Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1S
Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. The development of AMD is associated with inflammation, oxidative stress, and progressive proteostasis imbalance, in the regulation of which c-Jun N-terminal kinases (JNK) play a crucial role. JN...
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MDPI AG
2023-01-01
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| author | Anna A. Zhdankina Dmitry I. Tikhonov Sergey V. Logvinov Mark B. Plotnikov Andrei I. Khlebnikov Nataliya G. Kolosova |
| author_facet | Anna A. Zhdankina Dmitry I. Tikhonov Sergey V. Logvinov Mark B. Plotnikov Andrei I. Khlebnikov Nataliya G. Kolosova |
| author_sort | Anna A. Zhdankina |
| collection | DOAJ |
| description | Age-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. The development of AMD is associated with inflammation, oxidative stress, and progressive proteostasis imbalance, in the regulation of which c-Jun N-terminal kinases (JNK) play a crucial role. JNK inhibition is discussed as an alternative way for prevention and treatment of AMD and other neurodegenerative diseases. Here we assess the retinoprotective potential of the recently synthesized JNK inhibitor 11<i>H</i>-indeno[1,2-<i>b</i>]quinoxalin-11-one oxime sodium salt (IQ-1S) using senescence-accelerated OXYS rats as a model of AMD. The treatment with IQ-1S (50 mg/kg body weight intragastric) during the period of active disease development (from 4.5 to 6 months of age) improved some (but not all) histological abnormalities associated with retinopathy. IQ-1S improved blood circulation, increased the functional activity of the retinal pigment epithelium, reduced the VEGF expression in the endothelial cells, and increased the expression of PEDF in the neuroretina. The result was a decrease in the degeneration of photoreceptors and neurons of the inner layers. IQ-1S significantly improved the retinal ultrastructure and increased the number of mitochondria, which were significantly reduced in the neuroretina of OXYS rats compared to Wistar rats. It seems probable that using IQ-1S can be a good prophylactic strategy to treat AMD. |
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| language | English |
| last_indexed | 2024-03-11T09:07:17Z |
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| series | Biomedicines |
| spelling | doaj.art-be88d23bf9134be1b2cc7199018db19e2023-11-16T19:17:36ZengMDPI AGBiomedicines2227-90592023-01-0111239510.3390/biomedicines11020395Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1SAnna A. Zhdankina0Dmitry I. Tikhonov1Sergey V. Logvinov2Mark B. Plotnikov3Andrei I. Khlebnikov4Nataliya G. Kolosova5Department of Histology, Embryology and Cytology, Siberian State Medical University, 634055 Tomsk, RussiaDepartment of Histology, Embryology and Cytology, Siberian State Medical University, 634055 Tomsk, RussiaDepartment of Histology, Embryology and Cytology, Siberian State Medical University, 634055 Tomsk, RussiaDepartment of Pharmacology, Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk NRMC, 3 Lenin Ave., 634028 Tomsk, RussiaKizhner Research Center, Tomsk Polytechnic University, 30 Lenin Ave., 634050 Tomsk, RussiaFederal Research Center Institute of Cytology and Genetics SB RAS, Pr. Lavrentiev, 10, 630090 Novosibirsk, RussiaAge-related macular degeneration (AMD) is the leading cause of irreversible visual impairment worldwide. The development of AMD is associated with inflammation, oxidative stress, and progressive proteostasis imbalance, in the regulation of which c-Jun N-terminal kinases (JNK) play a crucial role. JNK inhibition is discussed as an alternative way for prevention and treatment of AMD and other neurodegenerative diseases. Here we assess the retinoprotective potential of the recently synthesized JNK inhibitor 11<i>H</i>-indeno[1,2-<i>b</i>]quinoxalin-11-one oxime sodium salt (IQ-1S) using senescence-accelerated OXYS rats as a model of AMD. The treatment with IQ-1S (50 mg/kg body weight intragastric) during the period of active disease development (from 4.5 to 6 months of age) improved some (but not all) histological abnormalities associated with retinopathy. IQ-1S improved blood circulation, increased the functional activity of the retinal pigment epithelium, reduced the VEGF expression in the endothelial cells, and increased the expression of PEDF in the neuroretina. The result was a decrease in the degeneration of photoreceptors and neurons of the inner layers. IQ-1S significantly improved the retinal ultrastructure and increased the number of mitochondria, which were significantly reduced in the neuroretina of OXYS rats compared to Wistar rats. It seems probable that using IQ-1S can be a good prophylactic strategy to treat AMD.https://www.mdpi.com/2227-9059/11/2/395age-related macular degenerationc-Jun N-Terminal Kinase Inhibitor IQ-1SOXYS rats |
| spellingShingle | Anna A. Zhdankina Dmitry I. Tikhonov Sergey V. Logvinov Mark B. Plotnikov Andrei I. Khlebnikov Nataliya G. Kolosova Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1S Biomedicines age-related macular degeneration c-Jun N-Terminal Kinase Inhibitor IQ-1S OXYS rats |
| title | Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1S |
| title_full | Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1S |
| title_fullStr | Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1S |
| title_full_unstemmed | Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1S |
| title_short | Suppression of Age-Related Macular Degeneration-like Pathology by c-Jun N-Terminal Kinase Inhibitor IQ-1S |
| title_sort | suppression of age related macular degeneration like pathology by c jun n terminal kinase inhibitor iq 1s |
| topic | age-related macular degeneration c-Jun N-Terminal Kinase Inhibitor IQ-1S OXYS rats |
| url | https://www.mdpi.com/2227-9059/11/2/395 |
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