Jin Hong Lan, Lee Sung-Chan, Kwon Yong Sam, Choung Se-Young, Jeong Kwang Won
J Pharm Biomed Anal. 2016 Jan 5;117:560-7. doi: 10.1016/j.jpba.2015.10.010.
Age-related macular degeneration (AMD) is a common retinal disease that leads to irreversible central vision loss in the elderly population. Recent studies have identified many factors related to the development of dry AMD, such as aging, cigarette smoking, genetic predispositions, and oxidative stress, eventually inducing the accumulation of lipofuscin, which is one of the most critical risk factors. One of the major lipofuscins in retinal pigment epithelial (RPE) cells is N-retinylidene-N-retinylethanolamine (also known as A2E), a pyridinium bis-retinoid. Currently there is a lack of effective therapy to prevent or restore vision loss caused by dry AMD. Recent studies have shown that 430 nm blue light induces the oxidation of A2E and the activation of caspase-3 to subsequently cause the death of RPE cells, suggesting that removal of A2E from retinal pigment cells might be critical for preventing AMD. Here, we developed a fluorescence-labeled A2E analog (A2E-BDP) that functions similar to A2E in RPE cells, but is more sensitive to detection than A2E. A2E-BDP-based tracing of intracellular A2E will be helpful, not only for studying the accumulation and removal of A2E in human RPE cells but also for identifying possible inhibitors of AMD.
年龄相关性黄斑变性（AMD）是一种常见的视网膜疾病，可导致老年人群不可逆转的中心视力丧失。最近的研究已经确定了许多与干性AMD发展相关的因素，如衰老、吸烟、遗传易感性和氧化应激，最终导致脂褐素的积累，这是最关键的危险因素之一。视网膜色素上皮（RPE）细胞中的主要脂褐素之一是N-视黄叉基-N-视黄基乙醇胺（也称为A2E），一种吡啶鎓双视黄醛。目前缺乏有效的疗法来预防或恢复由干性AMD引起的视力丧失。最近的研究表明，430nm蓝光诱导A2E氧化和半胱天冬酶-3激活，随后导致RPE细胞死亡，这表明从视网膜色素细胞中去除A2E可能对预防AMD至关重要。在这里，我们开发了一种荧光标记的A2E类似物（A2E-BDP），它在RPE细胞中的功能与A2E相似，但比A2E更易于检测。基于A2E-BDP追踪细胞内A2E不仅有助于研究A2E在人RPE细胞中的积累和清除，还有助于鉴定可能的AMD抑制剂。
