PubMed Health⌕ Search

Biomedical subjects

D M Snodderly

Publications and source records attributed to D M Snodderly.

At least 37 records · Page 2Linked to original sources

Radial distribution of tocopherols in rhesus monkey retina and retinal pigment epithelium-choroid.

PURPOSE: To map vitamin E as a function of distance from the foveal center in the primate retina and retinal pigment epithelium (RPE)-choroid. METHODS: Eyecups from rhesus monkeys were dissected with circular trephines so that the innermost disc, centered on the fovea, was in the center of a series of concentric rings. Two different types of dissection were performed. For one type, the authors used circular trephines with diameters of 1, 4, 8, and 10 mm (1,4-D), whereas for the other type the diameters were 2, 5, 8, and sometimes 10 mm (2,5-D). When possible, the neural retina was separated from the RPE-choroid. Tissues were analyzed for vitamin E, retinyl palmitate, and protein. RESULTS: Surface area, volume, and protein were used as indexes of the amount of tissue analyzed. Distributions of vitamin E in neural retina were dependent on the tissue metric used and type of dissection performed. However, regardless of the tissue metric used, the central 1-mm disc of the 1,4-D was, on average, higher in vitamin E content than was the central 2-mm disc of the 2,5-D. This was particularly true when volume was the tissue metric. From the average values of vitamin E in a series of concentric discs, a composite plot of the vitamin E concentration in the neural retina was generated that took into consideration both types of dissection. That plot displayed a local maximum in the fovea and then precipitously declined to a minimum in the region between 0.5 and 1.0 mm eccentricity (near the foveal crest); at greater eccentricities, the vitamin E concentration rose to a value similar to that in the fovea, i.e., the composite plot indicated that vitamin E has a V-shaped distribution in the central neural retina. Vitamin E distribution in the RPE-choroid, with surface area as the tissue metric, also was measured. For this tissue, the foveal region displayed a local maximum. CONCLUSIONS: By combining the results of two different types of dissection, the authors found that in the neural retina, vitamin E displayed a minimum near the foveal crest. This minimum correlated anatomically with the site at which areolar (geographic) atrophy frequently occurs in retinal pigment epithelial cells in the human disease, age-related macular degeneration.

Animals↗

Comparison of fluorescein angiography with microvascular anatomy of macaque retinas.

Recent anatomic work has shown that the capillary network of the fovea is multilaminar. We have identified the elements of this network that are visualized by fluorescein angiography and those that are missed. Fluorescein angiograms of monkey retinas (Macaca fascicularis) with good visualization of individual capillaries were obtained by standard clinical techniques. Retinal whole mounts were prepared from the same animals. Anatomic drawings made from the whole mounts were used to identify which parts of the capillary network were visualized angiographically. Angiographic estimates of dimensions of the foveal avascular zone corresponded closely to the anatomy. Capillary visibility declined rapidly from near perfect visualization at the edge of the foveal avascular zone to less than 40% by 900 microns eccentricity. While all the widest capillary segments (diameter 6.1-7.0 microns) were visualized, only 43% of the modal group of capillary segments (diameter 4.1-4.5 microns) were detected. When a relatively homogeneous population of capillaries was analyzed (diameters limited to the narrow range of 4.0-5.0 microns), visualization declined monotonically with depth in the retina. Capillary segments in the nerve fiber plane were visualized more than four times as effectively as segments of comparable diameter in the deepest vascular plane. High quality angiograms accurately delineate the foveal avascular zone, but they visualize only a fraction of the adjacent multilaminar network. Therefore, current techniques may not detect the earliest nonperfusion of capillaries in vaso-occlusive diseases. Capillary visibility is a joint function of diameter and of retinal depth. The decline in visualization with retinal depth implies that light scattering in the retina degrades the angiographic image.

Animals↗

Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins.

Epidemiologic data indicate that individuals with low plasma concentrations of carotenoids and antioxidant vitamins and those who smoke cigarettes are at increased risk for age-related macular degeneration (AMD). Laboratory data show that carotenoids and antioxidant vitamins help to protect the retina from oxidative damage initiated in part by absorption of light. Primate retinas accumulate two carotenoids, lutein and zeaxanthin, as the macular pigment, which is most dense at the center of the fovea and declines rapidly in more peripheral regions. The retina also distributes alpha-tocopherol (vitamin E) in a nonuniform spatial pattern. The region of monkey retinas where carotenoids and vitamin E are both low corresponds with a locus where early signs of AMD often appear in humans. The combination of evidence suggests that carotenoids and antioxidant vitamins may help to retard some of the destructive processes in the retina and the retinal pigment epithelium that lead to age-related degeneration of the macula.

