دورية أكاديمية
Aldose reductase inhibition decelerates optic nerve degeneration by alleviating retinal microglia activation
| العنوان: | Aldose reductase inhibition decelerates optic nerve degeneration by alleviating retinal microglia activation |
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| المؤلفون: | Mishal Rao, Yu-Kai Huang, Chia-Chun Liu, Chandler Meadows, Hui-Chun Cheng, Mengli Zhou, Yu-Chih Chen, Xin Xia, Jeffrey L. Goldberg, Andrew M. Williams, Takaaki Kuwajima, Kun-Che Chang |
| المصدر: | Scientific Reports, Vol 13, Iss 1, Pp 1-14 (2023) |
| بيانات النشر: | Nature Portfolio, 2023. |
| سنة النشر: | 2023 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract As part of the central nervous system (CNS), retinal ganglion cells (RGCs) and their axons are the only neurons in the retina that transmit visual signals from the eye to the brain via the optic nerve (ON). Unfortunately, they do not regenerate upon injury in mammals. In ON trauma, retinal microglia (RMG) become activated, inducing inflammatory responses and resulting in axon degeneration and RGC loss. Since aldose reductase (AR) is an inflammatory response mediator highly expressed in RMG, we investigated if pharmacological inhibition of AR can attenuate ocular inflammation and thereby promote RGC survival and axon regeneration after ON crush (ONC). In vitro, we discovered that Sorbinil, an AR inhibitor, attenuates BV2 microglia activation and migration in the lipopolysaccharide (LPS) and monocyte chemoattractant protein-1 (MCP-1) treatments. In vivo, Sorbinil suppressed ONC-induced Iba1 + microglia/macrophage infiltration in the retina and ON and promoted RGC survival. Moreover, Sorbinil restored RGC function and delayed axon degeneration one week after ONC. RNA sequencing data revealed that Sorbinil protects the retina from ONC-induced degeneration by suppressing inflammatory signaling. In summary, we report the first study demonstrating that AR inhibition transiently protects RGC and axon from degeneration, providing a potential therapeutic strategy for optic neuropathies. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-023-32702-5 |
| URL الوصول: | https://doaj.org/article/65c1f36d05de4c6aa38bd2db14f7b436 |
| رقم الأكسشن: | edsdoj.65c1f36d05de4c6aa38bd2db14f7b436 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-023-32702-5 |