seeks to identify each protein responsible for the vitamin A-processing activities detected in retina homogenates. Another set of experiments seeks to define the function of each vitamin A-processing protein previously identified in Muller cells. Information from these approaches should converge to yield a clear picture about the role of Muller cells in visual-pigment regeneration. PUBLIC HEALTH RELEVANCE: Light perception is mediated by visual pigments in the eye. For sustained vision, these pigments must be continuously regenerated. This project is to study the biochemical mechanisms of visual-pigment regeneration. Defects in pigment regeneration cause inherited blinding diseases. The project will help us understand how these genetic diseases arise.

描述（由申请人提供）：光感知中的第一个事件是视网膜感光细胞内的视蛋白视觉色素捕获光子。这会引发视黄醛发色团的化学变化，视黄醛发色团是一种与每种视蛋白色素中所含维生素 A 相关的小分子。这可以比喻为绊倒老鼠夹。在“漂白”色素恢复光敏感性之前，必须对视黄醛发色团进行化学再生，即必须重置捕鼠器。这是通过视网膜色素上皮 (RPE) 中的多步酶途径实现的，RPE 是邻近视网膜的一层细胞。该酶途径中几乎所有蛋白质的基因突变都会导致某种类型的遗传性致盲疾病。这表明“视觉周期”对人类视觉的重要性。多年来，越来越多的证据表明，另一种类型的细胞，即位于视网膜内的穆勒细胞，也参与视觉生色团的再生。特别是，穆勒细胞可以帮助用于视锥细胞的生色团的再生。视锥细胞在强光下提供高分辨率的色觉，对于人类的正常视力至关重要。关于 Muller 细胞如何再生视觉发色团，以及 RPE 与 Muller 细胞在视杆细胞优势物种（如人类）中的相对贡献，我们几乎一无所知。当前的申请使用“双管齐下”的方法解决这些问题。一组实验旨在鉴定视网膜匀浆中检测到的负责维生素 A 加工活性的每种蛋白质。另一组实验旨在确定先前在 Muller 细胞中发现的每种维生素 A 加工蛋白的功能。来自这些方法的信息应该汇聚起来，以清晰地了解穆勒细胞在视觉色素再生中的作用。公共卫生相关性：光感知是由眼睛中的视觉色素介导的。为了维持视力，这些色素必须不断再生。该项目旨在研究视觉色素再生的生化机制。色素再生缺陷会导致遗传性致盲疾病。该项目将帮助我们了解这些遗传疾病是如何产生的。