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Photo-oxidative stress in the eye: role of retinal pigment epithelial pigments

机译:眼睛中的光氧化应激:视网膜色素上皮色素的作用

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Abstract: The pigments of the retinal pigment epithelium, i.e. the intracellular granules of melanin, lipofuscin, and melanolipofuscin, have been shown to catalyze free radical activity, especially when illuminated with visible or ultraviolet light. An important question is whether these reactions are sufficient to produce oxidative damage in the eye. To address this question, the relative photoreactivity of isolated RPE pigment granules towards polyunsaturated fatty acids has been determined, including the dark as well as the light-stimulated reactions. Hydroperoxide derivatives of docosahexaenoic acid were produced by irradiation with short wavelength ($LS 550 nm) visible light when RPE pigments were present. Although melanosomes exhibited the greatest light-induced activity in these reactions, lipofuscin granules induced peroxidation of fatty acids in the dark. In intact, cultured RPE cells, the existence of pigment-medicated photo-reactions were demonstrated with a fluorescent indicator probe of oxidation, 2',7'- dichlorofluorescein, that was photooxidized in probe-labeled cells in a wavelength dependence fashion with peak activity in the 450 to 500 nm region. This behavior resembled the action spectrum for melanin reactivity. These findings support the hypotheses that the RPE pigments contribute to general photooxidative stress in ocular tissue, and that accumulation of lipofuscin pigment contributes to age- related oxidative stress in the RPE.!23
机译:摘要:视网膜色素上皮的色素,即黑色素,脂褐素和黑素脂褐素的细胞内颗粒已被证明可催化自由基活性,尤其是在可见光或紫外线照射下。一个重要的问题是这些反应是否足以在眼睛中产生氧化损伤。为了解决这个问题,已经确定了分离的RPE颜料颗粒对多不饱和脂肪酸的相对光反应性,包括黑暗反应和光刺激反应。当存在RPE颜料时,通过短波长($ LS 550 nm)可见光照射产生二十二碳六烯酸的氢过氧化物衍生物。尽管黑素体在这些反应中表现出最大的光诱导活性,但脂褐素颗粒在黑暗中诱导脂肪酸的过氧化。在完整的培养RPE细胞中,用2',7'-二氯荧光素氧化的荧光指示剂探针证实了存在色素药物作用的光反应,该探针以波长依赖性的方式在探针标记的细胞中被光氧化,并具有峰值活性。在450至500 nm范围内。这种行为类似于黑色素反应的作用谱。这些发现支持以下假设:RPE色素有助于眼组织中的一般光氧化应激,而脂褐素色素的积累有助于RPE中与年龄相关的氧化应激。23

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