RTA408 alleviates retinal ganglion cells damage in mouse glaucoma by inhibiting excessive autophagy.

Background: Glaucoma, characterized by a high incidence and significant ocular harm, has been elucidated through various mechanisms. Excessive autophagy leading to the loss of retinal ganglion cells (RGCs) is suggested as one potential cause for visual impairment in glaucoma. Methods: A glaucoma model was established through anterior chamber injection of silicone oil in mice. RTA408 and the positive control tafluprost were administered for intervention. The efficacy was preliminarily assessed by intraocular pressure measurement. HE staining and fluorescent staining were used to assess RGC loss, while fluorescent staining and western blot were employed to evaluate the expression of Nrf2. The role of autophagy in the pathogenesis of glaucoma was investigated by artificially modulating autophagy levels. Results: In glaucomatous mice, RTA408 significantly reduces the apoptosis levels of RGCs and decreases RGC loss. Further investigations reveal a notable upregulation of autophagy levels in glaucomatous mice, with RGC loss being associated with autophagy. RTA408 promotes the expression of Nrf2 and downstream antioxidant molecules, enhancing the antioxidant system while downregulating mitochondrial autophagy levels. This reduces RGC apoptosis and loss, demonstrating a protective effect against glaucoma. Conclusion: Autophagy mediates the occurrence of glaucoma in mice, promoting RGC apoptosis. RTA408 alleviates RGCs damage by inhibiting excessive autophagy in the context of glaucoma. [ABSTRACT FROM AUTHOR]