CD46 and age-related macular degeneration: Upregulation of the complement system found here is in line with previous results in models of dry AMD [13,32], and is in agreement with the finding that mice lacking of CD46, a membrane cofactor protein that plays a key role in the complement alternative pathway [33], demonstrate spontaneous age-related degenerative changes in the retina, RPE, and choroid that are consistent with the cardinal features of human AMD [34].