Aging↗

Organization of striate cortex of alert, trained monkeys (Macaca fascicularis): ongoing activity, stimulus selectivity, and widths of receptive field activating regions.

1. In alert macaque monkeys, multiunit activity is encountered in an alternating sequence of silent and spontaneously active zones as an electrode is lowered through the striate cortex (V1). 2. Individual neurons that are spontaneously active in the dark usually have a maintained discharge in the light. Because both types of discharge occur in the absence of deliberate stimulation, we call them the "ongoing" activity. The zones with ongoing activity correspond to the cytochrome oxidase (CytOx)-rich geniculorecipient layers 4A, 4C, and 6, whereas the adjacent layers 2/3, 4B, and 5 have little ongoing activity. 3. The widths of receptive field activating regions (ARs) are positively correlated with the cells' ongoing activity. Cells with larger ARs are preferentially located in the CytOx-rich (input) layers, and many are unselective for stimulus orientation. However, approximately 90% of the cells in the silent layers are orientation selective, and they often have small ARs. 4. The laminar distribution of selectivity for orientation and direction of movement in alert animals is consistent with earlier results from anesthetized animals, but the laminar distribution of AR widths differs. In alert macaques, the ARs of direction-selective cells in layer 4B and of orientation-selective cells in layer 5 are among the smallest in V1. 5. Our findings indicate that the input layers of V1 (4A, 4C, and 6) have a diversity of AR widths, including large ones. Cortical processing produces receptive fields in some of the output layers (4B and 5) that are restricted to small ARs with high resolution of spatial position. These results imply potent lateral and/or interlaminar interactions in alert animals in early cortical processing. The diversity of AR widths generated in V1 may contribute to detection of fine detail in the presence of contrasting backgrounds--the early stages of figure-ground discrimination.

Animals↗

Neural-vascular relationships in central retina of macaque monkeys (Macaca fascicularis).

The relationship of the vasculature to the neuronal layers was studied in whole-mounts and in sections of macaque retinas. Like other central nervous structures, primate retinas have local variations in vascularity that reflect local variations in metabolism, rather than simply tissue thickness or volume. A special feature of the retina is a dense vascular plexus in the nerve fiber layer, which is unmyelinated and hence must generate a substantial metabolic demand for ion pumping. Much of the retinal vasculature is laminated and located at specific layer boundaries. Throughout the central retina, two planes of capillaries bracket the inner nuclear layer to form a sclerad capillary network. In some regions, especially near the fovea, a second, more vitread network brackets the ganglion cell layer with another pair of capillary planes. Wherever the nerve fiber layer is thick, the vitread network becomes less planar and is multilayered. When surrounded by nerve fibers, capillaries tend to orient parallel to the fibers; when adjacent to ganglion cell bodies, the capillaries are less systematically oriented. At the border between the nerve fiber layer and the ganglion cell layer, rows of ganglion cells often interdigitate with nerve fiber bundles, resulting in local perturbations of capillary orientation. The volume of the sclerad capillary network is relatively constant at different locations, but the volume of the vitread network increases dramatically where the nerve fiber layer is thick. As a result, the vascularity of the retina is greatest in the peripapillary region near the optic disk, even though the total thickness of the peripapillary retina is comparable to the retinal thickness near the foveal crest. As many as 60-70% of the photons passing through the retina in the peripapillary region will encounter one or more capillaries before reaching a photoreceptor. Median capillary diameter increases with retinal depth from 4.5-4.7 microns in the nerve fiber layer to 5.0 microns at the sclerad border of the inner nuclear layer. Capillary diameter in the nerve fiber layer also increases near the optic disk.

Animals↗

Biological control of primate macular pigment. Biochemical and densitometric studies.

