title: 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.
authors.affiliation: Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, 53226, Milwaukee, WI, USA, jfogerty@mcw.edu.
authors.forename: Joseph
authors.initials: J
authors.lastname: Fogerty
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Besharse
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics; D000818:Animals; D016026:Bone Marrow Transplantation; D003170:Complement Pathway, Alternative / Q000276:immunology; D003165:Complement System Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics; D057092:Geographic Atrophy / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008268:Macular Degeneration / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics; D012160:Retina / Q000276:immunology / Q000473:pathology; D000099274:Frizzled-Related Proteins
chemical_list: D000429:Alcohol Oxidoreductases; D003165:Complement System Proteins; D005136:Eye Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C453730:Crb1 protein, mouse; C423368:Mfrp protein, mouse; D000099274:Frizzled-Related Proteins; C105846:retinol dehydrogenase 5