sirolimus and Optic-Nerve-Diseases

p62, which is also called sequestosome 1 (SQSTM1), plays a critical role in neuronal cell death. However, the role of p62 in axonal degeneration remains unclear. We evaluated whether the modulation of p62 expression may affect axonal loss in tumor necrosis factor (TNF)-induced optic nerve degeneration. Immunoblot analysis showed that p62 was upregulated in the optic nerve after intravitreal injection of TNF. Treatment with p62 small interfering RNA (siRNA) exerted a partial but significant protective effect against TNF-induced axonal loss. Rapamycin exerted substantial axonal protection after TNF injection. We found that the increase in p62 was significantly inhibited by p62 siRNA. Treatment with rapamycin also significantly inhibited increased p62 protein levels induced by TNF. These results suggest that the upregulation of p62 may be involved in TNF-induced axonal degeneration and that decreased p62 levels may lead to axonal protection.

Topics: Animals; Axons; Heat-Shock Proteins; Male; Nerve Degeneration; Neuroprotective Agents; Optic Nerve Diseases; Rats, Wistar; Sequestosome-1 Protein; Sirolimus; Tumor Necrosis Factor-alpha

Topics: Everolimus; Female; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Kidney Transplantation; Middle Aged; Optic Nerve Diseases; Posterior Leukoencephalopathy Syndrome; Postoperative Complications; Sirolimus; Vision, Ocular

Topics: Evoked Potentials, Visual; Female; Humans; Immunosuppressive Agents; Middle Aged; Optic Nerve Diseases; Pancreas Transplantation; Sirolimus; Tacrolimus; Visual Acuity