Despite commonality between intracellular signaling for DRD4 and complement receptors, our data support a dominant role for C3aR1 and C5aR1 over DRD4 in inducing AMD cellular phenotypes in iRPE cells because blocking C3aR1 and C5aR1 is sufficient to rescue CC-HS induced TER drop and reduce APOE-positive deposits (Fig. 3i, j). Here, C3AR1 is linked to age-related macular degeneration.