Study on the Protective Effects and Mechanisms of Atorvastatin in Retinal Ischemia-Reperfusion Injury in Mice

Abstract

Retinal ischemia-reperfusion injury (RIRI) is a major cause of visual impairment, with limited effective treatment options. Atorvastatin (Ato), recognized for its pleiotropic effects, has demonstrated potential neuroprotective and vasculoprotective properties. This study aimed to evaluate the protective effects of Ato in a murine RIRI model and elucidate its underlying molecular mechanisms. An RIRI model was established via anterior chamber saline perfusion. Retinal ganglion cell (RGC) survival, superficial vascular density, morphology, and function were assessed, identifying 7 days post-injury as the optimal time point for model evaluation. Subsequent oral Ato administration significantly preserved RGCs, vascular density, and retinal function compared to the untreated RIRI group. Transcriptomic analysis identified insulin-like growth factor 1 (IGF1) as a key differentially expressed gene following Ato treatment. KEGG pathway enrichment analysis suggested IGF1 involvement in the Mitogen-Activated Protein Kinase (MAPK) signaling pathway. qRT-PCR, Western blotting, and immunofluorescence confirmed upregulated IGF1 expression in Ato-treated mice. These findings indicate that Ato may confer neurovascular protection against RIRI by sustaining IGF1/IGF1R expression, potentially engaging downstream MAPK pathways, thereby preserving retinal neurons, vascular integrity, and visual function.