Wang Michelle Y, Ross-Cisneros Fred N, Aggarwal Divya, Liang Chiao-Ying, Sadun Alfredo A
Department of Ophthalmology, Doheny Eye Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Acta Neuropathol. 2009 Sep;118(3):381-9. doi: 10.1007/s00401-009-0513-4. Epub 2009 Mar 11.
Although Alzheimer's disease (AD) has been shown to be associated with a true primary optic neuropathy, the underlying pathophysiology of this disease and in particular the optic nerve disorder is still poorly understood. The receptor for advanced glycation end products (RAGE) has been implicated in the pathogenesis of AD by mediating the transport of plasma amyloid-beta into the brain. Once ligated, RAGE can play a role in signal transduction, leading to amplification and perpetuation of inflammatory processes. As a key player in the reaction to CNS injury, astrocytes have been shown to associate with RAGE in a number of diseases, including AD. To investigate the role of RAGE and astrocytes in the pathogenesis of AD optic neuropathy, we conducted immunohistochemical studies to examine the presence of RAGE in donor eyes from patients with AD (n = 10) and controls (n = 3). Both qualitative observation and quantitative analyses using imaging software were used to document the extent of RAGE in the neural tissues. The intensity and extent of RAGE expression was more prominent in AD nerves compared to controls (P < 0.05). The RAGE immunoreactivity was observed in the microvasculature and in close proximity to astrocytic processes. While RAGE immunoreactivity increased with age, the increase was more precipitous in the AD group compared to the controls. The up-regulation of RAGE in the AD optic nerves indicates that RAGE may play a role in the pathophysiology of AD optic neuropathy.
尽管阿尔茨海默病（AD）已被证明与真正的原发性视神经病变有关，但这种疾病的潜在病理生理学，尤其是视神经疾病，仍知之甚少。晚期糖基化终产物受体（RAGE）通过介导血浆β淀粉样蛋白进入大脑，参与了AD的发病机制。一旦被连接，RAGE可在信号转导中发挥作用，导致炎症过程的放大和持续。作为中枢神经系统损伤反应的关键参与者，星形胶质细胞在包括AD在内的多种疾病中已被证明与RAGE有关。为了研究RAGE和星形胶质细胞在AD视神经病变发病机制中的作用，我们进行了免疫组织化学研究，以检查AD患者（n = 10）和对照组（n = 3）供体眼中RAGE的存在情况。使用成像软件进行定性观察和定量分析，以记录神经组织中RAGE的程度。与对照组相比，AD神经中RAGE表达的强度和程度更显著（P < 0.05）。在微血管和靠近星形胶质细胞突起处观察到RAGE免疫反应性。虽然RAGE免疫反应性随年龄增加，但与对照组相比，AD组的增加更为明显。AD视神经中RAGE的上调表明RAGE可能在AD视神经病变的病理生理学中起作用。
