دورية أكاديمية
In vitro and in vivo neuroprotective effects of cJun N-terminal kinase inhibitors on retinal ganglion cells
| العنوان: | In vitro and in vivo neuroprotective effects of cJun N-terminal kinase inhibitors on retinal ganglion cells |
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| المؤلفون: | Kim, Byung-Jin, Silverman, Sean M., Liu, Yang, Wordinger, Robert J., Pang, Iok-Hou, Clark, Abbot F. |
| المصدر: | Molecular Neurodegeneration |
| بيانات النشر: | BioMed Central Ltd. |
| سنة النشر: | 2022 |
| المجموعة: | UNTHSC Scholarly Repository (University. of North Texas Health Science Center) |
| مصطلحات موضوعية: | Electroretinography, JNK inhibitors, Retinal ganglion cells, Retinal ischemia, c-Jun N-terminal kinase (JNK), Animals, Anthracenes / pharmacology, Apoptosis / drug effects, Disease Models, Animal, Female, Intraocular Pressure / physiology, JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors, JNK Mitogen-Activated Protein Kinases / metabolism, Neuroprotective Agents / pharmacology, Rats, Sprague-Dawley, Reperfusion Injury / metabolism, Retina / metabolism, Retinal Diseases / metabolism, Retinal Ganglion Cells / metabolism |
| الوصف: | BACKGROUND: The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in neuronal pathophysiology. Using JNK inhibitors, we examined involvement of the JNK pathway in cultured rat retinal ganglion cell (RGC) death and in mouse retinal ischemia/reperfusion (I/R) injury of the visual axis. The in vitro effects of JNK inhibitors were evaluated in cultured adult rat retinal cells enriched in RGCs. Retinal I/R was induced in C57BL/6J mice through elevation of intraocular pressure to 120 mmHg for 60 min followed by reperfusion. SP600125 was administered intraperitoneally once daily for 28 days. Phosphorylation of JNK and c-Jun in the retina was examined by immunoblotting and immunohistochemistry. The thickness of retinal layers and cell numbers in the ganglion cell layer (GCL) were examined using H&E stained retinal cross sections and spectral domain optical coherence tomography (SD-OCT). Retinal function was measured by scotopic flash electroretinography (ERG). Volumetric measurement of the superior colliculus (SC) as well as VGLUT2 and PSD95 expression were studied. RESULTS: JNK inhibitors SP600125 and TAT-JNK-III, dose-dependently and significantly (p < 0.05) protected against glutamate excitotoxicity and trophic factor withdrawal induced RGC death in culture. In the I/R model, phosphorylation of JNK (pJNK) in the retina was significantly (p < 0.05) increased after injury. I/R injury significantly (p < 0.05) decreased the thickness of retinal layers, including the whole retina, inner plexiform layer, and inner nuclear layer and cell numbers in the GCL. Administration of SP600125 for 28 days protected against all these degenerative morphological changes (p < 0.05). In addition, SP600125 significantly (p < 0.05) protected against I/R-induced reduction in scotopic ERG b-wave amplitude at 3, 7, 14, 21 and 28 days after injury. SP600125 also protected against the I/R-induced losses in volume and levels of synaptic markers in the SC. Moreover, the protective effects of SP600125 in the ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | unknown |
| تدمد: | 1750-1326 |
| العلاقة: | https://doi.org/10.1186/s13024-016-0093-4Test; Kim, B. J., Silverman, S. M., Liu, Y., Wordinger, R. J., Pang, I. H., & Clark, A. F. (2016). In vitro and in vivo neuroprotective effects of cJun N-terminal kinase inhibitors on retinal ganglion cells. Molecular neurodegeneration, 11, 30. https://doi.org/10.1186/s13024-016-0093-4Test; https://hdl.handle.net/20.500.12503/31729Test; 11 |
| الإتاحة: | https://doi.org/20.500.12503/31729Test https://doi.org/10.1186/s13024-016-0093-4Test https://hdl.handle.net/20.500.12503/31729Test |
| حقوق: | Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0Test/ ; © 2016 Kim et al. |
| رقم الانضمام: | edsbas.75F46995 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 17501326 |
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