Protecting against AMD

Key Points

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world, estimated to affect approximately 497,000 people in the UK and the Republic of Ireland¹ and more than 1.75 million individuals in the United States; these figures are expected to double by 2020.² This increasing prevalence worldwide is largely attributable to increasing longevity and lifestyle changes associated with Western society.

Although the pathogenesis of AMD remains poorly understood, there is now a growing consensus that one or more of the following processes contribute to the condition: inflammation; oxidative stress; cumulative blue light damage; retinal pigment epithelial (RPE) cell dysfunction; and reduced foveolar choroidal circulation. It is generally agreed that oxidative stress and cumulative blue light damage are of major importance in AMD development.^3-5 Interestingly, both processes are compatible with every other hypothesized mechanism of AMD pathogenesis.

The importance of three carotenoids

This article specifically discusses the rationale and available evidence that supports the use of macular carotenoids in the prevention of AMD.

Oxidative stress explained

The hypothesis that oxygen, an essential requirement for all living organisms, is also a potentially toxic substance is becoming increasingly understood and accepted. Oxidative stress refers to damage caused by unstable and reactive oxygen intermediates (ROIs) and, as mentioned above, there is a growing body of evidence to suggest that damage caused by ROIs plays a role in the pathogenesis of AMD.

ROIs can be classified according to their reactivity towards biological targets, their site of production, their chemical nature, or their free radical or non-radical subgroups. In this article, we describe ROIs in terms of their free radical and non-radical subgroups.

Free radicals are molecules that contain one or more unpaired electrons in their outer orbits.⁷ In order to achieve a stable state, these unstable molecules 'steal' electrons from other molecules (e.g. lipids, proteins, DNA), which are themselves rendered unstable by this reaction, and a cascade of cytotoxic reactions ensues. Non-radicals, such as hydrogen peroxide, contain the full complement of electrons but are, nevertheless, in an unstable state. Antioxidants are molecules that neutralize ROIs; oxidative damage occurs, therefore, when the level of ROIs overwhelms the antioxidant defence system, with consequent cellular damage.⁷

The retina is particularly susceptible to damage by ROIs. There are several reasons for this vulnerability: firstly, there is an extremely high consumption of oxygen within the retina; secondly, the photoreceptors of the retina contain high amounts of polyunsaturated fatty acids (PUFAs). PUFAs are particularly susceptible to free radical damage because their conjugate double bonds are convenient sources of hydrogen atoms, which contain one electron. The retina is also exposed to visible light, which is known to generate ROIs via photosensitization reactions. Finally, the process of phagocytosis by the RPE is known to generate hydrogen peroxide (non-radical species).^7-10

Damaging blue light?

Cumulative (short-wavelength) blue light damage represents an environmental factor, which is believed to play a role in the pathogenesis of AMD. Over a lifetime, exposure to visible light (specifically, short-wavelength blue light) causes photo-oxidative damage to the retina,^4,5 and this damage is mediated through oxidative stress.⁸ Indeed, the presence of lipid peroxidation products following irradiation of the retina provides strong evidence that cumulative retinal light damage is mediated through ROIs.^3;11-14 It is generally accepted, therefore, that ROIs, generated by reactions involving short-wavelength irradiation and arterial oxygen, denature PUFAs in the photoreceptors, leading to cell death and AMD.