The amounts of zeaxanthin (Z) and lutein (L), the carotenoids constituting the primate macular pigment, were measured in the central retinas of monkeys (Saimiri sciureus and Macaca fascicularis). Two independent methods--reverse-phase high-performance liquid chromatography (HPLC) and microdensitometry--were used for analysis of the same set of retinas. Most of the measurements were made on retinas that had been fixed by glutaraldehyde-paraformaldehyde perfusion of the animal. Control experiments showed that this fixation did not interfere with the quantitative extraction and analysis of the carotenoids. The amount of macular pigment calculated from microdensitometry of the foveal region was proportional to the amount of pigment assayed by HPLC of the same retinal area, demonstrating that either method can be used reliably to rank the carotenoid content of aldehyde-fixed foveas. The optical density of pigment in the axial direction through the retina was higher than would be predicted if the pigment were randomly oriented. This is consistent with the idea that the nonrandom orientation of the dichroic macular pigment molecules found in previous studies contributes to increased optical filtering of the retinal image. Comparisons of the amounts of Z and L between the left and right eyes of the same monkey, within 1 mm of the foveal center, always showed excellent agreement (averaging a 5% difference for Z and 11% difference for L), whereas differences among individual monkeys were very large (up to fourfold for Z). These results indicate that the uptake and assimilation of the macular carotenoids are biologically regulated by selective mechanisms in primate retinas.

Animals↗

Distribution of individual macular pigment carotenoids in central retina of macaque and squirrel monkeys.

The spatial distribution of lutein (L) and zeaxanthin (Z), the structural isomers composing the macular pigment, was studied in the retinas of macaque monkeys (Macaca fascicularis) and squirrel monkeys (Saimiri sciureus). Spatial profiles of macular pigment optical density were obtained from retinal whole mounts. Then concentric annuli were microdissected from the fovea and adjacent regions of the same retinas. Each retinal segment was analyzed for carotenoids by high-performance liquid chromatography. Both L and Z reached their highest concentrations at the center of the fovea and declined monotonically with eccentricity for both primate species. This is inconsistent with a preferential association of L with rods. Macaque monkeys have a consistent pattern of more Z than L at the foveal center, like humans. Z declines more rapidly than L with eccentricity, so that L becomes dominant in the periphery. Squirrel monkeys (all male) showed striking individual differences. Some had more Z than L at the foveal center like macaques, but four of six had the reverse pattern, with more L than Z throughout the central retina. Individual differences among squirrel monkeys may be linked to their color vision polymorphisms. This suggests that a particular Z/L ratio in primate retinas may be associated with a specific cone phenotype, just as particular carotenoids are associated with specific cone types in vertebrates with cone oil droplets.

Animals↗

Retinal vasculature of the fovea of the squirrel monkey, Saimiri sciureus: three-dimensional architecture, visual screening, and relationships to the neuronal layers.

The retinal vasculature of the fovea of squirrel monkeys was studied in retinal whole mounts and in sections of the same retinas. At the center of the fovea there is an approximately circular avascular zone surrounded by a set of terminal capillaries in the inner nuclear layer. Within the foveal depression, four capillary planes that bear a precise relationship to the neuronal organization appear in a specific sequence with increasing eccentricity. The first plane to be established is the dominant, most voluminous one, located closest to the photoreceptors at the deep (sclerad) border of the inner nuclear layer. A second major plane appears next at the sclerad border of the ganglion cell layer. The two remaining, less voluminous planes occur at a slightly greater eccentricity. One of these, located at the shallow (vitread) border of the inner nuclear layer, often drains into the ganglion cell plane. The fourth plane is initially situated at the vitread border of the ganglion cell layer; with increasing eccentricity it moves into the nerve fiber layer. These capillaries are oriented like the nerve fibers with which they travel. Both the shallow inner nuclear and nerve fiber planes of capillaries show marked regional variations. The capillary planes are within or adjacent to regions of high cytochrome oxidase activity. The retinal vascular network is an unrecognized contributor to the optical filtering properties of the eye. In much of the central retina, a photon has a 40-50% chance of encountering one or more capillaries before it reaches a photoreceptor.

Animals↗

Structural and geometrical isomers of carotenoids in human plasma.

We have quantitatively analyzed human plasma for the following carotenoids: all-trans-lutein, all-trans-zeaxanthin, alpha-cryptoxanthin, beta-cryptoxanthin, the sum of all-trans-lycopene and its cis isomers, alpha-carotene and beta-carotene. In addition, we have tentatively identified and quantified 13-cis-lutein and 13-cis-zeaxanthin in human plasma. The latter two cis isomers are also apparent in samples of two common food items, spinach and corn meal. We have analyzed the ratios of all of the members of the beta, beta family of carotenoids (zeaxanthin, beta-cryptoxanthin and beta-carotene) to their corresponding beta, epsilon structural isomers (lutein, alpha-cryptoxanthin and alpha-carotene) in human plasma. There are marked differences in these ratios, with beta-carotene and beta-cryptoxanthin predominating in the carotene and monohydroxy-xanthophyll classes and lutein predominating in the dihydroxy-xanthophyll class. These differences could be attributable to dietary intake or to specific mechanisms in the way humans absorb and utilize these compounds.

