Work in Progress
- Does the H402 variant of Cfh predispose to increased risk for choroidal neovascularization (CNV) and/or resistance to anti-VEGF therapy?
Does H402 Cfh change the subretinal microenvironment predisposing to an altered activation of the immune system?
- Frequency and size of CNV induced by laser in H402 vs. Y 402 Cfh transgenic mice
- Response to anti-VEGF agents
Will the Cfh polymorphism lead to a mouse model of AMD with spontaneous CNV?
- Use high-throughput techniques (proteomics and custom-made qPCR array) to screen the
- subretinal tissues for levels of protein and mRNA of molecules of interest. Important
- molecules include: cytokines, chemokines and other chemoattractants, complement
- components, and enzymes involved in free-radical and lipofuscin methabolism.
Is the immune system involved in the pathogenesis of drusen or CNV? Are there subsets of inflammatory cells that are essential?
- Cross our transgenic mice with human c-reactive protein (hCrp) transgenic mice
- Look for histopathologic changes, clinically-visible drusen, pigmentary changes and CNV
- Triggers of inflammation/oxidative stress: light exposure
- Cross mice to Superoxide Dismutase 1 deficient mice to increase oxidative stress
Can our animal model help us identify novel molecules to inhibit the development of drusen or CNV?
- Analyze the deposition of complement, CRP and inflammatory molecules in the subretinal/sub-
- RPE space in our transgenic mice.
- Analyze the timing and type of cellular infiltration
- Deplete subsets of immune cells using antibodies