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Biomedical subjects

K R Sloan

Publications and source records attributed to K R Sloan.

7 recordsLinked to original sources

Packing geometry of human cone photoreceptors: variation with eccentricity and evidence for local anisotropy.

Disorder in the packing geometry of the human cone mosaic is believed to help alleviate spatial aliasing effects. To characterize cone packing geometry, we gathered positions of cone inner segments at seven locations along four primary and two oblique meridians in an adult human retina. We generated statistical descriptors based on the distribution of distances and angles to Voronoi neighbors. Parameters of a compressed-jittered model were fit to the actual mosaic. Local anisotropies were investigated using correlograms. We find that (1) median distance between Voronoi neighbors increases with eccentricity, but the minimum distance is constant (6-8 microns) across peripheral retina; (2) the cone mosaic is least compressed and jittered at the edge of the foveal rod-free zone; (3) disorder in the foveal center resembles that described by Pum et al. (1990); (4) cone spacing is 10-15% less in one direction than in the orthogonal direction; and (5) cone spacing is greater in the radial direction (along meridians) than in the tangential direction (along lines of isoeccentricity). The nearly constant minimum distance implies that high spatial frequencies may be sampled even in peripheral retina. Local anisotropy of the cone mosaic is discussed in relation to the growth of the primate retina during development and to the orientation biases of retinal ganglion cells.

Adult

Distribution and morphology of human cone photoreceptors stained with anti-blue opsin.

Primate cones maximally sensitive to short wavelength light (blue cones) have been previously identified by using indirect methods. We stained 7 wholemounted human retinas obtained from 6 female donors, using an affinity purified antibody to a 19 amino acid peptide sequence at the N-terminus of blue opsin (Lerea et al., '89: Neuron 3:367-376), standard PAP immunocytochemistry, and controls. Cones were counted where all outer segments could be traced to inner segments and were measured where cells were well aligned vertically. We find that: (1) 7% of cones within 4 mm of the foveal center are labeled by antiblue opsin; (2) compared to neighboring red/green cones, blue cone inner segments are 10% taller, have a larger cross-sectional diameter near the junction with the outer segment, and a smaller diameter near the external limiting membrane, resulting in a more cylindrical shape, (3) foveal blue cones are sparse, irregularly spaced, and missing in a zone about 100 microns (0.35 degrees) in diameter near the site of peak cone density, (4) the highest densities of blue cones (greater than 2,000 cells/mm2) are found in a ring at 0.1-0.3 mm eccentricity, and (5) the shortest distances between neighboring cones are between blue and red/green cones, and the blue and red/green mosaics are statistically independent. These findings are consistent with psychophysical reports of foveal tritanopia and maximum sensitivity to blue light at 1 degree eccentricity. Blue cone spacing may limit resolution of the blue channel out to 20-30 degrees eccentricity. The blue and red/green mosaics appear to be formed by separate processes.

Adolescent

Human photoreceptor topography.

We have measured the spatial density of cones and rods in eight whole-mounted human retinas, obtained from seven individuals between 27 and 44 years of age, and constructed maps of photoreceptor density and between-individual variability. The average human retina contains 4.6 million cones (4.08-5.29 million). Peak foveal cone density averages 199,000 cones/mm2 and is highly variable between individuals (100,000-324,000 cones/mm2). The point of highest density may be found in an area as large as 0.032 deg2. Cone density falls steeply with increasing eccentricity and is an order of magnitude lower 1 mm away from the foveal center. Superimposed on this gradient is a streak of high cone density along the horizontal meridian. At equivalent eccentricities, cone density is 40-45% higher in nasal compared to temporal retina and slightly higher in midperipheral inferior compared to superior retina. Cone density also increases slightly in far nasal retina. The average human retina contains 92 million rods (77.9-107.3 million). In the fovea, the average horizontal diameter of the rod-free zone is 0.350 mm (1.25 degrees). Foveal rod density increases most rapidly superiorly and least rapidly nasally. The highest rod densities are located along an elliptical ring at the eccentricity of the optic disk and extending into nasal retina with the point of highest density typically in superior retina (5/6 eyes). Rod densities decrease by 15-25% where the ring crosses the horizontal meridian. Rod density declines slowly from the rod ring to the far periphery and is highest in nasal and superior retina. Individual variability in photoreceptor density differs with retinal region and is similar for both cones and rods. Variability is highest near the fovea, reaches a minimum in the midperiphery, and then increases with eccentricity to the ora serrata. The total number of foveal cones is similar for eyes with widely varying peak cone density, consistent with the idea that the variability reflects differences in the lateral migration of photoreceptors during development. Two fellow eyes had cone and rod numbers within 8% and similar but not identical photoreceptor topography.

