A novel melano-lysosome in the retinal epithelium of rhesus monkeys
A novel melano-lysosome in the retinal epithelium of rhesus monkeys
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DOI：
10.1016/j.exer.2011.10.011
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发表时间：
2011-12-01
影响因子：
3.4
通讯作者：
Neuringer, Martha
中科院分区：
文献类型：
--
作者：
Gouras, Peter;Brown, Kristy;Neuringer, Martha
视网膜色素上皮（RPE）面临的大量吞噬细胞负荷被认为可能在困扰人类和猴子的年龄相关性黄斑变性（AMD）的发病机制中发挥作用。我们对RPE如何通过溶酶体作用降解吞噬体和其他细胞内物质的知识仍然是初步的。为了更好地了解溶酶体自噬和异噬在视网膜色素上皮中的作用及其在AMD发病中的可能作用，本文采用电镜技术观察和描述了年轻和老年恒河猴黄斑部视网膜色素上皮中的黑素体和溶酶体样细胞器的特征（Macaca mulatto），年龄为1岁、6岁、24岁、24岁、26岁和35岁。测量包括位于RPE细胞基底、中间和顶端区域的这些细胞器的数量、形状和大小。黑素体颜色均匀，呈圆形或椭圆形，数量随年龄增长而减少。较小的黑素体在RPE的基底侧更常见。在这些小的黑素体中，我们发现了一个细胞器，它在不同程度上失去了黑色素;在某些情况下几乎没有黑色素。由于黑色素损失，我们认为这种细胞器是一种独特类型的自噬黑素溶酶体，我们称之为1型溶酶体。我们发现了另一种细胞器，更典型的是溶酶体，我们称之为2型溶酶体。这种细胞器由含有处于不同降解阶段的黑素体的光基质组成。不含黑素体的2型溶酶体很少。随着年龄的增长，2型溶酶体的数量增加，而1型溶酶体的数量减少。吞噬体在年轻和年老的猴子中都很少见。它们与2型溶酶体密切接触，我们认为这是它们降解的原因。这种损失大部分由两种类型的溶酶体进行。其中一种，以前没有被定义为独特的，似乎在消化自己的黑色素时具有自噬作用;它被称为1型溶酶体。另一种是更典型的溶酶体，既有异噬性的吞噬体，又有自噬性的消化局部黑素体;它被称为2型溶酶体。随着年龄的增长，1型溶酶体减少，而2型溶酶体增加。黑色素的损失被认为是对RPE有害的，因为它降低了黑色素对抗光毒性和氧化应激的保护作用。吞噬体似乎通过与2型溶酶体的膜接触而降解。猴子中黑色素的损失和2型溶酶体的积累发生在比人类更早的年龄，这意味着更容易衰老加速了猴子中AMD的速率。(C)2011爱思唯尔有限公司保留所有权利。
The large phagocytic load that confronts the retinal pigment epithelium (RPE) is thought to play a possible role in the pathogenesis of age related macular degeneration (AMD) that afflicts both humans and monkeys. Our knowledge of how RPE degrades phagosomes and other intra-cellular material by lysosomal action is still rudimentary. In this paper we examine organelles that play a role in this process, melanosome, lysosomes and phagosomes, in the RPE of young and old rhesus monkeys in order to better understand lysosomal autophagy and heterophagy in the RPE and its possible role in AMD.We used electron microscopy to detect and describe the characteristics of melanosomes and lysosome-like organelles in the macular RPE of rhesus monkeys (Macaca mulatto) that were 1, 6, 24, 24, 26 and 35 years of age. The measurements include the number, shape and size of these organelles located in the basal, middle and apical regions of RPE cells. Phaagosomes were also examined but not counted or measured for size or shape because of their rarity.Melanosomes were homogeneously dark with a circular or elliptical shape and decreased in number with age. Smaller melanosomes were more common at the basal side of the RPE. Among the small melanosomes, we found an organelle that was losing melanin in varying degrees; in some cases was nearly devoid of melanin. Because of the melanin loss, we considered this organelle to be a unique type of autophagic melano-lysosome, which we called a Type 1 lysosome. We found another organelle, more canonically lysosomal, which we called a Type 2 lysosome. This organelle was composed of a light matrix containing melanosomes in various stages of degradation. Type 2 lysosomes without melanosomes were rare. Type 2 lysosomes increased while Type 1 decreased in number with age. Phagosomes were rare in both young and old monkeys. They made close contact with Type 2 lysosomes which we considered responsible for their degradation.Melanosomes are being lost from monkey RPE with age. Much of this loss is carried out by two types of lysosomes. One, not defined as unique before, appears to be autophagic in digesting its own melanin; it has been called a Type 1 lysosome. The other, a more canonical lysosome, is both heterophagic in digesting phagosomes and autophagic in digesting local melanosomes; it has been called a Type 2 lysosome. Type 1 lysosomes decrease while type 2 lysosomes increase with age. The loss of melanin is considered to be detrimental to the RPE since it reduces melanin's protective action against light toxicity and oxidative stress. Phagosomes appear to be degraded by membrane contacts with Type 2 lysosomes. The loss of melanin and the buildup of Type 2 lysosomes occur at an earlier age in monkeys than humans implying that a greater vulnerability to senescence accelerates the rate of AMD in monkeys. (C) 2011 Elsevier Ltd. All rights reserved.