Ehrlich et al Figure 1 An illustration of the late form of AMD, showing the growth of the choroidal neovascularization from the choroicapillaris through the Bruch’s membrane into the subretinal space.These new vessels are abnormal and have a higher tendency of leakage and bleeding. Reprinted with permission from Bressler NM, Bressler SB, Fine SL 1988. Age-related macular degeneration. Surv Ophthalmol, 32:375–413. © 1998 Elsevier. have shown that the late stages of AMD are more common in whites than in other ethnic groups and that women are affected more than men (Hyman and Neborsky 2002). Nevertheless, the strongest, most consistent risk factors are smoking and age (Hyman and Neborsky 2002). Although aging will not inevitably lead to AMD development, there are changes with age that can predis- pose the eye to development of AMD. Primary senescence of retinal pigment epithelial cells and Bruch’s membrane can lead to accumulation of metabolic debris and drusen. Furthermore, primary abnormalities in ocular perfusion worsen with age, secondarily causing dysfunction of the retinal pigment epithelial cells, predisposing eyes to AMD. These anatomical changes together with an individual’s genetic make-up and environmental risk factors set the stage for the development of AMD (Ciulla et al 2001). In this report, we focus on the role that aging plays in the pathogenesis of AMD. We start from a structural approach with alterations in the retinal pigment epithelium-Bruch’s membrane-choriocapillaris complex. Then we focus on the vascular changes with an attention to ocular blood 474 ﬂow alterations that correlate with AMD lesion development. Finally, we discuss the role of genetics in development of AMD. Structural changes with age and in AMD The outer retina is made up of the retinal pigment epithelium and photoreceptors. The retinal pigment epithelial cells form the outer blood-retinal barrier to facilitate selective transport between the choroidal blood vessels and the outer retina (Salvi et al 2006). Therefore, they play a major role in rod and cone photoreceptor integrity. The retinal pigment epithelium is a phagocytic system that is essential to the renewal of photoreceptors (de Jong 2006). When the tips (or outer segments) of photoreceptors are shed, retinal pigment epithelial cells have been shown to engulf and to degrade its components (de Jong 2006). Burns and Feeney- Burns (1980) speculate that the retinal pigment epithelium then transports the engulfed cytoplasmic material through Bruch’s membrane into the choriocapillaries. Age-related processes that occur in the retinal pigment epithelium-Bruch’s membrane-choriocapillaris complex Clinical Interventions in Aging 2008:3(3)