Finnemann Silvia C, Leung Lawrence W, Rodriguez-Boulan Enrique
Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3842-7. doi: 10.1073/pnas.052025899.
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.
视网膜色素上皮（RPE）每日对消耗的光感受器外段进行吞噬作用，是维持视力的一项关键功能。衰老的RPE会积累脂褐素，其中主要的自发荧光成分包括N - 视黄叉基 - N - 视黄基乙醇胺（A2E）。我们研究了RPE培养物中生理水平的A2E对其吞噬外段能力的影响。A2E在培养的RPE细胞以及人RPE原位中均定位于溶酶体。培养中加载A2E的RPE细胞结合并内化的外段数量与对照RPE相同，这表明A2E不会改变吞噬作用的早期步骤。加载A2E的RPE能有效降解外段蛋白，但令人惊讶的是，在24小时内未能完全消化磷脂。由于眼部RPE吞噬作用的昼夜节律，脂质降解延迟可能会导致RPE中未消化物质的积累，这可能会促进年龄相关性黄斑变性的发展。
