Shandong Key Laboratory of Glycoscience and Glycotechnology, Key Laboratory of Marine Drugs of Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China.
Mar Drugs. 2023 Feb 22;21(3):137. doi: 10.3390/md21030137.
Age-related macular degeneration (AMD) is the leading cause of vision loss among the elderly. The progression of AMD is closely related to oxidative stress in the retinal pigment epithelium (RPE). Here, a series of chitosan oligosaccharides (COSs) and -acetylated derivatives (NACOSs) were prepared, and their protective effects on an acrolein-induced oxidative stress model of ARPE-19 were explored using the MTT assay. The results showed that COSs and NACOs alleviated APRE-19 cell damage induced by acrolein in a concentration-dependent manner. Among these, chitopentaose (COS-5) and its -acetylated derivative (N-5) showed the best protective activity. Pretreatment with COS-5 or N-5 could reduce intracellular and mitochondrial reactive oxygen species (ROS) production induced by acrolein, increase mitochondrial membrane potential, GSH level, and the enzymatic activity of SOD and GSH-Px. Further study indicated that N-5 increased the level of nuclear Nrf2 and the expression of downstream antioxidant enzymes. This study revealed that COSs and NACOSs reduced the degeneration and apoptosis of retinal pigment epithelial cells by enhancing antioxidant capacity, suggesting that they have the potential to be developed into novel protective agents for AMD treatment and prevention.
年龄相关性黄斑变性（AMD）是老年人视力丧失的主要原因。AMD 的进展与视网膜色素上皮（RPE）中的氧化应激密切相关。在这里，我们制备了一系列壳聚糖寡糖（COS）及其乙酰化衍生物（NACOS），并通过 MTT 测定法探讨了它们对丙烯醛诱导的 ARPE-19 氧化应激模型的保护作用。结果表明，COSs 和 NACOs 以浓度依赖的方式缓解了丙烯醛诱导的 APRE-19 细胞损伤。其中，壳五糖（COS-5）及其乙酰化衍生物（N-5）表现出最佳的保护活性。用 COS-5 或 N-5 预处理可以减少丙烯醛诱导的细胞内和线粒体活性氧（ROS）的产生，增加线粒体膜电位、GSH 水平以及 SOD 和 GSH-Px 的酶活性。进一步的研究表明，N-5 增加了核 Nrf2 的水平和下游抗氧化酶的表达。本研究表明，COSs 和 NACOSs 通过增强抗氧化能力来减少视网膜色素上皮细胞的变性和凋亡，这表明它们有可能被开发成治疗和预防 AMD 的新型保护剂。
