Glenn Josephine V, Stitt Alan W
Centre for Vision & Vascular Science, School of Medicine, Dentistry & Biomedical Sciences, Queen's University Belfast, Belfast, BT12 6BA, Northern Ireland, UK.
Biochim Biophys Acta. 2009 Oct;1790(10):1109-16. doi: 10.1016/j.bbagen.2009.04.016. Epub 2009 May 3.
The retina is exposed to a lifetime of potentially damaging environmental and physiological factors that make the component cells exquisitely sensitive to age-related processes. Retinal ageing is complex and a raft of abnormalities can accumulate in all layers of the retina. Some of this pathology serves as a sinister preamble to serious conditions such as age-related macular degeneration (AMD) which remains the leading cause of irreversible blindness in the Western world. The formation of advanced glycation end products (AGEs) is a natural function of ageing but accumulation of these adducts also represents a key pathophysiological event in a range of important human diseases. AGEs act as mediators of neurodegeneration, induce irreversible changes in the extracellular matrix, vascular dysfunction and pro-inflammatory signalling. Since many cells and tissues of the eye are profoundly influenced by such processes, it is fitting that advanced glycation is now receiving considerable attention as a possible pathogenic factor in visual disorders. This review presents the current evidence for a pathogenic role for AGEs and activation of the receptor for AGEs (RAGE) in initiation and progression of retinal disease. It draws upon the clinical and experimental literature and highlights the opportunities for further research that would definitively establish these adducts as important instigators of retinal disease. The therapeutic potential for novel agents that can ameliorate AGE formation of attenuate RAGE signalling in the retina is also discussed.
视网膜一生都暴露于潜在的有害环境和生理因素中，这些因素使得组成细胞对与年龄相关的过程极为敏感。视网膜老化是复杂的，一系列异常情况会在视网膜的所有层中累积。其中一些病理变化是诸如年龄相关性黄斑变性（AMD）等严重疾病的不祥先兆，而AMD仍然是西方世界不可逆失明的主要原因。晚期糖基化终末产物（AGEs）的形成是衰老的自然过程，但这些加合物的积累也是一系列重要人类疾病中的关键病理生理事件。AGEs作为神经退行性变的介质，可诱导细胞外基质发生不可逆变化、血管功能障碍和促炎信号传导。由于眼睛的许多细胞和组织都受到这些过程的深刻影响，因此晚期糖基化作为视觉障碍可能的致病因素，目前受到了相当多的关注，这是恰当的。本综述介绍了AGEs及其受体（RAGE）的激活在视网膜疾病的发生和发展中起致病作用的现有证据。它借鉴了临床和实验文献，并强调了进一步研究的机会，这些研究将明确确定这些加合物是视网膜疾病的重要诱因。还讨论了能够改善视网膜中AGE形成或减弱RAGE信号传导的新型药物的治疗潜力。
