Biomedical subjects

D M Snodderly

Publications and source records attributed to D M Snodderly.

At least 19 recordsLinked to original sources

PubMed2001

Macular pigment density measured by autofluorescence spectrometry: comparison with reflectometry and heterochromatic flicker photometry.

We present a technique for estimating the density of the human macular pigment noninvasively that takes advantage of the autofluorescence of lipofuscin, which is normally present in the human retinal pigment epithelium. By measuring the intensity of fluorescence at 710 nm, where macular pigment has essentially zero absorption, and stimulating the fluorescence with two wavelengths, one well absorbed by macular pigment and the other minimally absorbed by macular pigment, we can make accurate single-pass measurements of the macular pigment density. We used the technique to measure macular pigment density in a group of 159 subjects with normal retinal status ranging in age between 15 and 80 years. Average macular pigment density was 0.48 +/- 0.16 density unit (D.U.) for a 2 degrees -diameter test field. We show that these estimates are highly correlated with reflectometric (mean: 0.23 +/- 0.07 D.U.) and psychophysical (mean: 0.37 +/- 0.26 D.U.; obtained by heterochromatic flicker photometry) estimates of macular pigment in the same subjects, despite the fact that systematic differences in the estimated density exist between techniques. Repeat measurements over both short- and long-time intervals indicate that the autofluorescence technique is reproducible: The mean absolute difference between estimates was less than 0.05 D.U., superior to the reproducibility obtained by reflectometry and flicker photometry. To understand the systematic differences between density estimates obtained from the different methods, we analyzed the underlying assumptions of each technique. Specifically, we looked at the effect of self-screening by visual pigment, the effect of changes in optical property of the deeper retinal layers, including the role of retinal pigmented epithelium melanin, and the role of secondary fluorophores and reflectors in the anterior layers of the retina.

Adult↗

PubMed2000

Relation among serum and tissue concentrations of lutein and zeaxanthin and macular pigment density.

BACKGROUND: Lutein and zeaxanthin are the only carotenoids in the macular region of the retina (referred to as macular pigment [MP]). Foods that are rich in lutein and zeaxanthin can increase MP density. Response to dietary lutein and zeaxanthin in other tissues has not been studied. OBJECTIVE: The objective of this study was to examine tissue responses to dietary lutein and zeaxanthin and relations among tissues in lutein and zeaxanthin concentrations. DESIGN: Seven subjects consumed spinach and corn, which contain lutein and zeaxanthin, with their daily diets for 15 wk. At 0, 4, 8, and 15 wk and 2 mo after the study, serum, buccal mucosa cells, and adipose tissue were analyzed for carotenoids, and MP density was measured. RESULTS: Serum and buccal cell concentrations of lutein increased significantly from baseline during dietary modification. Serum zeaxanthin concentrations were greater than at baseline only at 4 wk, whereas buccal cell and adipose tissue concentrations of zeaxanthin did not change. Adipose tissue lutein concentrations peaked at 8 wk. Changes in adipose tissue lutein concentration were inversely related to the changes in MP density, suggesting an interaction between adipose tissue and retina in lutein metabolism. To investigate the possibility of tissue interactions, we examined cross-sectional relations among serum, tissue, and dietary lutein concentrations, anthropometric measures, and MP density in healthy adults. Significant negative correlations were found between adipose tissue lutein concentrations and MP for women, but a significant positive relation was found for men. CONCLUSION: Sex differences in lutein metabolism may be an important factor in tissue interactions and in determining MP density.

Adipose Tissue↗

PubMed2000

Iris color and age-related changes in lens optical density.

PURPOSE: Epidemiologic evidence indicates that dark iris color increases risk of age-related cataract. No information is currently available, however, on the effects of iris color on the lens prior to cataract development. In this study, we relate iris color to lens optical density (OD) in individuals without frank cataract. METHODS: 90 subjects with blue or green irises (light color) were compared with 87 subjects having hazel, brown, or black irises (dark color). Lens OD was measured psychophysically by comparing scotopic thresholds obtained at 410 (measuring) and 550 nm (reference). Stimuli were presented in Maxwellian view. RESULTS: The groups with light and with dark iris color did not differ significantly in smoking habits, dietary patterns, or age. Despite other similarities between the groups, lens OD was significantly (p < 0.024) higher in the group with dark irises. The higher OD of the dark iris group was due to differences in the older subjects (> 45 years, p < 0.005), rather than the younger subjects (20-45 years) who showed no differences in lens OD. CONCLUSION: Our data indicate that iris pigmentation may be directly related to age-associated increases in lens OD.

