Simvastatin inhibits ischemia/reperfusion injury-induced apoptosis of retinal cells via downregulation of the tumor necrosis factor-α/nuclear factor-κB pathway

Abstract

Simvastatin, which is widely used in the prevention and treatment of hyperlipidemia-associated diseases, has been reported to enhance the survival of retinal ganglion cells (RGCs) in a model of retinal ischemia/reperfusion (IR) injury. However, the underlying mechanism of the anti-apoptotic effects of simvastatin on the retina have yet to be elucidated. In the present study, rats were treated with simvastatin or saline for 7 days prior to IR via ligation of the right cephalic artery. The results showed that simvastatin prevented the apoptosis of RGCs and cells in the inner nuclear layer. Furthermore, simvastatin regulated the expression of apoptosis-associated proteins. The expression levels of the anti-apoptotic protein B-cell lymphoma-2 were upregulated 4 and 24 h after IR in the simvastatin/IR group compared to those in the saline/IR group. Conversely, the levels of pro-apoptotic protein Bax were downregulated in the simvastatin/IR group compared to those in the saline/IR group. Furthermore, the results of the present study showed for the first time, to the best of our knowledge, that simvastatin decreased IR injury-induced tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) expression in the retina. These findings strongly suggested that simvastatin inhibits apoptosis following IR-induced retinal injury by inhibition of the TNF-α/NF-κB pathway. The present study also provided a rationale for developing therapeutic methods to treat IR-induced retinal injury in the clinic.

PARP Inhibitor Protects Against Chronic Hypoxia/Reoxygenation-Induced Retinal Injury by Regulation of MAPKs, HIF1α, Nrf2, and NFκB

“…63 Most of the aforementioned cytokine and chemokine expressions were regulated by NFjB, which was reported to activate a number of cytokine and growth factor genes associated with ischemia-reperfusion injury in the retina. 64,65 NFjB is retained in the cytoplasm in an inactive form by its inhibitor, IjB, which is subjected to phosphorylation-mediated degradation. A number of signaling kinases, including MAPKs, phosphorylate and thereby activate IjB kinase.…”

Long Non-Coding RNA-MALAT1 Mediates Retinal Ganglion Cell Apoptosis Through the PI3K/Akt Signaling Pathway in Rats with Glaucoma

“…The major risk factor for glaucoma is elevated intraocular pressure (IOP) [2]; high IOP is a persistent trait determined by a mostly unknown complicated set of genetic and environmental causes [3]. According to medical studies of glaucoma, high IOP or retinal ischemia leads to constant RGC apoptosis [4, 5]. The present treatments for glaucoma are still aimed at reducing IOP, and while these treatments control IOP, they fail to prevent the progressive visual field loss of many glaucoma patients; surgical intervention for IOP control is also associated with a high incidence of graft failure [6, 7].…”

Tat-NOL3 protects against hippocampal neuronal cell death induced by oxidative stress through the regulation of apoptotic pathways

“…ROS production contributes to apoptotic cell death and DNA fragmentation after ischemia-reperfusion injury (38,39). Tat-NOL3 protein suppressed ROS-induced mitochondrial dysfunction in the HT22 cells.…”