AMD is the leading cause of blindness in the developed world. Its incidence is increasing as the elderly population expands. It is characterised by the progressive destruction of the retinas central region (macula), causing central field visual loss and formation of extracellular deposits called drusen. These drusen are concentrated in and around the macula behind the retina between the retinal pigment epithelium (RPE) and the choroid. Although the etiology of AMD remains unclear, possible risk factors include age, ethnicity, smoking, hypertension, obesity and diet.

Visual distortion in Age-related macular degeneration

Normal	Advanced AMD

FH has been implicated with AMD through the observation of a Tyr402His polymorphism in SCR-7 in affected patients. The allele frequencies were found to be 54% for tyrosine and 46% for histidine from a control population, however 94% of AMD cases were found to have the histidine allele. This polymorphism has also been previously identified in HUS patients, but was not associated with the disease as it was seen in both patients and controls. The homology model of SCR-7 shows His402 to be on a surface exposed loop in close proximity to positively charged exposed residues Arg404 and Lys405. FH constructs in which both Arg404 and Lys405 are replaced with uncharged alanine residues showed reduced binding to heparin, C-reactive protein (CRP) and M protein, indicating these residues are important for binding. The change between tyrosine and histidine in close proximity to these residues could inhibit heparin binding and lead to a dysfunctional FH molecule.