伴随年龄积聚在视网膜色素上皮（RPE）细胞中的脂褐质色素与年龄相关性黄斑变性（AMD）的发病机制密切相关。维生素A醛衍生物是视黄醛代谢紊乱的生物标志物，构成了脂褐质色素的主要组成部份，而且一旦形成，基因疗法和药物控制都无法逆转。脂褐质色素A2与研究最为广泛的A2E相比较，具有独特的分子结构、较弱的荧光性及更强的光敏感性。我们最近的预实验研究发现：A2色素在AMD动物模型ABCA4-/-RDH8-/-小鼠后眼罩中的含量显著上调，甚至明显超过了A2E的含量，具有很高的生理学意义。但是，A2色素与AMD致病机理的关联性尚不明确。细胞毒性预实验也揭示了A2色素积聚在RPE细胞或蓝光（430 nm）照射负载A2色素的RPE细胞都会引起细胞活力显著下降。因此本项目主要在我们前期工作的基础上，拟开展脂褐质色素A2在视网膜色素上皮变性发生发展中的作用机制及其靶向降解和转移清除的研究，具有重要的科学意义。

Lipofuscin pigments that accumulate in retinal pigment epithelial (RPE) cells with age are implicated in the pathogenesis of age-related macular degeneration (AMD). Vitamin A aldehyde-derived compounds serve as the biomarkers of retinal metabolism disorders, and constitute major components of lipofuscin pigments. Once these pigments are formed, neither gene therapy nor drug control can reverse the phenomenon. In comparison with A2E, the most studied lipofuscin pigment, A2 pigment exhibits a unique molecular structure, weaker fluorescence and greater photosensitivity. Our most recent preliminary experiments found out that the level of A2 was remarkably up-regulated and even significantly greater than A2E in posterior eyecups of ABCA4-/-RDH8-/- mice, an experimental animal model of AMD, indicating that A2 was of higher physiological significance. However, the relationship of A2 pigment to the pathological mechanisms of AMD remains unclear. Preliminary cytotoxicity tests also revealed that either the accumulation of A2 pigment in RPE cells or blue-light irradiation of RPE cells laden with A2 pigment significantly decreased cell viability. Therefore, based on our early work, this study will focus on the effect and mechanism of lipofuscin pigment A2 in onset and progression of retinal pigment epithelium degeneration as well as target elimination of A2 pigment by degradation and transfer, and has important scientific significance.