Consequences of oxidative stress in age-related macular degeneration

Abstract

The retina resides in an environment that is primed for the generation of reactive oxygen species (ROS) and resultant oxidative damage. The retina is one of the highest oxygen-consuming tissues in the human body. The highest oxygen levels are found in the choroid, but this falls dramatically across the outermost retina, creating a large gradient of oxygen towards the retina and inner segments of the photoreceptors which contain high levels of polyunsaturated fatty acids. This micro-environment together with abundant photosensitizers, visible light exposure and a high energy demand supports a highly oxidative milieu. However, oxidative damage is normally minimized by the presence of a range of antioxidant and efficient repair systems. Unfortunately, as we age oxidative damage increases, antioxidant capacity decreases and the efficiency of reparative systems become impaired. The result is retinal dysfunction and cell loss leading to visual impairment. It appears that these age-related oxidative changes are a hallmark of early age-related macular degeneration (AMD) which, in combination with hereditary susceptibility and other retinal modifiers, can progress to the pathology and visual morbidity associated with advanced AMD. This review reassesses the consequences of oxidative stress in AMD and strategies for preventing or reversing oxidative damage in retinal tissues.

Figure 1

A diagram of a cross section of the eye showing major structures. An enlarged diagram of the neural retina, underlying RPE, choroid and sclera is shown on the right.

Figure 2

A diagram depicting the potential pathways leading from oxidative stress to retinal degeneration and AMD.