CHOROIDAL BLOOD FLOW & RETINAL PATHOLOGY IN AGING

脉络膜血流

• 批准号: 3122428
• 负责人: MALINDA E C FITZGERALD
• 金额: $ 8.97万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 1995-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3122428
• 关键词: aging; autonomic nervous system; biological models; choroid plexus; ciliary ganglion; electron microscopy; experimental brain lesion; hypertension; light adaptations; model design /development; pigeons; retina circulation; retina degeneration; sensory receptors; ultrasound blood flow measurement; vascular endothelium permeability; vascular smooth muscle nervous control; visual photoreceptor

Loss of photoreceptors that is reflected in a decline in visual capacity occurs in aging and one particularly severe manifestation of this is age-related macular degeneration (AMD). It is clear that in both aging and AMD, changes in the outer retina are occurring; however, the primary defect or defects underlying these changes are unclear. We propose to examine the effect of aging on the choroid and its neural regulation and determine if choroidal dysfunction is correlated with retinal pathology. We will use pigeons in these studies. Pigeons exhibit many of the same age-related visual changes as humans. They are a favorable animal in which to study age-related changes in neural control of choroidal blood flow because, extensive anatomical and physiological data on the neural circuits that controls choroidal blood flow in young pigeons (less than 1 yr) is available. Four different age groups of pigeons will be used (ranging from 1 to greater than or equal to 7 yrs, corresponding to 6 to greater than or equal to 50 years of age in humans. To explore the effect of aging on the choroid we will: 1) determine if basal choroidal blood flow is progressively altered with aging, using laser Doppler techniques; 2) determine if the distribution, abundance, or ultrastructural characteristics of the choroidal and choriocapillaris vascular beds are altered with aging; and 3) determine if the permeability of normally restricted serum proteins is altered in the choriocapillaris with aging. Additional studies will investigate whether the neural regulation of choroidal blood flow is altered in aging since, blood flow in the choroid is known to be under neural control by various types of peripheral sensory and autonomic fibers that adaptively regulate the choroidal blood flow in response to retinal need. We will examine the distribution of sensory and autonomic nerve fibers in the choroid in the different aged pigeons and the morphological and functional integrity of one specific neural circuit (the suprachiasmatic (SCN) - Edinger-Westphal (EW) - ciliary ganglion (CG) circuit) that has been implicated in the light-mediated reflexive control in choroidal blood flow will also be investigated. Alteration in adaptive regulation of the choroid may occur in aging, and these alterations may underlie the observed changes in photoreceptors. Finally, we will explore the possibility that changes in choroidal blood flow are correlated with photoreceptor loss in aged pigeons by correlating the physiological and functional data obtained on each animal with its data on the photoreceptors. This will be accomplished by analysis of retina at both the light and electron microscopic level, and also using morphometric techniques to determine the number and type of photoreceptors lost or affected. These experiments will provide information on the effect choroidal changes in aging may have on retinal health, which might allow a better understanding of the drastic effects of aging on photoreceptors.

视觉能力下降所反映的光感受器的丧失 发生在衰老中，其中一个特别严重的表现是 老年黄斑变性(AMD)。很明显，在老龄化过程中 和AMD，外视网膜正在发生变化；然而，主要的 这些变化背后的缺陷或缺陷尚不清楚。我们建议 观察衰老对脉络膜及其神经调节的影响 确定脉络膜功能障碍是否与视网膜病理相关。 我们将在这些研究中使用鸽子。鸽子展示了许多相同的东西 和人类一样，与年龄相关的视觉变化。它们是一种很受欢迎的动物 以研究脉络膜血神经控制的年龄相关性变化 流动是因为，关于神经的大量解剖和生理数据 控制幼鸽脉络膜血流的回路(小于 1年)可用。将使用四个不同年龄段的鸽子 (从1到大于或等于7年，对应于6到 人类年龄大于或等于50岁的。 为了探索老化对脉络膜的影响，我们将：1)确定 基础脉络膜血流量随着年龄的增长而逐渐改变，使用 激光多普勒技术；2)确定是否分布，丰度， 脉络膜和脉络膜毛细血管的超微结构特征 血管床随年龄变化；以及3)确定是否 正常受限的血清蛋白的通透性在 脉络膜毛细血管随年龄增长。更多的研究将调查 脉络膜血流量的神经调节是否发生改变 随着年龄的增长，脉络膜中的血液流动被认为是在神经下 由各种类型的外周感觉和自主神经纤维控制 自适应调节脉络膜血流对视网膜的反应 需要。我们将检查感觉神经和自主神经的分布。 不同年龄鸽子脉络膜纤维的变化 一个特定神经回路的形态和功能完整性 视交叉上(SCN)-Edinger-Westphal(EW)-睫状神经节 (CG)，这与光介导的自反性有关 脉络膜血流的控制也将被调查。蚀变 脉络膜的适应性调节可能发生在衰老过程中，而这些 这些变化可能是观察到的光感受器变化的基础。 最后，我们将探讨脉络膜血液变化的可能性 血流与老龄鸽子的光感受器丢失相关 将在每台计算机上获得的生理和功能数据进行关联 动物的光感受器数据。这将会实现的 通过对视网膜进行光镜和电子显微镜的分析， 并使用形态测量技术来确定数量和类型 光感受器丢失或受影响。 这些实验将提供有关脉络膜影响的信息 衰老的变化可能会对视网膜健康产生影响，这可能会让 了解衰老对光感受器的剧烈影响。