Characterization of CFH and the Alternate Complement Pathway in Models for Age Related Macular Degeneration

Document Type


Publication Date

Summer 2019

JAX Location

In: Student Reports, Summer 2019, The Jackson Laboratory


tA:_g e-related macular degeneration (AMD) is the leading cause of blindness in Americans over 50 years of age. One of the hallmark characteristics of the disease is the accumulation oflipids and protein deposits called drusen in the sub-RPE layer. Complement factor H (CFH), a protein whose primary function is regulating genes in the alternative complement pathway, and ARMS2, a gene of unknown function that has been implicated in AMD in humans, are of interest to us. To examine whether human C'FH and ARMS2 variants have a molecular and pathological consequence in the mouse posterior eye~ we used CRISPR/Cas9 genome editing to create mouse models bearing these human AMD allelic variants. We performed biochemical and western blot analysis on these variants, and found a down-regulation of proteins in the alternative complement pathway. By TEM analysis, we observed that both Cfh-and ARMS2 variants recapitulated some of the RPE pathologies observed in patients with AMD. Studying murine models of AMD will help us decipher the molecular and pathophysiological mechanisms that lead to AMD. It may also lead to improved therapeutic strategies for treating patients with specific AMD alleles.

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