Subretinal infiltration of monocyte derived cells and complement misregulation in mice with AMD-like pathology

Abstract

We have characterized a naturally-occurring mutation in mice that causes slow, progressive photoreceptor degeneration, white fundus flecks, and late-onset RPE atrophy. These animals predictably lose visual function as photoreceptors degenerate. Genetic studies identified a deletion in the 5’ coding sequence of Mfrp, designated Mfrp 174delG, which essentially results in a complete knockout at the protein level. We have shown in Mfrp 174delG mice that these white fundus flecks are due to the presence of F4/80+ inflammatory cells in the subretinal space. Here we expand on our initial description of the cells with additional markers and by determining their origin. We have also begun an analysis of complement factors in the RPE and found decreased levels of C3d, suggesting that the alternative complement pathway may be misregulated. Finally, we compare and contrast the characteristics of fundus images in Mfrp 174delG mice with those of other mutations that cause similar irregularities, including Crb1 rd8 and RDH5, and discuss the structural differences that may underlie them.