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首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium
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The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium

机译：脂褐素成分A2E选择性抑制视网膜色素上皮细胞吞噬溶酶体降解感光磷脂

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摘要

Daily phagocytosis of spent photoreceptor outer segments is a critical maintenance function performed by the retinal pigment epithelium (RPE) to preserve vision. Aging RPE accumulates lipofuscin, which includes N-retinylidene-N-retinylethanolamine (A2E) as the major autofluorescent component. We studied the effect of physiological levels of A2E in RPE cultures on their ability to phagocytose outer segments. A2E localized to lysosomes in cultured RPE as well as in human RPE in situ. A2E-loaded RPE cells in culture bound and internalized identical numbers of outer segments as control RPE indicating that A2E does not alter early steps of phagocytosis. A2E-loaded RPE degraded outer segment proteins efficiently but, strikingly, failed to completely digest phospholipids within 24 h. Because of the circadian rhythm of RPE phagocytosis in the eye, a delay in lipid degradation would likely result in a build up of undigested material in RPE that could contribute to the development of age-related macular degeneration.
机译：废光感受器外部节段的每日吞噬作用是视网膜色素上皮（RPE）所执行的关键维护功能，以保持视力。老化的RPE会积聚脂褐素，其中包括N-视黄叉基-N-视黄基乙醇胺（A2E）作为主要的自发荧光成分。我们研究了RPE培养物中生理水平的A2E对吞噬外部区段的能力的影响。 A2E定位于原位培养的RPE和人RPE中的溶酶体。培养物中装载A2E的RPE细胞与对照RPE结合并内部化了相同数量的外部片段，表明A2E不会改变吞噬作用的早期步骤。载有A2E的RPE有效降解了外部片段蛋白，但引人注目的是，未能在24小时内完全消化磷脂。由于眼睛中RPE吞噬作用的昼夜节律，脂质降解的延迟可能会导致RPE中未消化物质的积累，这可能会导致与年龄相关的黄斑变性。

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