Muraleva Natalia A, Tikhonov Dmitry I, Zhdankina Anna A, Plotnikov Mark B, Khlebnikov Andrei I, Logvinov Sergey V, Kolosova Nataliya G
Federal Research Center Institute of Cytology and Genetics SB RAS, 10 Pr. Akad. Lavrentieva, Novosibirsk 630090, Russia.
Department of Histology, Embryology and Cytology, Siberian State Medical University, Tomsk 634055, Russia.
Cells. 2025 Jun 13;14(12):896. doi: 10.3390/cells14120896.
Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. AMD development is associated with inflammation, oxidative stress, and a progressive proteostasis imbalance, in whose regulation, c-Jun N-terminal kinases (JNKs) play a crucial role. JNK inhibition is being discussed as a new way to prevent and treat AMD, but there are no data on JNK signaling in the retina and its changes with age and with AMD development. Here, for the first time, we assessed JNK-signaling activity in the retina and did not detect its age-related changes in healthy Wistar rats. By contrast, manifestation and progression of the AMD-like pathology in OXYS rats occurred simultaneously with JNK pathway activation. We also confirmed that selective JNK3 inhibitor 11H-indeno[1,2-b]quinoxalin-11-one oxime sodium salt (IQ-1S) can suppress neurodegenerative changes in the OXYS rat retina. Its effects were prevention of the destructive changes in retinal synapses and the suppression of the JNK signaling pathway activity during active progression of AMD signs in OXYS rats.
年龄相关性黄斑变性（AMD）是全球不可逆视力损害的主要原因。AMD的发展与炎症、氧化应激以及渐进性的蛋白质稳态失衡有关，在这些过程的调节中，c-Jun氨基末端激酶（JNKs）起着关键作用。JNK抑制作为预防和治疗AMD的新方法正在被讨论，但目前尚无关于视网膜中JNK信号及其随年龄和AMD发展变化的数据。在此，我们首次评估了视网膜中的JNK信号活性，并未在健康的Wistar大鼠中检测到其与年龄相关的变化。相比之下，OXYS大鼠中AMD样病理的表现和进展与JNK途径激活同时发生。我们还证实，选择性JNK3抑制剂11H-茚并[1,2-b]喹喔啉-11-酮肟钠盐（IQ-1S）可以抑制OXYS大鼠视网膜中的神经退行性变化。其作用是预防视网膜突触的破坏性变化，并在OXYS大鼠AMD体征的活跃进展过程中抑制JNK信号通路的活性。
Zotero 插件
