*2.3.2 Transgenic CFH Y402H mice*

The CFH Y402H polymorphism causes chronic inflammation by disrupting the binding of CFH to C-reactive protein and heparan sulfate [26]. At one year of age, transgenic mice with this polymorphism were found to have more drusen-like deposits compared to wild-type or *Cfh*−/− mice [17]. The CFH Y402H mice also exhibited thickening of BrM and increased accumulation of immune cells and complement in the subretinal space and basement membrane, respectively. Unlike *Cfh*−/− mice, CFH Y402H mice did not show photoreceptor atrophy possibly because the mice studied were younger by one year of age or from retaining partial functionality of CFH [17].

#### *2.3.3 Transgenic mice overexpressing C3*

Implied by the regulation of C3b through CFH, C3 plays an important activating role in complement pathways. Transgenic mice transduced using adenovirus expressing C3 have higher levels of C3 and a pathology similar to AMD including loss of photoreceptor outer segments and RPE, along with the accumulation of complement. Another finding in these mice was the migration and proliferation of endothelial cells in the retina which may correspond to RAP documented in patients with exudative AMD. However, this model is limited because these mice also exhibit retinal detachments, which are not seen in AMD. It is possible that the injected adenovirus may contribute to some of the unexpected retinal changes [17].
