In collaboration with Wojciech Kedzierski, Ph.D., we have generated transgenic mouse lines expressing chimeric (part mouse/part human) Cfh molecules with either the 402-histidine (“at-risk”) variant or the 402-tyrosine (“non-risk”) variant of Cfh.
We aim to use these mice to: (a) identify the molecular basis for both the increased susceptibility to AMD and the resistance to therapy observed in human H-CFH carriers, and to (b) generate a relevant model of AMD that would allow the dissection of the role of the different arms of the immune system in the disease.
We have shown that our mice express the transgenic mRNA both in the liver and in the posterior segment ocular tissues. They also produce the transgenic protein, which can be found in the serum.
We are also using a laser-induced model of AMD as a way to study the acute neovascular phase of the disease. When applied to our transgenic mice it will help us determine if and how the factor H variants affect the susceptibility to neovascular changes, and the dependence of the neovascular membranes on VEGF and other growth factors.
This laser model is also helping us to examine the potential therapeutic role of some antibodies and small molecules generated here at UTSW in blocking or causing regression of choroidal neovascularization.