Accelerated aging in glaucoma: immunohistochemical assessment of advanced glycation end products in the human retina and optic nerve head.
Accelerated aging in glaucoma: immunohistochemical assessment of advanced glycation end products in the human retina and optic nerve head.
复制标题
DOI：
10.1167/iovs.06-0737
复制
发表时间：
2007-03
影响因子：
4.4
通讯作者：
G. Tezel;C. Luo;Xiangjun Yang
中科院分区：
文献类型：
--
作者：
G. Tezel;C. Luo;Xiangjun Yang
目的研究晚期糖基化终产物(AGEs)与青光眼神经退行性变中氧化应激之间的协同作用，探讨AGEs与青光眼的关系。方法对38只青光眼供体和30只年龄匹配的非青光眼供体的视网膜和视神经头组织切片进行AGEs及其受体RAGE免疫标记的范围和细胞定位。结果年龄和RAGE免疫标记的范围在年龄较大的供眼大于年轻供眼。然而，与年龄匹配的对照组相比，在青光眼视网膜和视神经头中可以检测到AGEs的增加和RAGE的上调。虽然一些视网膜神经节细胞(RGCs)和胶质细胞显示AGEs的细胞内免疫标记，但青光眼中增加的AGE免疫标记主要是细胞外的，包括视神经头部的板层筛板。在视网膜节细胞上可检测到一些RAGE免疫标记；然而，青光眼患者RAGE免疫标记的增加主要见于神经胶质细胞，主要是Müller细胞。结论由于AGEs的产生是一个年龄相关的事件，青光眼组织中年龄积累的增加支持了青光眼伴随着神经变性的加速衰老过程。青光眼中年龄积累的潜在后果之一似乎是它导致筛板僵硬的增加。视网膜神经节细胞和神经胶质细胞上RAGE的存在也使它们容易受到AGE介导的事件的影响，这可能会在青光眼神经变性过程中促进细胞死亡或功能障碍。
PURPOSE This study aimed to determine the association between advanced glycation end products (AGEs) and glaucoma based on the known synergism between oxidative stress with AGEs and the evidence of oxidative stress during glaucomatous neurodegeneration. METHODS The extent and cellular localization of immunolabeling for AGEs and their receptor, RAGE, were determined in histologic sections of the retina and optic nerve head obtained from 38 donor eyes with glaucoma and 30 eyes from age-matched donors without glaucoma. RESULTS The extent of AGE and RAGE immunolabeling was greater in older than in younger donor eyes. However, compared with age-matched controls, an enhanced accumulation of AGEs and an up-regulation of RAGE were detectable in the glaucomatous retina and optic nerve head. Although some retinal ganglion cells (RGCs) and glia exhibited intracellular immunolabeling for AGEs, increased AGE immunolabeling in glaucomatous eyes was predominantly extracellular and included laminar cribriform plates in the optic nerve head. Some RAGE immunolabeling was detectable on RGCs; however, increased RAGE immunolabeling in glaucomatous eyes was predominant on glial cells, primarily Müller cells. CONCLUSIONS Given that the generation of AGEs is an age-dependent event, increased AGE accumulation in glaucomatous tissues supports that an accelerated aging process accompanies neurodegeneration in glaucomatous eyes. One of the potential consequences of AGE accumulation in glaucomatous eyes appears to be its contribution to increased rigidity of the lamina cribrosa. The presence of RAGE on RGCs and glia also makes them susceptible to AGE-mediated events through receptor-mediated signaling, which may promote cell death or dysfunction during glaucomatous neurodegeneration.