Biochemical Characterisation of the C1QTNF5 Gene Associated with Late-Onset Retinal Degeneration

Age-related macular degeneration (AMD) is the commonest cause of severe vision loss in adults, affecting up to 30% of the elderly population and accounting for 50–60% of new blind registration in western countries (Green and Enger, 1993; Seddon, 2001). It is characterised by a late-onset degeneration of the retinal macula and represents the advanced stage of a more common disorder, age-related maculopathy. There are two clinical subtypes of AMD, one is a “dry” form characterised by geographic atrophy, the other a “wet” form characterised by choroidal neovascularisation (CNV). This “wet” form represents only 10% of cases but accounts for about 90% of registered blindness (Ferris et al., 1984). The important early pathological features of AMD are the presence of both focal (drusen) and diffuse extracellular (basal) deposits in the macula, between the retinal pigment epithelium (RPE) and inner collagenous layer of Bruch’s membrane, a pentalaminar structure bounded by the basement membranes of RPE and choroidal capillary 1endothelium. These deposits lead to dysfunction and later death of RPE and associated photoreceptors. The nature of the proteins within the diffuse extracellular deposits have not been elucidated but the focal deposits (drusen) include >100 proteins, together with esterified and non-esterified cholesterol and other lipids and glycosaminoglycans (Crabb et al., 2002; Malek et al., 2003). Risk factors for AMD include age, sex, family history, APOE genotype, smoking, ethnicity and cardiovascular disease (Seddon, 2001). Genetic factors are implicated in AMD on the basis of twin and family studies but it appears to be a genetically complex disorder (Hammond et al., 2002).