Feeney L
Invest Ophthalmol Vis Sci. 1978 Jul;17(7):583-600.
The life history of melanin and lipofuscin granules of human retinal pigment epithelium (RPE) was studied in 30 human eyes spanning nine decades of life. Autofluorescent granules in the cytoplasm of eye over 30 years of age were shown, ultrastructurally and through lipid solvent extraction, to be lipofuscin granules. Sparse small fluorescent granules in infant eyes were secondary lysosomes containing small droplets of lipid. Flourescent substances in RPE granules of eyes less than 50 years old were more readily extracted with lipid solvents than those in very old eyes (greater than 70). Lipfuscin granules were positive for acid phosphatase and aryl sulfatase activity. Fusions between primary lysosomes and lipofuscin granules were common in older eyes, suggesting that the over-all degradative process involves repeated injection of lysosomal enzymes, i.e., the initial fusion of lysosomes with phagosomes (phagocytized outer segment disks) is only one of several attempts to hydrolyze the membranous material. Some melanin granules showed hydrolytic enzyme reactions. By use of enzyme cytochemistry, fluorescence microscopy, and lipid extraction two types of melanin-containing complex granules were identified: melanin with a cortex of lipofuscin (melanolipofuscin) and melanin with a cortex of nonlipid, enzyme reactive material (melanolysosomes). These findings indicate that melanin commonly becomes incorporated into the lysosomal system of the RPE cell and suggests that it undergoes modification or degradation there. These studies indicate that a dynamic, complex interrelationship exists between the various components of the phagolysosomal system and the melanin granules in the RPE cytoplasm. Also, the observed variation from one human eye to another in the content and lipid extractability of RPE lipofuscin granules suggests that there may be differences in lipid composition of phagocytized photoreceptor disks and/or differences in the degradation of these lipids in the phagolysosomal system of the RPE cell.
对30只年龄跨度达九十年的人眼进行研究，以探讨人类视网膜色素上皮（RPE）中黑色素和脂褐素颗粒的生命历程。通过超微结构观察及脂质溶剂萃取发现，30岁以上人眼细胞质中的自发荧光颗粒为脂褐素颗粒。婴儿眼中稀疏的小荧光颗粒是含有小脂滴的次级溶酶体。小于50岁人眼的RPE颗粒中的荧光物质比大于70岁的极老龄人眼中的荧光物质更易被脂质溶剂萃取。脂褐素颗粒的酸性磷酸酶和芳基硫酸酯酶活性呈阳性。在老龄人眼中，初级溶酶体与脂褐素颗粒之间的融合很常见，这表明总体降解过程涉及溶酶体酶的反复注入，即溶酶体与吞噬体（吞噬的外节盘）的初始融合只是水解膜性物质的几次尝试之一。一些黑色素颗粒显示出水解酶反应。通过酶细胞化学、荧光显微镜检查和脂质萃取，鉴定出两种含黑色素的复合颗粒：具有脂褐素皮质的黑色素（黑素脂褐素）和具有非脂质、酶反应性物质皮质的黑色素（黑素溶酶体）。这些发现表明，黑色素通常会融入RPE细胞的溶酶体系统，并提示其在那里会发生修饰或降解。这些研究表明，吞噬溶酶体系统的各种成分与RPE细胞质中的黑色素颗粒之间存在动态、复杂的相互关系。此外，观察到的人眼之间RPE脂褐素颗粒含量和脂质可萃取性的差异表明，吞噬的光感受器盘的脂质组成可能存在差异，和/或这些脂质在RPE细胞的吞噬溶酶体系统中的降解存在差异。
