PDF(Pubmed)
Abstract：
Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. Early to intermediate AMD is characterized by the accumulation of lipid- and protein-rich drusen. Late stages of the disease are characterized by the development of choroidal neovascularization, termed \"exudative\" or \"neovascular AMD,\" or retinal pigment epithelium (RPE) cell and photoreceptor death, termed \"geographic atrophy\" (GA) in advanced nonexudative AMD. Although we have effective treatments for exudative AMD in the form of anti-VEGF agents, they have no role for patients with GA. Neuroprotection strategies have emerged as a possible way to slow photoreceptor degeneration and vision loss in patients with GA. These approaches include reduction of oxidative stress, modulation of the visual cycle, reduction of toxic molecules, inhibition of pathologic protein activity, prevention of cellular apoptosis or programmed necrosis (necroptosis), inhibition of inflammation, direct activation of neurotrophic factors, delivery of umbilical tissue-derived cells, and RPE replacement. Despite active investigation in this area and significant promise based on preclinical studies, many clinical studies have not yielded successful results. We discuss selected past and current neuroprotection trials for AMD, highlight the lessons learned from these past studies, and discuss our perspective regarding remaining questions that must be answered before neuroprotection can be successfully applied in the field of AMD research.
摘要：
年龄相关性黄斑变性(AMD)是全球失明的主要原因。早期至中期AMD的特征在于富含脂质和蛋白质的玻璃疣的积累。该疾病的晚期以脉络膜新生血管的发展为特征，称为“渗出性”或“新生血管性AMD，“或视网膜色素上皮（RPE）细胞和光感受器死亡，在晚期非渗出性AMD中称为“地理萎缩”(GA)。尽管我们已经以抗VEGF药物的形式有效治疗渗出性AMD，它们对GA患者没有作用。神经保护策略已成为减缓GA患者的光感受器变性和视力丧失的可能方法。这些方法包括减少氧化应激，视觉周期的调制，减少有毒分子，抑制病理蛋白活性，预防细胞凋亡或程序性坏死（坏死），抑制炎症，直接激活神经营养因子，传递脐带组织来源的细胞，和RPE替换。尽管在这一领域进行了积极的调查，并且基于临床前研究，许多临床研究没有取得成功的结果。我们讨论了AMD过去和现在的神经保护试验，强调从这些过去的研究中吸取的教训，并讨论我们对神经保护在AMD研究领域成功应用之前必须回答的剩余问题的看法。
