伴随年龄积聚在视网膜色素上皮（RPE）中的非降解性脂褐素是复杂的荧光混合物，并与干性年龄相关性黄斑变性（AMD）的发病机制密切相关。A2E作为最早被发现的RPE脂褐素的主要成份获得了最广泛的关注。Rdh8-/-Abca4-/-双敲小鼠展现了干性AMD的一些象征性表型。我们近期在Rdh8-/-Abca4-/-小鼠后眼罩及人、猪RPE中发现了一个未知的脂褐素成份（Lipof8）。高效液相色谱法定量分析显示：Lipof8在Rdh8-/-Abca4-/-小鼠后眼罩中的含量略高于A2E，具有很高的生理学意义。细胞毒性预实验研究揭露了Lipof8积聚在猪原代RPE细胞或蓝绿光（510 nm）照射负载Lipof8的猪原代RPE细胞均会引起细胞活力显著下降。因此本项目拟开展脂褐素新成份Lipof8的分子结构、特性、体内生物合成通路、仿生合成手段及其在RPE退化发生发展中的作用机制研究，具有重要的科学意义。

Nondegradable lipofuscin that accumulate in retinal pigment epithelial (RPE) cells with age is a complex fluorescent mixture, and implicated in the pathogenesis of dry age-related macular degeneration (AMD). A2E, a major fluorophore of RPE lipofuscin, is first identified, and has received the most extensive attention. Rdh8-/-Abca4-/- mice is a mouse model with defects in the visual (retinoid) cycle that displays some symbolic characteristics of dry AMD. We recently found out a previously unrecognized lipofuscin pigment called Lipof8 from posterior eyecups of Rdh8-/-Abca4-/- mice, and the RPE of pigs and humans. Quantitative analysis of Lipof8 by high-performed liquid chromatography manifested that the amount of Lipof8 was slightly higher than that of A2E in posterior eyecups of Rdh8-/-Abca4-/- mice, indicating that Lipof8 was of highly physiological significance. Preliminary cytotoxicity tests revealed that either the buildup of Lipof8 in primary porcine RPE (pRPE) cells or 510 nm blue-green light irradiation of primary pRPE cells laden with Lipof8 significantly decreased cell viability. Accordingly, this study will focus on molecular structure, characteristics, in vivo biosynthetic pathway, and biomimetic synthesis method of a new lipofuscin pigment (Lipof8) as well as the role of it in the degeneration of RPE, and has important scientific significance.