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PURPOSE To compare action spectra for visual discomfort in the fovea and the parafovea and to determine the effect of macular pigment (MP). METHODS Visual discomfort thresholds to lights from 440 to 600 nm were obtained for six young (

Purpose To investigate genetic determinants of macular pigment optical density in women from the Carotenoids in Age-Related Eye Disease Study (CAREDS), an ancillary study of the Women's Health Initiative Observational Study. Methods 1585 of 2005 CAREDS participants had macular pigment optical density (MPOD) measured noninvasively using customized heterochromatic flicker photometry and blood samples genotyped for 440 single nucleotide polymorphisms (SNPs) in 26 candidate genes related to absorption, transport, binding, and cleavage of carotenoids directly, or via lipid transport. SNPs were individually tested for associations with MPOD using least-squares linear regression. Results Twenty-one SNPs from 11 genes were associated with MPOD (P ≤ 0.05) after adjusting for dietary intake of lutein and zeaxanthin. This includes variants in or near genes related to zeaxanthin binding in the macula (GSTP1), carotenoid cleavage (BCMO1), cholesterol transport or uptake (SCARB1, ABCA1, ABCG5, and LIPC), long-chain omega-3 fatty acid status (ELOVL2, FADS1, and FADS2), and various maculopathies (ALDH3A2 and RPE65). The strongest association was for rs11645428 near BCMO1 (βA = 0.029, P = 2.2 × 10(-4)). Conditional modeling within genes and further adjustment for other predictors of MPOD, including waist circumference, diabetes, and dietary intake of fiber, resulted in 13 SNPs from 10 genes maintaining independent association with MPOD. Variation in these single gene polymorphisms accounted for 5% of the variability in MPOD (P = 3.5 × 10(-11)). Conclusions Our results support that MPOD is a multi-factorial phenotype associated with variation in genes related to carotenoid transport, uptake, and metabolism, independent of known dietary and health influences on MPOD.

In natural vision, continuously changing input is generated by fast saccadic eye movements and slow drifts. We analyzed effects of fixational saccades, voluntary saccades, and drifts on the activity of macaque V1 neurons. Effects of fixational saccades and small voluntary saccades were equivalent. In the presence of a near-optimal stimulus, separate populations of neurons fired transient bursts after saccades, sustained discharges during drifts, or both. Strength, time course, and selectivity of activation by fast and slow eye movements were strongly correlated with responses to flashed or to externally moved stimuli. These neuronal properties support complementary functions for post-saccadic bursts and drift responses. Local post-saccadic bursts signal rapid motion or abrupt change of potentially salient stimuli within the receptive field; widespread synchronized bursts signal occurrence of a saccade. Sustained firing during drifts conveys more specific information about location and contrast of small spatial features that contribute to perception of fine detail. In addition to stimulus-driven responses, biphasic extraretinal modulation accompanying saccades was identified in one third of the cells. Brief perisaccadic suppression was followed by stronger and longer-lasting enhancement that could bias perception in favor of saccade targets. These diverse patterns of neuronal activation underlie the dynamic encoding of our visual world.

