Complement factor B is necessary for sub-RPE deposit formation in Efemp1R345W/R345W knock-in mice

Purpose: The EFEMP1 R345W mutation in humans causes Doyne honeycomb retinal dystrophy (DHRD), a disease with similar pathology to AMD. Efemp1 R345W/R345W knock-in mice (Efemp1 mice) develop deposits on the basal side of retinal pigment epithelial (RPE) cells, which are dependent on the presence of complement component C3. 1 The role of the alternative complement pathway component factor B (Cfb) was investigated in Efemp1 mice.Methods: Efemp1 mice were crossed with Cfb-/-mice. Eighteen month old wild type, Efemp1, Cfb-/-, and Efemp1: Cfb-/-mice were characterized for complement activation via Western blots, sub-RPE deposit formation via transmission electron microscopy, and tandem mass tag-based proteomic profiling (IQ Proteomics). Ten month-old female Efemp1 mice were dosed orally daily with a complement factor B inhibitor (compound 1) at 60 mg/kg for two months. The …