Katz Martin L, Wendt Kristy D, Sanders Douglas N
Department of Ophthalmology, University of Missouri School of Medicine, Mason Eye Institute, One Hospital Dr., Columbia, MO 65212, USA.
Mech Ageing Dev. 2005 Apr;126(4):513-21. doi: 10.1016/j.mad.2004.11.004. Epub 2004 Dec 24.
During senescence, autofluorescent lysosomal storage bodies known as lipofusin or age pigment accumulate in many post-mitotic types of cells. Among these cell types is the retinal pigment epithelium (RPE) of the mammalian eye. The mechanisms of lipofuscin formation and accumulation have been studied more extensively in the RPE than in any other cell type. Substantial evidence indicates that Vitamin A derivatives (retinoids) are required for RPE lipofuscin formation. The RPE and adjacent retina contain retinoids in the forms of retinol, retinyl esters, and retinaldehyde. Previous research has demonstrated that retinaldehydes are directly involved in the formation of one RPE lipofuscin fluorophore. However, RPE lipofuscin contains many other fluorophores. It has not been determined which retinoids are involved in the formation of these fluorescent compounds. Mice with a mutation in the Rpe65 gene contain substantial levels of retinol and retinyl esters in the RPE, but little if any retinaldehydes in either the RPE or retina. Therefore, these mice could be used to determine whether retinaldehydes are required for formation of all of the RPE lipofuscin fluorophores. Normal mice were given intraocular injections of a protease inhibitor, which resulted in the rapid accumulation in the RPE of lipofuscin-like inclusions. These inclusions exhibited fluorescence properties typical of RPE lipofuscin. Rpe65-/- mice treated with the protease inhibitor also accumulated inclusions similar to those observed in the normal mice. However, these inclusions did not fluoresce under the conditions used to visualize lipofuscin fluorescence. These findings indicate that the aldehyde form of Vitamin A is required for the formation of not only one, but all of the RPE lipofuscin fluorophores.
在衰老过程中，被称为脂褐素或老年色素的自发荧光溶酶体储存体在许多终末分化细胞类型中积累。这些细胞类型包括哺乳动物眼睛的视网膜色素上皮（RPE）。与其他任何细胞类型相比，在RPE中对脂褐素形成和积累机制的研究更为广泛。大量证据表明，维生素A衍生物（类视黄醇）是RPE脂褐素形成所必需的。RPE和相邻的视网膜含有视黄醇、视黄酯和视黄醛形式的类视黄醇。先前的研究表明，视黄醛直接参与一种RPE脂褐素荧光团的形成。然而，RPE脂褐素含有许多其他荧光团。尚未确定哪些类视黄醇参与这些荧光化合物的形成。Rpe65基因发生突变的小鼠在RPE中含有大量的视黄醇和视黄酯，但在RPE或视网膜中几乎没有视黄醛。因此，这些小鼠可用于确定视黄醛是否是所有RPE脂褐素荧光团形成所必需的。给正常小鼠眼内注射一种蛋白酶抑制剂，导致RPE中迅速积累脂褐素样包涵体。这些包涵体表现出RPE脂褐素典型的荧光特性。用蛋白酶抑制剂处理的Rpe65-/-小鼠也积累了与正常小鼠中观察到的类似的包涵体。然而，在用于观察脂褐素荧光的条件下，这些包涵体不发荧光。这些发现表明，维生素A的醛形式不仅是一种，而且是所有RPE脂褐素荧光团形成所必需的。
