Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model.
Glaucoma is a leading cause of irreversible blindness. Injury of retinal ganglion cells (RGCs) accounts for visual impairment of glaucoma. Here, we report rapamycin protects RGCs from death in experimental glaucoma model and the underlying mechanisms. Our results showed that treatment with rapamycin...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4055719?pdf=render |
| _version_ | 1818947055561736192 |
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| author | Wenru Su Zuohong Li Yu Jia Yehong Zhuo |
| author_facet | Wenru Su Zuohong Li Yu Jia Yehong Zhuo |
| author_sort | Wenru Su |
| collection | DOAJ |
| description | Glaucoma is a leading cause of irreversible blindness. Injury of retinal ganglion cells (RGCs) accounts for visual impairment of glaucoma. Here, we report rapamycin protects RGCs from death in experimental glaucoma model and the underlying mechanisms. Our results showed that treatment with rapamycin dramatically promote RGCs survival in a rat chronic ocular hypertension model. This protective action appears to be attributable to inhibition of neurotoxic mediators release and/or direct suppression of RGC apoptosis. In support of this mechanism, in vitro, rapamycin significantly inhibits the production of NO, TNF-α in BV2 microglials by modulating NF-κB signaling. In experimental animals, treatment with rapamycin also dramatically inhibited the activation of microglials. In primary RGCs, rapamycin was capable of direct suppression the apoptosis of primary RGCs induced by glutamate. Mechanistically, rapamycin-mediated suppression of RGCs apoptosis is by sparing phosphorylation of Akt at a site critical for maintenance of its survival-promoting activity in cell and animal model. These results demonstrate that rapamycin is neuroprotective in experimental glaucoma, possibly via decreasing neurotoxic releasing and suppressing directly apoptosis of RGCs. |
| first_indexed | 2024-12-20T08:24:49Z |
| format | Article |
| id | doaj.art-303fd65b389a455188a344aac2751a83 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T08:24:49Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-303fd65b389a455188a344aac2751a832022-12-21T19:46:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0196e9971910.1371/journal.pone.0099719Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model.Wenru SuZuohong LiYu JiaYehong ZhuoGlaucoma is a leading cause of irreversible blindness. Injury of retinal ganglion cells (RGCs) accounts for visual impairment of glaucoma. Here, we report rapamycin protects RGCs from death in experimental glaucoma model and the underlying mechanisms. Our results showed that treatment with rapamycin dramatically promote RGCs survival in a rat chronic ocular hypertension model. This protective action appears to be attributable to inhibition of neurotoxic mediators release and/or direct suppression of RGC apoptosis. In support of this mechanism, in vitro, rapamycin significantly inhibits the production of NO, TNF-α in BV2 microglials by modulating NF-κB signaling. In experimental animals, treatment with rapamycin also dramatically inhibited the activation of microglials. In primary RGCs, rapamycin was capable of direct suppression the apoptosis of primary RGCs induced by glutamate. Mechanistically, rapamycin-mediated suppression of RGCs apoptosis is by sparing phosphorylation of Akt at a site critical for maintenance of its survival-promoting activity in cell and animal model. These results demonstrate that rapamycin is neuroprotective in experimental glaucoma, possibly via decreasing neurotoxic releasing and suppressing directly apoptosis of RGCs.http://europepmc.org/articles/PMC4055719?pdf=render |
| spellingShingle | Wenru Su Zuohong Li Yu Jia Yehong Zhuo Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model. PLoS ONE |
| title | Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model. |
| title_full | Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model. |
| title_fullStr | Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model. |
| title_full_unstemmed | Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model. |
| title_short | Rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model. |
| title_sort | rapamycin is neuroprotective in a rat chronic hypertensive glaucoma model |
| url | http://europepmc.org/articles/PMC4055719?pdf=render |
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