Bruch's Membrane Compartmentalizes Complement Regulation in the Eye with Implications for Therapeutic Design in Age-Related Macular Degeneration.

ABSTRACT: Age-related macular degeneration (AMD) is the leading cause of blindness in the western world and affects nearly 200 million people globally. Local inflammation driven by complement system dysregulation is currently a therapeutic target. Bruch's membrane (BrM) is a sheet of extracellular matrix that separates the retina from the underlying choroid, a highly vascularized layer that supplies oxygen and nutrition to the outer retina. Here, we show that most complement proteins are unable to diffuse through BrM, although FHL-1, factor D and C5a can. AMD-associated lipid deposition in BrM decreases FHL-1 diffusion. We show that this impermeability of BrM creates two separate semi-independent compartments with respect to complement activation and regulation. Complement proteins synthesized local

SUBMITTER: Clark SJ 

PROVIDER: S-EPMC5742201 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature