Investigation of the capacity of a diet rich in lutein and zeaxanthin (from selected Capsicum varieties) to increase macular pigment density

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AMD is the leading cause of blindness in developed countries. In early AMD, waste material - drusen -builds up under the retina, the light-detecting layer in the eye. Increasing size and number of drusen is associated with development of the late forms of AMD: geographic atrophy (GA) where there is gradual death of light-detecting cells and neovascular AMD (nAMD) where fragile blood vessels grow below and into the retina, causing bleeding. Both types lead to permanent vision loss and can occur together. Currently, the only effective treatment for nAMD is eye injections that help reduce vision loss. No known treatments prevent the development of GA. The macula is a specialised part of the retina, mediating central vision, providing the sharpest visual acuity and facilitating the best colour-discrimination (Ma et al. Nutrients 2016). Macular pigment, measured by macular pigment optical density (MPOD), is concentrated in the inner and central layers and is believed to protect against AMD. It is mainly composed of the xanthophylls, lutein, zeaxanthin and meso-zeaxanthin (synthesised in situ from lutein). The concentration of these xanthophylls in the macula is 1000-fold greater than in the blood, demonstrating high selectivity. These xanthophylls are thus believed to play a major role in protecting the retina and retinal pigment epithelium from light-initiated oxidative damage by scavenging reactive oxygen species and filtering blue light. The xanthophylls are transported on HDL and polymorphisms in HDL-related loci have been associated with AMD and serum lutein/zeaxanthin. Data from epidemiological studies suggest that dietary xanthophyll intake is inversely associated with AMD risk. The AREDS2 randomised trial, carried out in the US, supplemented patients with early AMD with an antioxidant supplement that included lutein (10mg) and eaxanthin (2mg). In a secondary analysis of that study, supplementation with lutein/zeaxanthin was protective against progression to late AMD in individuals with low lutein/zeaxanthin intake (Chew et al. JAMA Opthalmol 2014). A 2016 metaanalysis of 19 studies (Ma et al.) showed that lutein, zeaxanthin and meso-zeaxanthin supplementation improved MPOD both in AMD patients and healthy subjects, with a dose-response relationship. However, not all studies have shown an effect of lutein/zeaxanthin supplements on MPOD (Korobelnik et al. JAMA Ophthalmol 2017; Lin et al. Opthalmic Epidemiol 2017). The proposed research will address that uncertainty (see Section 1c).