Age‐related macular degeneration (AMD), a leading cause of blindness, is characterized by mitochondrial dysfunction of retinal pigment epithelium (RPE) cells. EUK‐134 is a mimetic of SOD2 and catalase, widely used for its antioxidant properties in models of light‐induced damage or oxidative stress. However, its effects on the retina are not yet clear. Here, we investigated the capability of EUK‐134 in averting AMD using sodium iodate (NaIO3)‐induced Balb/c mouse and ARPE‐19 cells (adult RPE cell line). In vivo, EUK‐134 effectively antagonized NaIO3‐induced retinal deformation and prevented outer and inner nuclear layer thinning. In addition, it was found that the EUK‐134‐treated group significantly down‐regulated the expression of cleaved caspase‐3 compared with the group treated with NaIO3 alone. Our results found that EUK‐134 notably improved cell viability by preventing mitochondrial ROS accumulation‐induced membrane potential depolarization‐mediated apoptosis in NaIO3‐inducted ARPE‐19 cells. Furthermore, we found that EUK‐134 could inhibit p‐ERK, p‐p38, p‐JNK, p‐p53, Bax, cleaved caspase‐9, cleaved caspase‐3, and cleaved PARP by increasing Bcl‐2 protein expression. Additionally, we employed MAPK pathway inhibitors by SB203580 (a p38 inhibitor), U0126 (an ERK inhibitor), and SP600125 (a JNK inhibitor) to corroborate the aforementioned observation. The results support that EUK‐134 may effectively prevent mitochondrial oxidative stress‐mediated retinal apoptosis in NaIO3‐induced retinopathy.

中文翻译：

---

EUK-134在视网膜变性中的新应用：通过抑制MAPK/p53信号通路预防线粒体氧化应激引发的视网膜色素上皮细胞凋亡


年龄相关性黄斑变性（AMD）是导致失明的主要原因，其特征是视网膜色素上皮（RPE）细胞的线粒体功能障碍。 EUK-134 是 SOD2 和过氧化氢酶的模拟物，因其抗氧化特性而广泛用于光诱导损伤或氧化应激模型中。然而，其对视网膜的影响尚不清楚。在这里，我们使用碘酸钠 (NaIO3) 诱导的 Balb/c 小鼠和 ARPE-19 细胞（成人 RPE 细胞系）研究了 EUK-134 预防 AMD 的能力。在体内，EUK-134 有效拮抗 NaIO3 引起的视网膜变形，并防止外核层和内核层变薄。此外，发现与单独使用NaIO3处理组相比，EUK-134处理组显着下调了cleaved caspase-3的表达。我们的结果发现，EUK-134 通过防止 NaIO3 诱导的 ARPE-19 细胞中线粒体 ROS 积累诱导的膜电位去极化介导的细胞凋亡，显着提高细胞活力。此外，我们发现 EUK-134 可以通过增加 Bcl-2 蛋白表达来抑制 p-ERK、p-p38、p-JNK、p-p53、Bax、cleaved caspase-9、cleaved caspase-3 和 cleaved PARP。此外，我们还使用了 SB203580（一种 p38 抑制剂）、U0126（一种 ERK 抑制剂）和 SP600125（一种 JNK 抑制剂）等 MAPK 通路抑制剂来证实上述观察结果。结果支持 EUK-134 可以有效预防 NaIO3 诱导的视网膜病变中线粒体氧化应激介导的视网膜细胞凋亡。