Boulton M, McKechnie N M, Breda J, Bayly M, Marshall J
Department of Clinical Ophthalmology, Institute of Ophthalmology, London, England.
Invest Ophthalmol Vis Sci. 1989 Jan;30(1):82-9.
Although the incomplete degradation of phagocytosed outer segment discs is thought to result in the formation of lipofuscin, there has to date been no proof of this concept. We report for the first time that cultured human retinal pigment epithelial (RPE) cells fed daily doses of isolated rod outer segments for periods of up to 3 months were capable of developing intracellular autofluorescent granules whose morphology and fluorescence characteristics were similar to lipofuscin. These autofluorescent granules were observed as early as 2 weeks following daily challenge with rod outer segments and the number of granules increased with the number of challenge doses until the experiment was terminated after 3 months of daily feeding. We also studied the effects of the antioxidant vitamin E and a drug, Centrophenoxine, which has been purported to slow the formation of lipofuscin formation in vivo. Neither of these additives given either with the challenge or subsequently had any effect on the formation of the intracellular granules. In conclusion, the development of these "lipofuscin-like" inclusions in cultured RPE may provide a model with which to study ageing processes and may provide an understanding of the increased lipofuscin accumulation observed in certain retinal pathologies.
尽管吞噬的视杆细胞外节盘不完全降解被认为会导致脂褐素的形成，但迄今为止尚无这一概念的证据。我们首次报告，每日给培养的人视网膜色素上皮（RPE）细胞投喂分离的视杆细胞外节，持续长达3个月，这些细胞能够形成细胞内自发荧光颗粒，其形态和荧光特征与脂褐素相似。早在每日用视杆细胞外节刺激2周后就观察到了这些自发荧光颗粒，并且颗粒数量随着刺激剂量的增加而增加，直到每日投喂3个月后实验结束。我们还研究了抗氧化剂维生素E和一种药物——盐酸甲氯芬酯的作用，据称该药物能减缓体内脂褐素的形成。在刺激时或之后给予这两种添加剂，均对细胞内颗粒的形成没有任何影响。总之，培养的RPE中这些“脂褐素样”内含物的形成可能为研究衰老过程提供一个模型，并可能有助于理解在某些视网膜病变中观察到的脂褐素积累增加的现象。