Cell Count

Computer methods for sampling, reconstruction, display and analysis of retinal whole mounts.

We are quantifying the distribution of photoreceptors and ganglion cells in human retina with the goal of establishing a reliable anatomical database which may be compared to information about visual function. We required a representation of retinal cell distributions which facilitated collection, analysis, and display of morphometric data from the entire retina of a large number of eyes. We report computer methods to (1) reconstruct the original retinal sphere from a three-piece whole mount preparation; (2) sample the retina in a manner which allowed description of approximately radially symmetrical cell distributions and avoided both undersampling (which produces interpolation artifacts) and oversampling (which wastes time); (3) interpolate between data points in order to produce plots of cell density along arbitrary meridians and maps of average cell density from several eyes; (4) specify locations on the retinal surface using a spherical coordinate system with its primary axis through the fovea; and (5) produce color-coded maps of cell distributions in a standard perimetric projection.

Cell Count

Distribution of cones in human and monkey retina: individual variability and radial asymmetry.

The distribution of photoreceptors is known for only one complete human retina and for the cardinal meridians only in the macaque monkey retina. Cones can be mapped in computer-reconstructed whole mounts of human and monkey retina. A 2.9-fold range in maximum cone density in the foveas of young adult human eyes may contribute to individual differences in acuity. Cone distribution is radially asymmetrical about the fovea in both species, as previously described for the distribution of retinal ganglion cells and for lines of visual isosensitivity. Cone density was greater in the nasal than in the temporal peripheral retina, and this nasotemporal asymmetry was more pronounced in monkey than in human retina.

Animals

Computer-assisted morphometry using video-mixed microscopic images and computer graphics.

A microcomputer system has been developed for collection and analysis of morphometric data from video images of histological sections. Microscopic fields of view are visualized on a video monitor and are overlaid with computer-generated graphics by means of a video mixer. Planimetric data are entered by drawing on a digitizing tablet while observing the drawn image superimposed on the tissue. Programs are available to calculate various geometric parameters, count objects in a field, perform descriptive statistics, and measure volume and surface area of a solid from a series of cross sections. A program for point-counting stereology presents single points for scoring within a user-defined reference area. The potential applications of interactive graphics in morphometry are discussed.

Cell Nucleus

A computer system for combined neuronal mapping and morphometry.

A computer system has been developed which allows both mapping and planimetry of histological preparations. Data consist of cytoarchitectonic boundaries defined in low-power micrographs of thick sections, and nuclear and vascular profiles defined in high-power micrographs of semi-thin sections taken from the original thick tissue, and landmarks common to both. Data from these different preparations and magnifications are entered into the computer on a digitizing tablet and are stored as points in a real-world coordinate system, along with profile labels, landmarks for alignment purposes, and section depth. Subsequent programs determine parameters such as area and perimeter for each profile, as well as its geometric center and relationship to the cytoarchitectonic boundary. This mapping parameter allows morphometric analysis of profiles as a function of their position. Other programs allow display and manipulation of data in 3 dimensions, cell counts, and stereology. Data acquisition is done in the laboratory, using a micro-computer; analysis and display are done on a large time-sharing computer connected to the small machine by a telephone interface.

Animals