Adult↗

PubMed1999

Physiological properties of macaque V1 neurons are correlated with extracellular spike amplitude, duration, and polarity.

In the lateral geniculate nucleus (LGN) the large neurons of the magnocellular layers are functionally distinct and anatomically segregated from the small neurons of the parvocellular layers. This segregation of large and small cells is not maintained in the primary visual cortex (V1); instead a heterogeneous mixture of cells occurs, particularly in the output layers. Nevertheless, our results indicate that for the middle and upper layers of V1, cell size remains a predictor of physiological properties. We recorded extracellularly from neurons in V1 of alert monkeys and analyzed the amplitude, duration, and polarity of the action potentials of 199 cells. Of 156 cells that could be assigned to specific cortical layers, 137 (88%) were localized to the middle and upper cortical layers, layer 4 and above. We summarize evidence that the large-amplitude spikes are discharged by large cells, whereas small-amplitude spikes are the action potentials of smaller cells. Large spikes were predominantly negative and of longer duration, whereas small spikes were predominantly positive and briefer. The putative large cells had lower ongoing activity, smaller receptive field activating regions and higher selectivity for stimulus geometry and stimulus motion than the small cells. The contrasting properties of the large and the small cells were illustrated dramatically in simultaneous recordings made from adjacent cells. Our results imply that there may be an anatomic pairing or clustering of small and large cells that could be integral to the functional organization of the cortex. We suggest that the small and the large cells of area V1 have different roles, such that the small cells may shape the properties of the large output cells. If some of the small cells are also output cells, then cell size should be a predictor of the type of information being sent to other brain regions. Because of their high activity and relative ease of stimulation, the small cells also may contribute disproportionately to in vivo images based on metabolic responses such as changes in blood flow.

Action Potentials↗

PubMed1999

A practical method for measuring macular pigment optical density.

PURPOSE: Increasing evidence indicates that the macular pigments (MP) protect the central retina and may retard macular disease. For that reason, a practical method for measuring MP that does not require elaborate optics and can be applied to diverse populations by operators with a modest amount of experience was developed and validated. METHODS: A small tabletop device based on light-emitting diodes (LEDs) as the light source with electronic controls was constructed. Macular pigment was measured with the tabletop device with a 1 degrees test stimulus at 460 nm using heterochromatic flicker photometry, and the results were compared with measurements using a traditional three-channel Maxwellian view system with a xenon-arc source. RESULTS: Macular pigment density of 30 subjects (age range, 16-60 years) was measured with both stimulus systems. Macular pigment measured with the LED tabletop device in free view was highly correlated with MP measured in Maxwellian view (y = -0.03 + 1.06x, r = +0.95). The average absolute difference between the two techniques was 0.04 (SD, 0.03). The new technique was not significantly affected by variations in lens optical density, pupil size, or small head movements. CONCLUSIONS: Psychophysical measurement of MP provides a unique opportunity to make repeated noninvasive assessment of the concentration of a protective nutrient in the retina. The availability of this new device should make this measurement technology accessible to a wide variety of investigators for application to diverse populations.

Adolescent↗

PubMed1998

Preservation of visual sensitivity of older subjects: association with macular pigment density.

PURPOSE: The authors investigated how individual differences in macular pigment (MP) density are related to loss of visual sensitivity with age. METHODS: Macular pigment and visual sensitivity of 27 healthy older subjects (aged 60-84 years) were compared with data from 10 younger subjects (aged 24-36 years). Macular pigment density was measured psychophysically with a centrally fixated stimulus 1 degree in diameter. Photopic increment sensitivity in the fovea was measured as thresholds for centrally fixated 1 degree stimuli on a bright yellow background. Foveal sensitivity of the pi-1 mechanism driven by the S cones was measured with 440-nm light. Photopic increment thresholds not determined by the pi-1 mechanism were measured with 550-nm light. Sensitivity was specified at the photoreceptor outer segments by individually correcting for psychophysically determined lens density and MP density. Dark-adapted (scotopic) sensitivity of rod-dominated visual mechanisms was measured in the parafovea with 550-nm light at 8 degrees eccentricity. RESULTS: Consistent with past reports, photopic sensitivity declined significantly with age for both 440-nm (P < 0.025) and 550-nm (P < 0.0003) light. For older subjects, photopic sensitivity was positively related to MP density, although more strongly for 440-nm (P < 0.001) than for 550-nm (P < 0.01) light. Parafoveal scotopic sensitivity of the older subjects was also positively related to MP density (P < 0.02). Visual sensitivity of the young subjects was not significantly related to MP density. CONCLUSIONS: For subjects older than 60 years, visual sensitivity of those with high MP density was not significantly different from that of young subjects. Conversely, older subjects with low MP density had lower sensitivity than young subjects. Although this study cannot prove causality, the results show that high MP density was associated with the retention of youthful visual sensitivity, which suggested that MP may retard age-related declines in visual function.

Adaptation, Ocular↗

PubMed1997

Response variability of neurons in primary visual cortex (V1) of alert monkeys.

Response variability of neurons limits the reliability and resolution of sensory systems. It is generally thought that response variability in the visual system increases at cortical levels, but the causes of the variability have not been identified. We have measured the response variability of neurons in primary visual cortex (V1) of alert monkeys. We recorded from 80 single cells distributed over all V1 layers and from 8 parvocellular cells of the lateral geniculate nucleus. All cells were stimulated with a bar of near-optimal orientation, color, and dimensions while continuously monitoring the eye movements of fixation. To minimize the effects of eye movements, responses that occurred while the eye was relatively steady were selected for analysis. The impulses elicited by each stimulus presentation were counted, and the variance and coefficient of variation were computed. Both measures of response variability were much lower than reported previously for V1 cells of both alert and anesthetized monkeys. Our data show that fixational eye movements cause a large component of response variance in alert monkeys. Moreover, the reliability of V1 neurons is not obviously degraded compared with lateral geniculate nucleus cells. The high reliability of neurons in alert monkeys is consistent with expectations from conventional biophysical models, and it suggests that activity in a modest number of neurons may suffice to form a perceptual decision.

Animals↗

PubMed1997

Retinyl palmitate in macaque retina-retinal pigment epithelium-choroid: distribution and correlation with age and vitamin E.

Retinyl palmitate (RP) and retinyl stearate (RS) are of central importance in the visual cycle because they are the major storage molecules for retinol. In some tissues (e.g. liver) the amount of vitamin A (mostly in the form of retinyl ester) is positively correlated with both the amount of alpha-tocopherol (alpha-T) and age. Furthermore, alpha-T is a noncompetitive inhibitor of the hydrolysis of RP. We measured RP, RS, alpha-T and beta+gamma-tocopherol (beta+gamma-T) as functions of distance from the foveal center (eccentricity) in the retina-RPE-choroid (NRC) of rhesus monkeys using high-pressure liquid chromatography. It was found that the central and peripheral NRC differed with respect to these parameters. The concentration (pmoles sq mm-1) of RP was higher in the central NRC than in the peripheral NRC and was at a maximum in the region of the fovea. Furthermore, although in the peripheral NRC. RP was well correlated with age and alpha-T (similar to other tissues), in the central NRC, RP per sq mm was more clearly related to photoreceptor density. These differences imply that the central NRC controls the concentration of RP within it, while the concentration of RP in the peripheral NRC is determined by its environment (e.g. nutrients available from blood) and the age of the individual.

Age Factors↗

PubMed1997

Visual receptive fields of neurons in primary visual cortex (V1) move in space with the eye movements of fixation.

We tested the hypothesis that receptive field (RF) locations of visual cortex cells maintain a fixed location on the retina and move in space with movements of the eye. Responses to a bar swept across the RF were recorded from 29 neurons in V1 (26) and V2 (3) of alert monkeys while precisely monitoring the eye movements of fixation. There was a tight correlation and a near unity ratio between eye position and RF position. This implies that RFs of V1 neurons and at least some V2 neurons are fixed to specific retinal locations, rather than being shifted on the retina by attention-controlled mechanisms. V1 neurons thus differ from those polysensory neurons whose RF locations on the retina are dynamically altered to maintain a desired position in space.

Animals↗

PubMed1997

A dissociation between brain activity and perception: chromatically opponent cortical neurons signal chromatic flicker that is not perceived.

When two isoluminant colors alternate at frequencies > 10 Hz, we perceive only one fused color with a minimal sensation of brightness flicker. In spite of the perception of color fusion, color opponent (CO) cells at early stages of the visual pathway are known to respond to chromatic flicker at frequencies far exceeding the perceptual fusion frequency. To explain color fusion, several groups have predicted that CO cells in V1-unlike the retina and lateral geniculate nucleus-should not follow high-frequency flicker. To test this prediction we recorded from 12 CO cells in various V1 layers. We found, contrary to expectations, that these neurons follow high frequency flicker well above heterochromatic fusion frequencies. All followed 15 Hz flicker and 10/12 followed 30 Hz flicker. For three cells, we tested 60 Hz luminance flicker and found clear responses. We thus present evidence of cortical activity in alert, trained monkeys that is clearly representing visual stimulation, yet is not perceived. Our data call into question explanations of perceptual phenomena that invoke a low temporal frequency cut-off of CO cells in V1 to account for the failure to perceive fast temporal changes in the chromatic domain.

Animals↗

PubMed1997

Dietary manipulation of plasma carotenoid concentrations of squirrel monkeys (Saimiri sciureus).

Primate retinas accumulate the dihydroxy xanthophylls, lutein and zeaxanthin, from the diet via the plasma. Control of plasma concentrations of these carotenoids may be useful for prevention of retinal disease by manipulating carotenoid content of the retina. We have measured the plasma response of male squirrel monkeys to changes in the carotenoid content of a nonpurified diet. We have also supplemented the diet with zeaxanthin and beta-carotene. Plasma responses to dietary changes were rapid. Within one week, most of the change in plasma concentrations had already occurred. Within two weeks of increasing zeaxanthin intake, plasma zeaxanthin concentrations were at a new, relatively stable level. beta-carotene concentrations in the plasma were low while the monkeys were consuming a standard laboratory diet, and were only slightly increased by supplementation. Plasma lutein concentrations were unaffected by zeaxanthin supplementation. Our results suggest that it should be possible to manipulate plasma concentrations of each of the retinal carotenoids with little impact on the plasma concentrations of the other. This will facilitate exploration of the rates of accumulation of lutein and zeaxanthin in the retina, as well as exploration of the possibility of bioconversion from one xanthophyll to another.

Animals↗

PubMed1997

Density of the human crystalline lens is related to the macular pigment carotenoids, lutein and zeaxanthin.

PURPOSE: Although oxidative stress may play an important role in the development of age-related cataract, the degree of protection reported for antioxidant vitamins and carotenoids has been inconsistent across studies. These varied results may be due in part to the lack of good biomarkers for measuring the long-term nutritional status of the eye. The present experiments investigated the relationship between retinal carotenoids (i.e., macular pigment), used as a long-term measure of tissue carotenoids, and lens optical density, used as an indicator of lens health. METHODS: Macular pigment (460 nm) and lens (440, 500, and 550 nm) optical density were measured psychophysically in the same individuals. Groups of younger subjects--7 females (ages 24 to 36 years), and 5 males (ages 24 to 31 years)--were compared with older subjects--23 older females (ages 55 to 78 years), and 16 older males (ages 48 to 82 years). RESULTS: Lens density (440 nm) increased as a function of age (r = 0.65, p < 0.001), as expected. For the oldest group, a significant inverse relationship (y = 1.53-0.83x, r = -0.47, p < 0.001) was found between macular pigment density (440 nm) and lens density (440 nm). No relationship was found for the youngest group (p < 0.42). CONCLUSIONS: The main finding of this study was an age-dependent, inverse relationship between macular pigment density and lens density. Macular pigment is composed of lutein and zeaxanthin, the only two carotenoids that have been identified in the human lens. Thus, an inverse relationship between these two variables suggests that lutein and zeaxanthin, or other dietary factors with which they are correlated, may retard age-related increases in lens density.

Adult↗

PubMed1997

Individual variations in the spatial profile of human macular pigment.

Individual variations in the spatial profile of macular pigment (MP) density were measured for 32 subjects. Peak density of MP measured with a 460-nm, 12-arcmin stimulus averaged 0.58, standard deviation (SD) = 0.26, with a range of 0.175 to 1.39. To assess the symmetry of the MP distribution, MP density was measured on the horizontal and vertical meridians at +/-1 deg eccentricity. The density varied by no more than 16% at these four locations, indicating a basically symmetric distribution. Based on a linear interpolation between measured locations, the width of the spatial distribution of MP at half the maximal density averaged 1.03 deg, SD = 0.38, with a range of 0.25 to 1.9 deg. The average spatial profile of MP density across subjects was fitted with both an exponential and a Gaussian function. An exponential decay with eccentricity explained more variance in the data than did a Gaussian function. Assuming an exponential decay with eccentricity, once MP density has been measured in the center of the retina (denoted A), MP density at more eccentric locations (X, deg) can be predicted with a standardized equation (MP = A x 10(-0.42x)). For individual cases, small deviations from an exponential function suggest the existence of minor flanking peaks or shoulders for 40% of the subjects. We also examined the temporal stability of the MP profile of four subjects over a time span of 4-14 months and for a single spatial location for ten subjects over a time span of 1-16 years. These longitudinal data show that differences in MP density among subjects are maintained over time, if dietary patterns are stable.

Adult↗

PubMed1997

Dietary modification of human macular pigment density.

PURPOSE: The retinal carotenoids lutein (L) and zeaxanthin (Z) that form the macular pigment (MP) may help to prevent neovascular age-related macular degeneration. The purpose of this study was to determine whether MP density in the retina could be raised by increasing dietary intake of L and Z from foods. METHODS: Macular pigment was measured psychophysically for 13 subjects. Serum concentrations of L, Z, and beta-carotene were measured by high-performance liquid chromatography. Eleven subjects modified their usual daily diets by adding 60 g of spinach (10.8 mg L, 0.3 mg Z, 5 mg beta-carotene) and ten also added 150 g of corn (0.3 mg Z, 0.4 mg L); two other subjects were given only corn. Dietary modification lasted up to 15 weeks. RESULTS: For the subjects fed spinach or spinach and corn, three types of responses to dietary modification were identified: Eight "retinal responders" had increases in serum L (mean, 33%; SD, 22%) and in MP density (mean, 19%; SD, 11%); two "retinal nonresponders" showed substantial increases in serum L (mean, 31%) but not in MP density (mean, -11%); one "serum and retinal nonresponder" showed no changes in serum L, Z, or beta-carotene and no change in MP density. For the two subjects given only corn, serum L changed little (+11%, -6%), but in one subject serum Z increased (70%) and MP density increased (25%). CONCLUSIONS: Increases in MP density were obtained within 4 weeks of dietary modification for most, but not all, subjects. When MP density increased with dietary modification, it remained elevated for at least several months after resuming an unmodified diet. Augmentation of MP for both experimental and clinical investigation appears to be feasible for many persons.

Adult↗

PubMed1996

Iris color and macular pigment optical density.

The present study was designed to assess the relationship between iris color and macular pigment optical density. Both melanin and carotenoids (responsible for iris color and macular pigment composition, respectively) appear to protect the retina through similar mechanisms and higher concentrations may reduce the incidence of retinal degenerations. To evaluate this relationship, 95 subjects were examined and the following variables were measured: iris color; macular pigment optical density (MP); plasma concentrations of lutein and zeaxanthin and beta-carotene; dietary intake of lutein and zeaxanthin and beta-carotene; and total fat intake. Iris color was determined by self assessment and classified as blue or gray (group I), green or hazel (group II) or brown or black (group III). MP density was measured psychophysically by measuring foveal and parafoveal sensitivities to lights of 460 and 550 nm, using the method of heterochromatic flicker photometry. Plasma carotenoid concentrations were measured using reverse-phase high-performance liquid chromatography. Dietary intake was determined by a detailed food-frequency questionnaire. Despite similarities in diet and in blood concentrations of carotenoids, significant differences in macular pigment density (P < 0.02) were found for different colored irises (group I, n = 38, MP = 0.25; group II, n = 26, MP = 0.32; group III, n = 31, MP = 0.38). The covariation of iris color and MP indicates that past epidemiologic studies have not adequately determined the independent effects of either factor. The relationship of MP and iris color may be the result of one or two factors: the evolution of a shared tendency to accumulate melanin and carotenoids due to similar environmental pressures (e.g. light and oxygen); and/or MP might be depleted due to the tendency for eyes with light irises to transmit more light than eyes with dark irises, thus causing increased oxidative stress.

Adult↗

PubMed1996

Sex differences in macular pigment optical density: relation to plasma carotenoid concentrations and dietary patterns.

Sex differences in macular pigment (MP) optical density (measured psychophysically) were examined. Concentrations of lutein and zeaxanthin (L and Z) (non-separated) and beta-carotene (BC) in the blood were determined using reverse phase high-performance liquid chromatography. Dietary intake of L and Z, BC, fat, and iron were estimated by questionnaire. Males had 38% higher MP density than females (P < 0.001) despite similar plasma carotenoid concentrations and similar dietary intake (except for fat). Dietary intake of carotenoids, fat and iron, as well as plasma concentrations of L and Z were positively related to MP density in males. Conversely, only plasma L and Z was related to MP density for females, and dietary fat was negatively related to MP density. Sex differences in protection of the retina by MP and in the relationship between the retina, blood and diet could be a factor in the incidence of retinal diseases, especially age-related macular degeneration.

Adult↗

PubMed1996

Cigarette smoking and retinal carotenoids: implications for age-related macular degeneration.

The foveal region of the retina has a yellow pigmentation composed primarily of the carotenoids lutein and zeaxanthin. Past studies have shown that cigarette smoking depresses carotenoid concentrations in the blood. This is the first report on the effects of cigarette smoking on carotenoids in the retina. Macular pigment optical density (MP) was measured psychophysically by comparing foveal and parafoveal sensitivities to light of 460 and 550 nm. General dietary patterns, smoking frequency (cigaretts/day) and personal data were collected by questionnaire. Thirty-four smokers and 34 nonsmokers were compared. Subjects were matched with respect to age, sex, dietary patterns and overall pigmentation (i.e., eye, skin and hair color). The smoking group had a mean MP of 0.16 (SD = 0.12) compared to a mean MP of 0.34 (SD = 0.15) for nonsmokers (P < 0.0001). MP density and smoking frequency were inversely related (r = -0.498 P < 0.001) in a dose-response relationship. A variety of evidence suggests that MP protects the macula from actinic damage both passively (by screening potentially harmful short-wave light) and actively as an antioxidant (e.g., by quenching reactive oxygen species). If smoking causes a reduction in MP density, then smokers may be at risk. Epidemiologic data identifying smoking as a risk factor for the neovascular form of age-related macular degeneration are consistent with this hypothesis.

Adult↗

PubMed1996

Vitamin E, retinyl palmitate, and protein in rhesus monkey retina and retinal pigment epithelium-choroid.

PURPOSE: To measure the amounts of vitamin E, retinyl palmitate, and protein in the primate retina and its supporting tissues-the retinal pigment epithelium and choroid. To compare the amounts and concentrations of these materials in the central retina with those in the peripheral retina and to compare the concentration of vitamin E in the retina with that in plasma. Finally, to compare these results in rhesus monkey with existing measurements in humans. METHODS: Ocular tissues from rhesus monkeys (Macaca mulatta) were extracted with a two-phase solvent system. Components in the extract were separated by reverse-phase high-pressure liquid chromatography. Two detectors in series monitored the effluent: Vitamin E was quantified with an internal standard and fluorescence detection, whereas retinyl palmitate was quantified with an external standard and ultraviolet light detection. RESULTS: Amounts of vitamin E, retinyl palmitate, and protein in tissues from rhesus monkey compared reasonably well with those reported for humans. The content of vitamin E in the peripheral neural retina was moderately correlated with its protein content and, to a greater extent, with the concentration of vitamin E in the plasma; however, the content of vitamin E in the central neural retina correlated only with the amount of protein in the central neural retina. CONCLUSIONS: These results are consistent with rhesus monkey as a model for the use of vitamin E by human ocular tissues. The amount of vitamin E in the central neural retina appears to be more closely regulated than the amount of vitamin E in the peripheral neural retina.

Animals↗