Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging
Dry Age-Related Macular Degeneration: Mechanisms, Therapeutic Targets, and Imaging
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DOI：
10.1167/iovs.13-12757
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发表时间：
2013-12-01
影响因子：
4.4
通讯作者：
Klingeborn, Mikael
中科院分区：
文献类型：
--
作者：
Rickman, Catherine Bowes;Farsiu, Sina;Klingeborn, Mikael
黄斑变性是西方社会中65岁以上人群中不可逆的视觉功能障碍的主要原因。患有AMD的患者被分类为患有早期疾病（早期AMD），其中视觉功能受到影响，或晚期AMD（通常表征为“湿性”新生血管性AMD、“干性”萎缩性AMD或两者），其中中心视力严重受损或丧失。直到最近，还没有治疗这种疾病的疗法。目前，最常见的湿性晚期AMD，脉络膜新生血管，一般响应于抗血管内皮生长因子疗法的治疗。然而，目前还没有治疗方法来恢复患有晚期萎缩性AMD的眼睛中丧失的视力。口服补充AMD相关眼病研究（AREDS）或AREDS 2制剂（抗氧化剂维生素C和E、叶黄素、玉米黄质和锌）已被证明可降低进展为晚期AMD的风险，尽管影响是在新生血管性而不是萎缩性AMD中。然而，最近的研究结果表明，早期AMD的几个特征可能是药物治疗的目标。研究已经确定，AMD的大部分遗传风险与补体基因有关。因此，正在寻求几种基于补体的治疗方法。针对AMD存款形成和蛋白质和/或脂质沉积的潜在治疗策略将进行讨论，包括抗淀粉样蛋白治疗。此外，还将探讨自噬在AMD中的作用以及通过调节抗氧化系统来预防氧化应激。最后，这些新疗法在临床试验及以后的成功依赖于早期检测、疾病分型和预测疾病进展，这些领域目前正在通过改进成像模式和功能测定而迅速转变。
Age-related macular degeneration is the leading cause of irreversible visual dysfunction in individuals over 65 in Western Society. Patients with AMD are classified as having early stage disease (early AMD), in which visual function is affected, or late AMD (generally characterized as either "wet" neovascular AMD, "dry" atrophic AMD or both), in which central vision is severely compromised or lost. Until recently, there have been no therapies available to treat the disorder(s). Now, the most common wet form of late-stage AMD, choroidal neovascularization, generally responds to treatment with anti-vascular endothelial growth factor therapies. Nevertheless, there are no current therapies to restore lost vision in eyes with advanced atrophic AMD. Oral supplementation with the Age-Related Eye Disease Study (AREDS) or AREDS2 formulation (antioxidant vitamins C and E, lutein, zeaxanthin, and zinc) has been shown to reduce the risk of progression to advanced AMD, although the impact was in neovascular rather than atrophic AMD. Recent findings, however, have demonstrated several features of early AMD that are likely to be druggable targets for treatment. Studies have established that much of the genetic risk for AMD is associated with complement genes. Consequently, several complement-based therapeutic treatment approaches are being pursued. Potential treatment strategies against AMD deposit formation and protein and/or lipid deposition will be discussed, including anti-amyloid therapies. In addition, the role of autophagy in AMD and prevention of oxidative stress through modulation of the antioxidant system will be explored. Finally, the success of these new therapies in clinical trials and beyond relies on early detection, disease typing, and predicting disease progression, areas that are currently being rapidly transformed by improving imaging modalities and functional assays.