Age-related macular degeneration and the aging eye

Abstract

Age-related macular degeneration (AMD) is an ocular disease that causes damage to the retinal macula, mostly in the elderly. Normal aging processes can lead to structural and blood flow changes that can predispose patients to AMD, although advanced age does not inevitably cause AMD. In this review, we describe changes that occur in the macular structure, such as the retinal pigment epithelium and Bruch's membrane, with advancing age and in AMD. The role of genetics in AMD and age-related changes in ocular blood flow that may play a role in the pathogenesis of AMD are also discussed. Understanding the pathophysiology of AMD development can help guide future research to further comprehend this disease and to develop better treatments to prevent its irreversible central vision loss in the elderly.

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.

Figure 2

The vascular and nonvascular theory of AMD. The vascular theory, suggested by Friedman (1997), states that with increased resistance in the choroidal vessels, there is an increase in the osmotic gradient against which the retinal pigment epithelial cells must pump. This leads to retinal pigment epithelial cell dysfunction and the accumulation of metabolic debris and drusen formation. Furthermore, the decrease in choroidal perfusion causes ischemic/hypoxic injury and increased oxidative stress, which can signal choroidal neovascularization formation. On the other hand, in the nonvascular theory, senescent retinal pigment epithelial cells can lead to retinal pigment epithelial cell dysfunction, which in turn can cause choriocapillary atrophy. Over time, and individual’s genetic predisposition and environmental stressors in the setting of structural and vascular changes make the eye more susceptible to AMD development.