Lutein, zeaxanthin, and meso-zeaxanthin: The basic and clinical science underlying carotenoid-based nutritional interventions against ocular disease

Abstract

The human macula uniquely concentrates three carotenoids: lutein, zeaxanthin, and meso-zeaxanthin. Lutein and zeaxanthin must be obtained from dietary sources such as green leafy vegetables and orange and yellow fruits and vegetables, while meso-zeaxanthin is rarely found in diet and is believed to be formed at the macula by metabolic transformations of ingested carotenoids. Epidemiological studies and large-scale clinical trials such as AREDS2 have brought attention to the potential ocular health and functional benefits of these three xanthophyll carotenoids consumed through the diet or supplements, but the basic science and clinical research underlying recommendations for nutritional interventions against age-related macular degeneration and other eye diseases are underappreciated by clinicians and vision researchers alike. In this review article, we first examine the chemistry, biochemistry, biophysics, and physiology of these yellow pigments that are specifically concentrated in the macula lutea through the means of high-affinity binding proteins and specialized transport and metabolic proteins where they play important roles as short-wavelength (blue) light-absorbers and localized, efficient antioxidants in a region at high risk for light-induced oxidative stress. Next, we turn to clinical evidence supporting functional benefits of these carotenoids in normal eyes and for their potential protective actions against ocular disease from infancy to old age.

Keywords: Age-related macular degeneration; Carotenoid; Lutein; Macular pigment; Nutrition; Zeaxanthin.

Figure 1

Structure of the human fovea. Upper panel - In this section through the center of the fovea, the tightly packed cone cells in the center are evident. The rod cells are present in the periphery. The central region is devoid of inner limiting membrane, inner nuclear layer, and Henle's fibers. Figure adapted from a light microscopic anatomy of the fovea centralis in the eye of a 45-year-old woman (Yamada, 1969). os-outer segment, is- inner segment, om- outer limiting membrane, of-outer cone fiber, on-outer nuclear layer, oh-outer Henle's layer, in-inner nuclear layer, im-inner limiting membrane, g-ganglion cells, cp-capillary. Lower Panel - Representation of the anatomical details of primate fovea. RPE processes are present in between the photoreceptors. The RPE layer is separated from the choroid by the thin Bruch's membrane. Figure adapted from a schematic diagram by Snodderly to illustrate the anatomic and metabolic relation in the fovea of macaque retina (Snodderly, 1995).

Figure 2

Macular pigment levels in different parts of the eye (Bernstein, 2002).

Figure 3

The retinal distribution of macular pigment carotenoids and their binding proteins. (a) Vertical section (vitreous side down) through a monkey fovea showing the distribution of the yellow macular carotenoids. Image courtesy of Dr. Max Snodderly. (b) GSTP1 labeling of foveal cones in the macula of a 3-year-old monkey. This montage shows strongest labeling by antibody against GSTP1 (red) over the myoid and ellipsoid regions of cones identified by monoclonal antibody (7G6, green). (c) A low-magnification view of a near-foveal retina section in which N-62 StAR (red) identifies StARD3, an anti-cone arrestin monoclonal antibody (7G6, green) identifies monkey cones. The sections in (b) and (c) have the same orientation as in (a). Images courtesy of Dr. Jeanne M. Frederick.

Figure 4

Chemical structure of macular pigment carotenoids. (a),(b) Lutein; (c) zeaxanthin; (d) meso-zeaxanthin.

Figure 5

Protective roles of lutein and zeaxanthin, as an absorber of harmful light and as an antioxidant reacting with reactive oxygen species (ROS). *O₂, singlet oxygen; LOO^-, lipid peroxyl radicals ;LOOH, lipid peroxides.

Figure 6

Proposed pathway for formation of oxidative metabolites of lutein and zeaxanthin in human ocular tissues.

Figure 7

Industrial synthesis of commercial carotenoids.

Figure 8

Possible pathway for macular pigment carotenoid uptake, transport, and accumulation in the human retina.

Figure 9

Absorption Spectrum of macular pigment.

Figure 10

Image of macular pigment measured by Heidelberg Spectralis (Left, excitation wavelength at 488 nm; Right, excitation wavelength at 514 nm).

Figure 11

Autofluorescence technique, implemented by the Heidelberg Spectralis^® (HRA+OCT MultiColor) to produce a full spatial profile image of macular pigment optical density (MPOD).

Figure 12

Illustration of chromatic aberration in the normal eye.

Figure 13

Illustration showing the effect of light scatter on vision.

Figure 14

Anomalous macular pigment distributions in MacTel patients. Post-mortem specimen from a MacTel patient showing a circular distribution of yellow carotenoid pigment around the fovea (upper left); autofluorescence image of another MacTel patient with a hypofluorescent ring of macular pigment centered on the fovea (upper right); Heidelberg Spectralis macular pigment output from a third MacTel patient demonstrating absence of macular pigment at the fovea and a ring of macular pigment at 6 degrees eccentricity (approximately 1.7 mm) (bottom images).

Figure 15

RetCam reflectometry images of macular pigment in an infant eye. The left picture shows the RetCam device; the upper images present the raw blue light reflectance image, the blue channel output from the CCD chip, and the a fast Fourier transform (FFT) digital enhancement of the blue channel output; the bottom images show the digitally processed macular pigment data as a 3-D surface plot and as a line-scan through the fovea.