Adult↗

Plasma carotenoids of monkeys (Macaca fascicularis and Saimiri sciureus) fed a nonpurified diet.

The major carotenoid pigments in the plasma and in a common, nonpurified diet of two species of monkeys (Macaca fascicularis and Saimiri sciureus) were measured. The xanthophylls, lutein, zeaxanthin, alpha-cryptoxanthin, and beta-cryptoxanthin, were the principal carotenoids in both the diet and the plasma. Lutein and zeaxanthin were abundant in the all-trans, the 9-cis, and the 13-cis geometrical isomers in the diet, but the 9-cis form was rarely measurable in plasma. However, the 13-cis isomers of lutein and zeaxanthin were found in higher proportions in plasma than in the diet. For both the monohydroxy-xanthophylls, alpha-cryptoxanthin and beta-cryptoxanthin, and the dihydroxy-xanthophylls, lutein and zeaxanthin, the beta, beta structural isomer (beta-cryptoxanthin or zeaxanthin) is less abundant than the beta, epsilon isomer in plasma than in the diet. These results indicate substantial specificity in the absorption or retention of closely related carotenoid isomers in primates. The proportions of different geometrical isomers of lutein and zeaxanthin in the plasma of both species of monkeys were nearly identical and were similar to human values. The hydrocarbon carotenoids, alpha-carotene, beta-carotene and lycopene were usually undetectable in monkey plasma. The monkeys appear to be like humans in their utilization of lutein and zeaxanthin but distinctly different in some other aspects of carotenoid utilization.

Animal Feed↗

Effects of light and dark environments on macaque and human fixational eye movements.

Eye position of two macaques and two humans was recorded while they detected the unpredictable dimming of a fixation spot in a dark or a light environment. Fixational saccades often had complex waveforms that resulted from clustering of two or more saccadic displacements with no intervening drift periods. In the dark, all subjects had low frequencies of saccade clusters (0.15-0.61/sec). Three of the subjects increased the frequency of saccade clusters and decreased the magnitude of the displacements when the task was performed in the normally lighted laboratory. The higher saccade frequencies in the light did not automatically result in greater dispersion of eye position. One of the humans, who had the lowest saccade frequency, was relatively unaffected by the stimulus conditions. The change in stimulus conditions had a more pronounced effect on the fixational eye movements of the macaques than the humans. In the dark, the macaques made saccades mostly down and nasal, but in the light the saccadic displacements occurred over a wider range of angular directions. Mean eye position was higher in the dark than in the light. The humans altered the direction of their saccadic displacements very little and did not change their mean eye position when they switched from a dark to a lighted environment. The influence of a lighted environment is interpreted as an interaction between foveolar and peripheral retinal inputs. The results suggest that fixational saccades may have more than one role, perhaps including stimulation of pathways originating in the peripheral retina. These peripheral field inputs have a stronger effect on the fixational control system of macaques than of humans.

Adult↗

Studying striate cortex neurons in behaving monkeys: benefits of image stabilization.

Responses of single cells in the striate cortex of a behaving monkey were studied while the eye movements of fixation were monitored with high precision. Receptive fields of cortical neurons moved in space with the eye. When the eye position signal was used to stabilize the image on the retina, response rates were more vigorous and more reliable. When the image was not stabilized, the estimates of receptive field activating areas were influenced (usually inflated) in unpredictable ways. With stabilization, small receptive fields can be studied and powerful surround interactions become apparent.

Action Potentials↗

Eye position during fixation tasks: comparison of macaque and human.

Two macaques and three humans fixated luminous targets in a dark field. All subjects had greater dispersion of eye position from trial-to-trial (between-trial variability) than would be predicted from sampling error and within-trial variability. Monkeys had greater between-trial dispersion on the vertical meridian than humans because of less precise control of saccades. Mean vertical eye position of the monkeys varied idiosyncratically with the fixation task (spot-dim or line-tilt). Between-trial fixation variability of both monkeys and humans was large enough to affect the interpretation of experiments relating visual performance to retinal anatomy or to neurophysiology.

Adult↗

The macular pigment. I. Absorbance spectra, localization, and discrimination from other yellow pigments in primate retinas.

