Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells.
Vitamin A dimers trigger the protracted death of retinal pigment epithelium cells.
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DOI：
10.1038/cddis.2014.314
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发表时间：
2014-07-24
影响因子：
9
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中科院分区：
文献类型：
--
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导致失明的主要眼部神经退行性疾病（包括年龄相关性黄斑变性、Stargardt和Best疾病）的细胞事件尚不清楚。维生素A二聚体如N-亚视黄基-N-视黄乙醇胺（A2 E）在视网膜色素上皮（RPE）中的积累是视网膜变性之前最早可测量的事件之一。然而，这些二聚体在多大程度上导致组织变性尚不清楚。为了确定A2 E是否可以触发与退化的RPE和随后的细胞死亡相关的形态学变化，我们评估了其对培养的人RPE细胞（ARPE-19）的毒性。我们发现，A2 E引发了碎片的积累，随后是长期的死亡。A2 E的毒性是其前体视黄醇的14倍。测量结果显示，老年人眼中A2 E的浓度可能超过所有其他类维生素A的浓度，这可能是A2 E通过几种报告的机制触发细胞死亡的可能性。研究结果表明，维生素A二聚体（如A2 E）在人眼中的积累可能导致普遍存在的RPE碎片的形成，这是视网膜变性的早期迹象，预防或减少维生素A二聚体的积累是预防失明的谨慎策略。
Cellular events responsible for the initiation of major neurodegenerative disorders of the eye leading to blindness, including age-related macular degeneration, Stargardt and Best diseases, are poorly understood. Accumulation of vitamin A dimers, such as N-retinylidene-N-retinylethanolamine (A2E) in the retinal pigment epithelium (RPE), is one of the earliest measurable events preceding retinal degeneration. However, the extent to which these dimers contribute to tissue degeneration is not clear. To determine if A2E could trigger morphological changes associated with the degenerating RPE and subsequent cell death, we evaluated its toxicity to cultured human RPE cells (ARPE-19). We show that A2E triggered the accumulation of debris followed by a protracted death. A2E was up to≈14-fold more toxic than its precursor, retinaldehyde. Measurements reveal that the concentration of A2E in the aged human eye could exceed the concentration of all other retinoids, opening the possibility of A2E-triggered cell death by several reported mechanisms. Findings suggest that accumulation of vitamin A dimers such as A2E in the human eye might be responsible for the formation of ubiquitous RPE debris, an early indication of retinal degeneration, and that preventing or reducing the accumulation of vitamin A dimers is a prudent strategy to prevent blindness.
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