Salvianolic Acid a Protects Optic Nerve from Ischemia–Reperfusion Injury <i>via</i> Inhibiting Astrocytes and ROCK Activation

Abstract

Backgrounds: Ischemia/Reperfusion (I/R) injury induces apoptosis of retinal ganglion cells (RGCs) and optic nerve, which supposed to be mechanism of acute high IOP in glaucoma. Salvianolic Acid A is a potent natural anti- I/R monomer while little is known about its neuro-protecting effects. The present study was performed to investigate the underlying mechanism of Sal A in alleviating I/R injury, especially focusing on astrocytes inactivation and Rho-kinase inhibition. Methods: SD mice were divided into 3 groups: Control, I/R and I/R+Sal A group. A 60-min ischemic model was administered by raising the IOP, followed by a reperfusion period till 3 weeks. Retina and optic nerve morphology, RGC apoptosis and glial cells activation were detected, the underlying neuro-protective mechanisms of Sal A were also explored. Results: Sal A attenuated I/R injury by reducing RGC apoptosis and optic nerve degeneration. I/R activated astrocytes ,reduced βⅢ-Tubulin expression and retina thickness, which were also antagonized by Sal A.Meanwhile Sal A prohibits I/R-induced optic nerve degeneration via inactivating mapk and Rock1/2. Conclusions: The above results suggested that Sal A prohibits glaucomatous neuropathy induced by I/R injury and is indicative of potential drug activity. Funding Statement: This work was supported by Chinese National Natural Science Foundation (81674027). Declaration of Interests: The authors report no conflicts of interest. Ethics Approval Statement: This study was approved by the institutional Animal Care and Use Committee (IACUC) at the medical academy of Shanghai Jiao Tong University. All animal experiments were performed in accordance with the guidelines of the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research.