CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration
CD44 aptamer mediated cargo delivery to lysosomes of retinal pigment epithelial cells to prevent age-related macular degeneration
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DOI：
10.1016/j.bbrep.2019.100642
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发表时间：
2019-07-01
影响因子：
2.7
通讯作者：
Neerathilingam, Muniasamy
中科院分区：
文献类型：
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作者：
Chandola, Chetan;Casteleijn, Marco G.;Neerathilingam, Muniasamy
年龄相关性黄斑变性（AMD）是一种进行性神经退行性疾病，会导致老年人中央视力严重丧失。视网膜色素上皮 (RPE) 细胞的健康对于 AMD 的发病至关重要。慢性氧化应激和溶酶体活性丧失是 AMD 期间 RPE 细胞死亡的主要原因。因此，开发一种用于在 RPE 细胞中靶向溶酶体递送治疗蛋白/药物的分子对于预防 AMD 期间 RPE 细胞死亡非常重要。以人RPE细胞系（ARPE-19细胞）为研究模型，我们证实过氧化氢（H2O2）诱导的氧化应激导致RPE细胞中CD44细胞表面受体过度表达；因此，它是氧化应激期间特异性递送至 RPE 细胞的重要靶点。我们还证明，已知的核酸 CD44 适体 - 与荧光探针 (FITC) 缀合 - 被递送到表达 CD44 的 ARPE-19 细胞的溶酶体中。因此，作为概念证明，我们证明 CD44 适体可用于在氧化应激下将货物通过溶酶体递送至 RPE 细胞，类似于 AMD 条件。由于氧化应激可能诱发湿性和干性 AMD，以及增殖性玻璃体视网膜病变，因此 CD44 适体可用作载体，用于在 RPE 细胞中显示氧化应激的眼部疾病中靶向溶酶体递送治疗药物。
Age related macular degeneration (AMD) is a progressive, neurodegenerative disorder that leads to the severe loss of central vision in elderlies. The health of retinal pigment epithelial (RPE) cells is critical for the onset of AMD. Chronic oxidative stress along with loss of lysosomal activity is a major cause for RPE cell death during AMD. Hence, development of a molecule for targeted lysosomal delivery of therapeutic protein/drugs in RPE cells is important to prevent RPE cell death during AMD. Using human RPE cell line (ARPE-19 cells) as a study model, we confirmed that hydrogen peroxide (H2O2) induced oxidative stress results in CD44 cell surface receptor overexpression in RPE cells; hence, an important target for specific delivery to RPE cells during oxidative stress. We also demonstrate that the known nucleic acid CD44 aptamer - conjugated with a fluorescent probe (FITC) - is delivered into the lysosomes of CD44 expressing ARPE-19 cells. Hence, as a proof of concept, we demonstrate that CD44 aptamer may be used for lysosomal delivery of cargo to RPE cells under oxidative stress, similar to AMD condition. Since oxidative stress may induce wet and dry AMD, both, along with proliferative vitreoretinopathy, CD44 aptamer may be applicable as a carrier for targeted lysosomal delivery of therapeutic cargoes in ocular diseases showing oxidative stress in RPE cells.