Regulation of age-related macular degeneration-like pathology by complement factor H

• DOI: 10.1073/pnas.1424391112
• Publication Date: 2015-05-20T02:51:51Z
• Authors: Christopher B. To...; Una Kelly; Daniel R. Saban; Catherine Bowes R...
• Keywords: Choroid; Mice, Transgenic; Retinal Pigment Epithelium; Diet, High-Fat; Monocytes; Macular Degeneration; Mice; 03 medical and health sciences; 0302 clinical medicine; PNAS Plus; Complement Factor H; Animals

Significance

Age-related macular degeneration (AMD) affects approximately one-third of Americans over 70 and is characterized by lipoprotein-rich sub-retinal pigmented epithelium (sub-RPE) deposits. Substantial evidence has emerged that implicates complement factor H (CFH) in the pathogenesis of AMD. Here, we conduct an in vivo analysis to elucidate the role of CFH in AMD pathology. We show that ( i ) CFH and lipoproteins compete for binding in the sub-RPE extracellular matrix such that decreasing CFH leads to lipoprotein accumulation and sub-RPE deposit formation; and ( ii ) detrimental complement activation within sub-RPE deposits leads to RPE damage and vision loss. This new understanding of the complicated interactions of CFH in development of AMD-like pathology paves the way for identifying more targeted therapeutic strategies for AMD.