MP is a blue-light absorbing yellow pigment containing the xanthophyll carotenoids, lutein, zeaxanthin and meso-zeaxanthin. In some people macular pigment prevents up to 95% of incident blue light wavelengths from reaching the outer retina. Macular pigment density can be regulated by diet, specifically by consumption of the carotenoids lutein and zeaxanthin. The amount of blue light reaching the outer retina is inversely proportional to macular pigment density. There is a growing consensus that an increased density of MP, and the corresponding reduction in blue light reaching the outer retina, results in a substantial delay in the onset of AMD.^{1, 1a}

As the layer of macular pigment is located in the inner retina, it is remote from the metabolic activities involved in the pathogenesis of AMD which occur in the outer retina. The generation of radical oxygen species(ROS) in RPE cells and the resulting increase in oxidative retinal stress in the outer retina is integral to the development of AMD. The primary mechanisms generating ROS in RPE cells are dependent upon, or substantially enhanced by, the absorption of blue light. Therefore increased absorption of sub-lethal amounts of blue light by RPE cells contributes to increased generation of ROS. When ROS levels exceed the RPE cell's antioxidative capacity, the result is increased levels of retinal oxidative stress and increased inducement of the inflammatory response.

The most obvious manner by which an increased density of MP can influence the development of AMD is through the reduction of ROS-generating blue light that reaches the outer retina, thus reducing the production of ROS and the retinal stress in that retinal region. However, because the retina is very thin in the region of the foveal pit, which is located near the center of the macula, and constituent macular carotenoid molecules have been found in photoreceptor cells in that region, some have posited that it is the increased levels of these carotenoid molecules, which do have strongly anti-oxidative properties, that give rise to the protective quality of increased macular pigment density. The possibility cannot yet be ruled out that of the multitude of endogenous and nutritional molecules that contribute to protection of the retina from oxidative stress, an increased number of carotenoid molecules in the macular pigment is a dominant protective factor.

With respect to the role of blue light in promoting the development of AMD, it is immaterial the extent to which the protection from AMD provided by increased macular pigment density results from limiting the amount of ROS-generating blue light that reaches the outer retina, or the extent ot which this protection results from the neutralization of radical oxygen species generated by the absorption of blue light in the outer retina. Increased oxidative retinal stress and the resulting chronic low grade inflammation in the outer retina is integral to the development of AMD.^2,3 Therefore, a measurable inverse relationship between macular pigment density and susceptibility to AMD establishes that blue light exposure contributes substantially to the development of AMD.

* Scientific inference can be used to establish a conclusion derived from logical deductions from valid premises. We propose that the following 4 premises are sufficient to establish that blue light exposure substantially advances the onset of AMD. Based on the considerable published evidence that supports each of these 4 statements, there appears to be a general consensus on the validity of these premises. Thus, while there are many gaps in the understanding of the pathogenesis of AMD, it can still be established that blue light exposure substantially contributes to the pathological development of this debilitating condition. The 4 premises are:
1) Chronic low grade inflammation in RPE cells is implicated in the pathogenesis of AMD.
2) The inflammatory response in the outer retina, which includes activation of the complement system, is induced by heightened levels of oxidative stress in the outer retina.
3) Light absorption contributes significantly to the generation of ROS in the outer retina. Blue light absorption (i.e. absorption of visible light with wavelengths shorter than 480 nm) is primarily responsible for photo-induced generation of ROS in the outer retina. This includes ROS generation within RPE cells resulting from absorption of light by mitochondria, nuclear DNA, lipofuscin, and remnants of photoreceptor cells, as well as by light absorption by photoreceptor remnants located in basal deposits and drusen adjacent to RPE cells and the Bruch’s membrane. Photic induction of ROS in the outer retina raises the level of oxidative stress in that region.
4) Macular pigment optical density (MPOD) is an independent risk factor for AMD. While the acceptance of this premise is not universal, and some are awaiting the confirmation of this by AREDS II, a large scale study which is seeking to establish the veracity of this premise, there appears to be a growing consensus amongst those researchers most actively examining the effects of increased MP density that this is now established, and that the determination of this reflects a substantial time difference (several years) between the development of AMD in people with high MPOD as compared with people with low MPOD.