PURPOSE Macular pigment (MP) is composed of two dietary carotenoids, lutein and zeaxanthin, and a carotenoid generated by the retina, meso-zeaxanthin. There is large intersubject variability in peak optical density, spatial profile, and lateral extent of macular pigment, and it has been suggested that foveal architecture may play a role in this variability. This study is an initial investigation of the relationship between the spatial profile of macular pigment and foveal architecture. METHODS Sixty normal subjects were enrolled (one was eventually excluded). The spatial profile of macular pigment optical density (MPOD) was measured by customized heterochromatic flicker photometry (cHFP). High-resolution macular thickness maps were obtained by optical coherence tomography. Four parameters were analyzed: (1) minimum foveal thickness (MFT) at the intersection of six radial scans; (2) central foveal thickness (CFT) averaged over the central 1 mm of the fovea; (3) foveal width identified as the region lacking a nerve fiber layer; and (4) foveal width measured from crest to crest. Lifestyle and vision information were obtained by questionnaire. RESULTS The mean +/- SD MPOD at 0.25 degrees eccentricity was 0.49 +/- 0.23 and at 0.5 degrees eccentricity, 0.41 +/- 0.21. A first-order decreasing exponential function accounted for most of the variance of the MP profile averaged across subjects (r(2) = 0.99). MPOD measured at 0.25 degrees was unrelated to both measures of foveal thickness for the entire study group (r = 0.03, P = 0.81, and r = -0.08, P = 0.57, respectively). Similarly, MPOD measured at 0.5 degrees was unrelated to foveal thickness in the entire study group (r = 0.12, P = 0.36 and r = -0.05, P = 0.71, respectively). However, when analyzed separately in the nonwhite subjects, the relationship between MPOD at 0.25 degrees and MFT was positive and significant (r = 0.59, P = 0.01), but remained unrelated to CFT (r = 0.20, P = 0.41). Similarly, in the nonwhite subjects, the relationship between MPOD at 0.5 degrees and MFT was positive and significant (r = 0.68, P < 0.01), but again was unrelated to CFT (r = 0.23, P = 0.32). There was no significant relationship between MPOD and either measure of foveal thickness in the white subjects. In the entire study group, there was a positive and significant relationship between foveal width and MPOD averaged across the fovea (r = 0.41, P < 0.01) and between foveal width and MP integrated across the fovea (r = 0.41, P < 0.01). CONCLUSIONS Foveal MP was positively and significantly related to foveal width in the entire study group. This relationship may be determined by the greater length of the cone axons (Henle fibers) in wider foveas. MPOD was unrelated to foveal thickness in the white subjects. However, in the nonwhite subjects there was a positive association between MFT and MPOD at the 0.25 degrees and 0.5 degrees eccentricities, suggesting that other personal characteristics modulate the MPOD-retinal thickness relationship.

PURPOSE. Macular pigment (MP) is composed of the xanthophylls lutein (L) and zeaxanthin (Z) and may help to prevent age-related macular degeneration or retard its progression. In this study the effects of L or Z supplementation on carotenoid levels was examined in serum, adipose tissue, and retina in rhesus monkeys with no previous intake of xanthophylls. METHODS. From birth to 7 to 16 years of age, 18 rhesus monkeys were fed semipurified diets containing all essential nutrients but no xanthophylls. Six were supplemented with pure L and 6 with pure Z at 3.9 mol/kg per day for 24 to 101 weeks. At baseline and at 4- to 12-week intervals, carotenoids in adipose tissue were measured by HPLC. At study completion, carotenoids in serum and retina (central 4 mm, 8-mm annulus, and the periphery) were determined. Results were compared with data from control monkeys fed a standard laboratory diet. RESULTS. Monkeys fed xanthophyll-free diets had no L or Z in serum or tissues. After L or Z supplementation, serum and adipose tissue concentrations significantly increased in the supplemented groups. Both L and 3R,3S-Z (RSZ or meso-Z, not present in the diet) were incorporated into retinas of monkeys supplemented with L, with RSZ present only in the macula (central 4 mm). All-trans Z, but no RSZ, accumulated in retinas of monkeys supplemented with Z. CONCLUSIONS. L is the precursor of RSZ, a major component of macular pigment. Xanthophyll-free monkeys can accumulate retinal xanthophylls and provide a valuable model for examining their uptake and conversion. (Invest Ophthalmol Vis Sci. 2005;46:692‐702) DOI:10.1167/iovs.02-1192

PURPOSE. To study the effects of age and of n–3 fatty acids, lutein, and zeaxanthin on the retinal pigment epithelium (RPE). METHODS. Rhesus monkeys (age range, 7–17 years; n 18) were fed xanthophyll-free semipurified diets from birth. The diets had either low or adequate amounts of n–3 fatty acids. Six monkeys remained xanthophyll-free until death. Six received supplements of pure lutein and six of pure zeaxanthin for 6 to 24 months. The central retina was serially sectioned, and the number of RPE cells were counted in an 8-m strip along the vertical meridian. Cell counts were compared with data from control monkeys (n 15) fed a standard laboratory diet. RESULTS. Foveal and parafoveal RPE cell densities increased with age. Xanthophyll-free monkeys had a dip in the RPE cell density profile at the foveal center, rather than the normal peak. After supplementation with xanthophylls, the RPE profile of animals low in n–3 fatty acids no longer had a dip at the foveal center but became asymmetric, with higher densities in the inferior retina. In animals with adequate n–3 fatty acid levels, xanthophyll supplementation did not restore the foveal peak, and resulted in an asymmetric profile with higher densities in the superior retina. CONCLUSIONS. RPE cells are sensitive to the absence of macular pigment. Supplemental xanthophylls interact with n–3 fatty acid levels to produce asymmetries in the RPE profile. Xanthophylls and n–3 fatty acids are essential for the development and/or maintenance of a normal distribution of RPE cells. (Invest Ophthalmol Vis Sci. 2004;45:3244–3256) DOI:10.1167/iovs.02-1233

Purpose The xanthophylls lutein (L) and zeaxanthin (Z) are the primary components of macular pigment (MP) and may protect the macula from age-related degeneration (AMD). In this study, L or Z was fed to rhesus monkeys reared on xanthophyll-free diets to follow the accumulation of serum carotenoids and MP over time. Methods Eighteen rhesus monkeys were fed xanthophyll-free semipurified diets from birth until 7 to 16 years. The diets of six were then supplemented with pure L and six with pure Z at 3.9 micromol/kg per day (2.2 mg/kg per day) for 24 to 56 weeks. At baseline and 4- to 12-week intervals during supplementation, serum carotenoids were measured by HPLC, and MP density was estimated by two-wavelength reflectometry. Serum carotenoids and MP were also measured in monkeys fed a stock diet. Results Monkeys fed xanthophyll-free diets had no L or Z in serum and no detectable MP. During supplementation, serum L or Z increased rapidly over the first 4 weeks and from 16 weeks onward maintained similar levels, both several times higher than in stock-diet-fed monkeys. The central peak of MP optical density increased to a relatively steady level by 24 to 32 weeks in both L- and Z-fed groups. Rhesus monkeys fed a stock diet had lower blood concentrations of L than those found in humans and other nonhuman primates. Conclusions Rhesus monkeys respond to either dietary L or Z supplementation with increases in serum xanthophylls and MP, even after life-long xanthophyll deficiency. These animals provide a potential model to study mechanisms of protection from AMD.

Purpose To develop a standardized protocol for measuring macular pigment optical density (MPOD) of experimentally naive subjects by heterochromatic flicker photometry (HFP). Methods MPOD in eyes of 54 women, age 50 and 79 years (mean, 66), was studied. The spatial profile of MPOD was measured in the right eye, and two spatial points were also measured in the left eye. Forty-eight of these inexperienced subjects completed the protocol on two separate visits. For a subset of the group, the MPOD at two different wavelengths was measured. Results The test-retest correlation at 0.5 degrees eccentricity in the right eye was 0.9. On the second visit, more than 90% of the subjects were able to perform the HFP test with results that were consistent with the absorption spectrum of macular pigment. On the first visit, data from the inexperienced subjects deviated more from the expected relationships between the two wavelengths, presumably because they had less skill in performing the task. However, subjects with high or low macular pigment density were distinguished clearly. Conclusions Reliable and meaningful measurements of macular pigment density in older subjects can be made using HFP, with a standardized protocol in the limited time available in large epidemiologic studies. This protocol will be made freely available to other researchers on request.