Complement Factor H Mutation W1206R Causes Retinal Thrombosis and Ischemic Retinopathy in Mice.

Complement Factor H Mutation W1206R Causes Retinal Thrombosis and Ischemic Retinopathy in Mice. Am J Pathol. 2019 Jan 31;: Authors: Song D, Ueda Y, Bhuyan R, Mohammed I, Miwa T, Gullipali D, Kim H, Zhou L, Song Y, Schultz H, Bargoud A, Dunaief JL, Song WC Abstract Single nucleotide polymorphisms and rare mutations in Factor H (FH; official name CFH) are associated with age-related macular degeneration and atypical hemolytic uremic syndrome, a form of thrombotic microangiopathy. Mice with the FH W1206R mutation (FHR/R) share features with human atypical hemolytic uremic syndrome. Here, we report that FHR/R mice exhibited retinal vascular occlusion and ischemia. Retinal fluorescein angiography demonstrated delayed perfusion and vascular leakage in FHR/R mice. Optical coherence tomography imaging of FHR/R mice showed retinal degeneration, edema, and detachment. Histological analysis of FHR/R mice revealed retinal thinning, vessel occlusion, as well as degeneration of photoreceptors and retinal pigment epithelium. Immunofluorescence showed albumin leakage from blood vessels into the neural retina and electron microscopy demonstrated vascular endothelial cell irregularity with narrowing of retinal and choroidal vessels. Knockout of C6, a component of the membrane attack complex, prevented the aforementioned retinal phenotype in FHR/R mice, consistent with membrane attack complex -mediated pathogenesis. Pharmacologic blockade of C5 also re...
Source: Am J Pathol - Category: Pathology Authors: Tags: Am J Pathol Source Type: research