VTN and age-related macular degeneration: Furthermore, the complement proteins present in RPE-released EVs were shown to increase in the presence of AMD-relevant stressors (e.g., C3, C4A, C4B) and accumulate in the drusen or ECM beneath the RPE monolayer (Wang et al., 2009a; 2009b; Klingeborn et al., 2017; Flores-Bellver et al., 2021).