MESI is caused by immune dysregulation, leading to blood-retinal barrier breakdown and release of inflammatory mediators Yang et al. Int. J. Mol. Sci. 2023, 24: 4676. Metcalfe et al. Front. Immunol. 2020, 11: 1424. Shaik et al. Biomolecules. 2020, 10: 1673. Valle et al. Exp Eye Res. 2019, 178: 27. Mesquida et al. Trans Vis Sci Tech. 2019, 8: 32. Immune Trigger Blood-Retinal Barrier Breaks Down Causes immune cells to release pro-inflammatory cytokines, including IL-6 IL-6 upregulates VEGF. IL-6 and VEGF cause tight junction loss, allowing immune cells and blood plasma to leak into the retina IL-6 and VEGF Amplify Leakage VEGF promotes vascular leak and neovascularization, while IL-6 sustains inflammation and upregulates VEGF Leads to: BRB disrupted Leads to: Macular edema, visual impairment and worsening inflammation Together, IL-6 and VEGF compound the BRB damage 38