Initial Observations of Key Features of Age-Related Macular Degeneration in APOE Targeted Replacement Mice

Abstract

Age-related macular degeneration (AMD) is a late-onset, neurodegenerative disease of the retina and is the leading cause of catastrophic vision loss in the elderly. AMD usually occurs in people over the age of 65 years (Javitt et al., 2003) and accounts for approximately 50% of registered blindness in Western Europe and North America (Mitchell et al., 1998; Vingerling et al., 1995a). It develops as either dry AMD, geographic atrophy, or wet AMD (exudative) (Bird et al., 1995; Green, 1999). Dry AMD is characterized by the presence of sub-retinal pigment epithelium (RPE) deposits including drusen, basal linear deposits and basal laminar deposits (Curcio and Millican, 1999; Sarks, 1976). Geographic atrophy is characterized by RPE atrophy and wet or exudative AMD is characterized by choroidal neovascularization (CNV) (1991) and more recently, retinal angiomatous proliferation (Yannuzzi et al., 2001). In AMD with CNV, tufts of newly formed, functionally incompetent, blood vessels proliferate from the choroid, break through a thickened and fragile Bruch’s membrane (Grossniklaus and Green, 2004), and extend laterally into the sub-RPE (Sarks et al., 1980; Tobe et al., 1998a). These vessels in turn, may erode through the RPE, infiltrate the neural sensory retina, and communicate with the retinal circulation in what has been referred to as a retinal-choroidal anastomosis. This is common in the end stage of disciform disease (Yannuzzi et al., 2001).