SUMMARY Age-related macular degeneration (AMD) is the leading cause of vision loss in the Western World. The fundamental abnormalities occurring in retinal pigment epithelial (RPE) cells leading to their progressive dysfunction and eventually atrophy in AMD are not known. Multiple epidemiological, biochemical, and histological studies highlight the role of altered cholesterol metabolism in the pathogenesis of AMD. The liver x receptor is an important regulator of reverse cholesterol transport. Beyond this established function it has also been shown to regulate inflammation, cell metabolism and apoptosis. We have recently found that aged LXR knockout mice develop cardinal features of dry AMD including accumulation of cholesterol and neutral lipids within Bruch's membrane and development of significant sub-RPE deposits. Herein we propose to investigate the role of two modulators of LXR in RPE biology and pathogenesis of AMD.