Figure 3.

Overview of the complement components, regulators, and potential targets for inhibition. Selected complement components are depicted. All components except for MBL-associated serine protease-3 (MASP-3) [63] circulate in the blood as inactive components. Both the LP and the CP lead to the formation of C4b2a, a C3-convertase, while the alternative pathway (AP) comprises both a fluid-phase C3-convertase (C3(H₂O)Bb) and a surface-bound C3-convertase (C3bBb). The fluid-phase convertase is made when C3 is spontaneously hydrolyzed in plasma and binds factor B (FB), which is then cleaved by factor D (FD), while the surface-bound convertase requires preformed C3b on a surface that will bind FB, which is cleaved to FBb by FD. Properdin is a stabilizing regulator for the C3-convertases [64,65,66]. C3(H₂O) and C3b can be degraded into inactivated iC3(H₂O) and iC3b, respectively, by the enzyme factor I (FI) and a co-factor, such as factor H (FH). The targets of inhibition in wAMD clinical trials are indicated. AP, alternative pathway. CR1, complement receptor 1. FB, factor B. FD, factor D. FH, factor H. FI, factor I. MAC, membrane-attack complex. MASP, MBL-associated serine protease.