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Haksu Kyung, Vlad Bekerman, Jacky Man Kwong Kwong, Joseph Caprioli, Natik Piri; Celastrol Protects Retinal Ganglion Cells from Optic Nerve Crush but not from Glaucomatous Damage. Invest. Ophthalmol. Vis. Sci. 2013;54(15):430.
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© ARVO (1962-2015); The Authors (2016-present)
Celastrol, a triterpene extracted from Tripterygium wilfordii vine, has been used in traditional Chinese medicine as a remedy for inflammation and a variety of autoimmune diseases. It has been demonstrated to have neuroprotective properties in animal models of Parkinson's, Hungtington's, Alzheimer's diseases, and amyotrophic lateral sclerosis. Celastrol cell protective effects are associated with activation of heat shock and antioxidant cell stress pathways. This study evaluates celastrol retinal ganglion cell (RGC) protective effect after optic nerve crush (ONC) and intraocular pressure (IOP) elevation.
ONC and laser trabecular photocoagulation were performed on one eye of adult Brown Norway rats. Daily intraperitoneal(IP) (1mg/kg; for two or five weeks for ONC and experimental groups, respectively) or a single intravitreal(IVit) (0.2, 1 and 5 mg/kg; for ONC group) injections of Celastrol were administered. The extent of RGC degeneration was evaluated by determining the number of RGCs that were immunolabeled with Rbpms (RNA binding protein with multiple splicing) in a flat-mount retina. The retina was divided into superior, inferior and temporal quadrants and 3 sampling fields (0.32 x 0.24 mm) were collected at each region of 1, 2, and 3 mm from the optic nerve. The RGC number in 27 fields from each retina were counted and averaged.
RGC survival was evaluated two and five weeks after ONC and laser treatment, respectively. An IP injected Celastrol/No-ONC group showed an approximately 15.6% decrease in RGC numbers compared to Vehicle/No-ONC group (n=6, p=0.006). In the Vehicle/ONC group, RGCs loss was 90.4%, whereas in the Celastrol/ONC group 59.2% of the cells degenerated (n=6, p=0.004). In an IVit injected animals, 22.8% of RGCs survived in Vehicle/ONC group compared to 24.5, 36.8 and 43.9% of RGCs in animals treated with 0.2 (n=4, p=0.773), 1 (n=4, p=0.026) and 5 (n=4, p=0.039) mg/kg of Celastrol, respectively. In Celastrol treated Glaucoma, RGC loss was 56.1% of that of control animals (n=9, p<0.000). RGC loss in Vehicle/Glaucoma was 56.6% (n=10, p<0.000).
Both IP and IVit treatments with Celastrol support RGC survival in ONC model. In experimental glaucoma, the neuroprotective effect of this drug was not observed. This could be explained by differences in the nature of insults to RGCs that can subsequently activate alternate cell death pathways.
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