MECHANISMS 0F RETINAL DEFECTS IN ALZHEIMERS DISEASE

我们最近的报告(Hinton，Sadun，Blanks和Miller，1986；参考 至附录第3项)记录了视网膜的参与 在神经退行性变化的星座中， 阿尔茨海默病(AD)。视网膜全视网膜病变的初步分析 与广泛的轴突变性一起出现在 AD患者的视神经，提示视网膜神经节 AD患者的细胞正在大量退化。视网膜 神经节细胞层的变化特别耐人寻味， 因为它们与神经原纤维缠绕或 神经炎斑块，表明这些特征不是必需的 在阿尔茨海默病中发现神经元丢失。该项目将重点放在 阿尔茨海默病患者视网膜组织病理学与正常对照组的比较 年龄匹配的“对照组”的视网膜。研究将包括：(1) 视网膜整体和放射状切片的形态计量学分析 以确定剩余的数量、大小和分布 神经节细胞，以及(2)胆碱能 视网膜中的神经递质系统。的后一个方面 项目是极其重要的，因为 乙酰胆碱(ACh)被怀疑在 阿尔茨海默病发病机制。视网膜也可能表现出异常 胆碱能神经递质系统，类似于 AD患者的海马区、额叶皮质和基底核。 (3)我们将确定是否存在选择性损害 视网膜中的神经肽，因为有报道称有一个亚类 生长抑素阳性神经元和神经肽Y神经元 都会在公元后受到影响。(4)最后，我们将确定血管是否 阿尔茨海默病患者视网膜存在病理改变。我们将衡量 电子显微镜下视网膜毛细血管基底膜厚度 在显微镜下观察和测定血管密度。 凝集素RCA(Ricinis Communications A)作为血管标记物。 这些对视网膜组织的研究结果将是相互关联的 随着疾病的严重程度和神经退行性变 阿尔茨海默病患者中枢神经系统的变化改进 对AD中发生的退行性变化的理解将 帮助定义一类特定的神经元，它们容易受到 病理过程，并应有助于阐明退行性变 这一毁灭性疾病背后的过程。

Our recent report (Hinton, Sadun, Blanks and Miller, 1986; refer to Appendix item No. 3) documented the involvement of the retina in the constellation of neurodegenerative changes present in Alzheimer's disease (AD). Preliminary analyses of retinal whole- mounts, together with the widespread axonal degeneration seen in the optic nerves of AD patients, suggest that the retinal ganglion cells of AD patients are degenerating in high numbers. The retinal changes in the ganglion cell layer are particularly intriguing, since they are not associated with neurofibrillary tangles or neuritic plaques, suggesting that these features are not requisite for the neuronal loss found in AD. This project will focus on the histopathology found in retinas of AD patients compared with retinas of age-matched "controls". Studies will include: (1) a morphometric analysis of retinal whole-mounts and radial sections to determine the number, size and distribution of the remaining ganglion cells, and (2) an evaluation of the cholinergic neurotransmitter system, in the retina. The latter aspect of the project is extremely important as abnormally low levels of acetylcholine (ACh) are suspected to play a major role in the pathogenesis of AD. The retina may also exhibit abnormalities in the cholinergic neurotransmitter system, similar to those found in the hippocampus, frontal cortex and nucleus basalis of AD patients. (3) We will determine if there is selective damage to the neuropeptides in the retina, since there are reports of a subclass of somatostatin-positive neurons and of neuropeptide Y neurons that are affected in AD. (4) Finally, we will determine if vascular pathology exists in the retinas of AD patients. We will measure basement membrane thickness in retinal capillaries at the electron microscopic level and determine the density of blood vessels using the lectin RCA (Ricinis communis A) as a vascular marker. The results of these studies on retinal tissues will be correlated with the severity of the disease and with the neurodegenerative changes in the central nervous system of the AD patients. Improved understanding of the degenerative changes that occur in AD will help define a particular class of neurons that is vulnerable to the pathologic process, and should help to elucidate the degenerative processes that underlie this devastating disease.