The nonbleaching yellow pigments of the primate fovea were studied by microspectrophotometry (MSP). Retinas fixed with glutaraldehyde/paraformaldehyde mixtures retained yellow pigments with absorbance spectra very similar to those recorded by MSP in fresh retinas. This allowed the authors to prepare retinal sections for localization of the pigments. The spectrum of the macular pigment in fixed tissue is shifted slightly (about 6 nm) toward longer wavelengths, with maximum absorbance at 460 nm. Two short-wavelength yellow pigments also have been identified, with absorbance maxima at 410 nm ( P410 ) and 435 nm ( P435 ), respectively. All three yellow pigments are present in the fovea. The short-wavelength pigments are detected more easily outside the central foveal region because the macular pigment does not obscure them there. They are especially apparent when the MSP beam is confined to the outer nuclear layer or the inner segment layer of retinal sections. The macular pigment is most dense in the fiber layers (receptor axon layer and inner plexiform layer); its density declines markedly with retinal eccentricity. The maximal absorbance of P410 and P435 is usually lower than that of the macular pigment in the central fovea, but their densities and relative proportions change more gradually with eccentricity. Consequently, their maximal absorbance is higher than that of the macular pigment outside the foveal center. The P410 and P435 pigments may be two different oxidation states of one or more respiratory hemoproteins. Commonly used procedures for estimating the absorbance spectrum of the macular pigment by comparing the foveal center with a parafoveal region may be influenced by the amounts and the oxidation states of the short-wavelength pigments in the living eye.

Animals↗

The macular pigment. II. Spatial distribution in primate retinas.

The spatial density distribution of macular pigment in primate retinas was described by two-wavelength microdensitometry of retinal sections. The macular pigment is most dense along the path of the receptor axons in the center of the fovea. Another band of high density is present in the inner plexiform layer in many retinas. The density in both fiber layers declines to low, relatively constant levels within 1 mm eccentricity. Both the total retinal density of macular pigment and the contributions of subsets of the retinal layers were estimated by integrating along the path of light traversing the retina from the vitreal surface to the outer segments. The integrated densities were measured at several eccentricities to establish the profile of macular pigment density along a diameter through the fovea. The macular pigment profile was unimodal in some cases and trimodal in others. The main central peak always occurred in the center of the fovea. The total retinal density of the central peak ranged from 0.42-1.0 absorbance. Most of the pigment is interposed between the outer segments and the stimulating light and is effective as a visual filter. The macular pigment is dichroic, with the major axis of absorption oriented tangential to a circle centered on the fovea. This is consistent with commonly accepted explanations of Haidinger 's brushes.

Animals↗

Intensity coding in primate visual system.

The pupil reflex and the discharge of LGN cells of the awake macaque were measured under stimulus conditions that yielded evidence for wide-range intensity coding in human psychophysical experiments. Ganzfeld flashes of white light were delivered under dark-adapted conditions to the surgically immobilized eye of the monkey while the other eye was observed in the infrared. Three-sec flashes elicited a consensual pupil reflex that was graded from -8 to 0 log Lamberts (L), indicating that the optic nerve fibers are capable of coding at least an 8 log-unit range of light intensity. In the physiological experiments, shorter flashes (0.1-0.5 sec) but otherwise identical conditions elicited monotonically graded responses from one type of LGN cell over the photopic range of -5 to 0 log L. Responses from other types of LGN cells were also graded over wide ranges but had different thresholds and, in some cases, nonmonotonic intensity-response functions. Latency of the excitatory LGN responses decreased with increasing intensity according to a power function with slope of-0.08. The pupil reflex and the LGN cell excitatory responses approximate power functions of light intensity with exponents of 0.22 and 0.14-0.29 respectively. The range of intensity coding found for single LGN cells is the widest yet reported for diffuse stimuli.

Animals↗

Evaluation of a surgical method for immobilizing the eye of an alert monkey.

One eye of a macaque monkey was immobilized by severing the third, fourth, and sixth cranial nerves. The residual movements of the operated eye were measured by repeatedly mapping the position of a visual receptive field. Movements of several degrees were caused by contraction of the orbital musculature during the closure blink. The amount of movement was dramatically reduced by paralysis of the superficial orbital muscles with a local anesthetic. Side effects of surgical immobilization include increased risk of corneal clouding and eye infection. In one monkey intraocular pressure was lowered for several weeks. Regeneration of the severed nerves causes return of some voluntary movement of the eye, which is not coordinated with movements of the unoperated eye even after nine months postoperative survival. The suitability of this approach for studies on the visual nervous system is discussed.

Abducens Nerve↗