PDF(Pubmed)
Abstract：
Dysfunction of the retinal pigment epithelium (RPE) is associated with several diseases characterized by retinal degeneration, such as diabetic retinopathy (DR). However, it has recently been proposed that outer retinal neurons also participate in the damage triggering. Therefore, we have evaluated the possible crosstalk between RPE and photoreceptors in priming and maintaining oxidative damage of the RPE. For this purpose, we used ARPE-19 cells as a model of human RPE, grown in normal (NG, 5.6 mM) or high glucose (HG, 25 mM) and unoxidized (UOx) or oxidized (Ox) mammalian retinal rod outer segments (OSs). ARPE-19 cells were efficient at phagocytizing rod OSs in both NG and HG settings. However, in HG, ARPE-19 cells treated with Ox-rod OSs accumulated MDA and lipofuscins and displayed altered LC3, GRP78, and caspase 8 expression compared to untreated and UOx-rod-OS-treated cells. Data suggest that early oxidative damage may originate from the photoreceptors and subsequently extend to the RPE, providing a new perspective to the idea that retinal degeneration depends solely on a redox alteration of the RPE.
摘要：
视网膜色素上皮（RPE）的功能障碍与几种以视网膜变性为特征的疾病有关，如糖尿病视网膜病变（DR）。然而,最近有人提出，视网膜外神经元也参与了损伤触发。因此,我们已经评估了RPE和光感受器在引发和维持RPE的氧化损伤中可能的串扰。为此,我们使用ARPE-19细胞作为人RPE的模型，正常生长(NG，5.6mM）或高葡萄糖（HG，25mM）和未氧化（UOx）或氧化（Ox）的哺乳动物视网膜杆外段（OS）。在NG和HG设置中，ARPE-19细胞在吞噬杆OS方面都是有效的。然而,在HG，与未处理和UOx-rod-OS处理的细胞相比，用Ox-rod-OS处理的ARPE-19细胞积累了MDA和脂褐素，并显示出改变的LC3，GRP78和caspase8表达。数据表明，早期氧化损伤可能起源于光感受器，随后扩展到RPE，为视网膜变性仅取决于RPE的氧化还原改变提供了新的视角。
