Muller Cell Domains in the Retina

视网膜中的米勒细胞域

• 批准号: 6958449
• 负责人: DAVID A DILORETO
• 金额: $ 18.01万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6958449
• 关键词: Adenoviridae; Muller' s cell; acid base balance; astrocytes; biological signal transduction; calcium flux; cell cell interaction; cell morphology; cell population study; confocal scanning microscopy; developmental neurobiology; gliosis; green fluorescent proteins; laboratory rat; neurons; neuropathology; organ culture; photostimulus; retina circulation; retina degeneration; tissue /cell culture; transfection /expression vector; visual photoreceptor

DESCRIPTION (provided by applicant): Defining Muller cell domains and the effect that their breakdown has on the retina is an entirely new approach to studying retinal degenerations. Defining an anatomic Muller cell domain has implications for each cell that it contacts, while the functionality of the domain has implications for the Muller cell's role as an active regulator of neuronal processing. If the Muller cell's domain is compromised during degeneration, this could result in aberrant glial and neuronal signaling, insufficient delivery of substrates and/or less efficient removal of waste products, which would ultimately contribute to neuronal degeneration. My goal in this proposal is to test the hypotheses that: (1) the Muller cell forms distinct anatomical domains; (2) domains have functional significance; and (3) breakdown of domains during degeneration contributes to neuronal dysfunction. To label individual Muller cells in vivo, intravitreal injections of adenovirus; will be used to deliver enhanced green fluorescent protein to the Muller cell. Confocal microscopy will be used to image the Muller cell and identify its domain within the retina. Once the domain is anatomically defined, calcium imaging studies will be performed via the caging and uncaging of calcium within Muller cells. Calcium signaling in adjacent Muller cells as well as photoreceptor cells will be measured. Changes in light-evoked photoreceptor cell responses within the Muller cell domain as well as pH will be measured and compared to changes outside the domain. Finally, a model of retinal degeneration will be used to test the above effects in Muller cells that have become reactive or gliotic. The role the Muller cell plays in health and in disease will be determined based on domain structure within the retina. How this affects photoreceptor cell function will also studied. Thus, establishing the central role that the Muller cell plays in retinal health and disease may provide a potential target for new clinical therapies that might delay or prevent neuronal loss and help to preserve vision.

描述（由申请人提供）：定义 Muller 细胞域及其分解对视网膜的影响是研究视网膜变性的全新方法。定义解剖学穆勒细胞结构域对其接触的每个细胞都有影响，而该结构域的功能则对穆勒细胞作为神经元处理的主动调节器的作用具有影响。如果 Muller 细胞的结构域在变性过程中受到损害，这可能会导致神经胶质和神经元信号传导异常、底物输送不足和/或废物清除效率较低，这最终将导致神经元变性。我在这个提案中的目标是测试以下假设：（1）穆勒细胞形成不同的解剖结构域； (2) 域名具有功能意义； (3)退化过程中结构域的分解导致神经元功能障碍。体内标记单个 Muller 细胞，玻璃体内注射腺病毒；将用于将增强的绿色荧光蛋白递送至穆勒细胞。共焦显微镜将用于对 Muller 细胞进行成像并识别其在视网膜内的区域。一旦在解剖学上定义了该区域，就可以通过 Muller 细胞内钙的囚禁和解禁来进行钙成像研究。将测量邻近米勒细胞以及感光细胞中的钙信号传导。将测量 Muller 细胞域内光诱发感光细胞反应以及 pH 值的变化，并将其与域外的变化进行比较。最后，视网膜变性模型将用于测试已变得反应性或神经胶质增生的米勒细胞中的上述效果。穆勒细胞在健康和疾病中所发挥的作用将取决于视网膜内的域结构。还将研究这如何影响感光细胞功能。因此，确定 Muller 细胞在视网膜健康和疾病中发挥的核心作用可能为新的临床疗法提供潜在的目标，这些疗法可能会延迟或防止神经元损失并有助于保护视力。