Zhu Danhong, Deng Xuemei, Xu Jing, Hinton David R
Arnold and Mabel Beckman Macular Research Center, Doheny Eye Institute, Los Angeles, CA 90033, USA.
Aging (Albany NY). 2009 Aug 12;1(8):740-5. doi: 10.18632/aging.100078.
Age-related macular degeneration (AMD), the leading cause of blindness in the elderly, targets the retinal pigment epithelium (RPE), a monolayer of cells at the back of the eye. As AMD progresses, it can develop into two distinct forms of late AMD: "dry," atrophic AMD, characterized by RPE senescence and geographic RPE loss, and "wet," neovascular AMD, characterized by RPE activation with abnormal growth of choroidal vessels. The genetic and molecular pathways that lead to these diverse phenotypes are currently under investigation. We have found that bone morphogenetic protein-4 (BMP4) is differentially expressed in atrophic and neovascular AMD. In atrophic AMD, BMP4 is highly expressed in RPE, and mediates oxidative stress induced RPE senescencein vitro via Smad and p38 pathways. In contrast, in neovascular AMD lesions, BMP4 expression in RPE is low, possibly a result of local expression of pro-inflammatory mediators. Thus, BMP4 may be involved in the molecular switch determining which phenotypic pathway is taken in the progression of AMD.
年龄相关性黄斑变性（AMD）是老年人失明的主要原因，其病变部位为视网膜色素上皮（RPE），即眼球后部的单层细胞。随着AMD的进展，它可发展为两种不同形式的晚期AMD：“干性”萎缩性AMD，其特征为RPE衰老和地图状RPE缺失；以及“湿性”新生血管性AMD，其特征为RPE激活并伴有脉络膜血管异常生长。导致这些不同表型的遗传和分子途径目前正在研究中。我们发现骨形态发生蛋白-4（BMP4）在萎缩性和新生血管性AMD中表达存在差异。在萎缩性AMD中，BMP4在RPE中高表达，并在体外通过Smad和p38途径介导氧化应激诱导的RPE衰老。相反，在新生血管性AMD病变中，RPE中BMP4表达较低，这可能是促炎介质局部表达的结果。因此，BMP4可能参与了决定AMD进展过程中采取何种表型途径的分子开关。
