MECHANISMS 0F RETINAL DEFECTS IN ALZHEIMERS DISEASE

我们最近的报告（欣顿，萨顿，布兰克斯和米勒，1986年;参考 附录第3项）记录了视网膜受累 在神经退行性变化的星座中， 阿尔茨海默病（AD）。 视网膜整体的初步分析- 安装，连同广泛的轴突变性中看到， AD患者的视神经，提示视网膜神经节 AD患者的细胞大量退化。 视网膜 神经节细胞层的变化特别有趣， 因为它们与神经系统缠结无关， 神经炎斑块，表明这些特征不是必需的 在AD中发现的神经元缺失。 该项目将侧重于 AD患者视网膜中发现的组织病理学与 年龄匹配的“对照组”的视网膜。 研究将包括：（1）a 视网膜整体切片和放射状切片的形态计量学分析 以确定剩余的数量、大小和分布情况， 神经节细胞，和（2）胆碱能的评价 神经递质系统，在视网膜中。 后一个方面的 项目是非常重要的，因为异常低的水平， 乙酰胆碱（ACh）被怀疑在 AD的发病机制 视网膜也可能表现出异常， 胆碱能神经递质系统，类似于那些发现在 AD患者的海马、额叶皮质和基底核。 (3)我们将确定是否有选择性损害 视网膜中的神经肽，因为有报道称， 生长抑素阳性神经元和神经肽Y神经元， 受AD影响。 (4)最后，我们将确定血管 AD患者的视网膜中存在病理学。 我们将测量 电子显微镜下视网膜毛细血管基膜厚度 显微镜水平，并确定血管密度使用 凝集素RCA（Ricinis communis A）作为血管标记物。 这些对视网膜组织的研究结果将与 与疾病的严重程度和神经退行性疾病 AD患者中枢神经系统的变化。 改进 了解AD中发生的退行性变化将 帮助定义一个特定的神经元类别， 病理过程，并应有助于阐明退行性 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.