Biomedical subjects

C A Curcio

Publications and source records attributed to C A Curcio.

At least 19 recordsLinked to original sources

PubMed1998

The Alabama Age-Related Macular Degeneration Grading System for donor eyes.

PURPOSE: To develop a systematic method for identifying and grading age-related macular degeneration (ARMD) in human donor eyes, postmortem fundus appearance was compared with histopathologic assessment in eyes with a spectrum of age-related macular change. METHODS: Eyes without grossly visible, late ARMD were obtained from 8 cancer patients and 26 donors older than 50 years. Postmortem fundus appearance was graded for drusen and pigmentary change, using stereo color photographs. Eyes were processed and sectioned at 1 microm for histopathologic evaluation of macular retinal pigment epithelium-Bruch's membrane complex. The histologic diagnosis was compared with gross fundus appearance, clinical ophthalmic histories (n = 25), and clinical fundus photographs that were graded using the Wisconsin Age-related Maculopathy Grading System (n = 5). RESULTS: Ten eyes met histopathologic criteria for early ARMD. A similar proportion of eyes (27%-32%) was identified as affected by ARMD by other published histopathologic criteria. By choosing eyes with at least one druse larger than 125 microm in diameter or an area of pigment-clumping 500 microm in diameter that was visible in the postmortem fundus, ARMD cases were identified with 90% sensitivity and 95% specificity. CONCLUSIONS: The Alabama ARMD Grading System permits rational and standardized use of donor eyes in studies that are directed toward understanding the pathogenesis of ARMD.

Aged↗

PubMed1996

Photoreceptor loss in age-related macular degeneration.

PURPOSE: The authors showed previously that parafoveal rods, but not cones, decrease during the course of adulthood in donor eyes that were screened to exclude the grossly visible macular drusen and pigmentary disturbances typical of age-related macular degeneration (AMD). Because AMD begins in the parafovea, this selective loss of rods actually may be subclinical AMD not yet visible in the fundus. If so, AMD must have a predilection for rods over cones. The authors tested this hypothesis by determining the relative numbers of cones and rods in donor eyes with mid-to late-stage AMD and in age-matched controls. METHODS: Thirteen eyes (from seven donors) with grossly visible macular drusen and pigmentary disturbances were either wholemounted for photoreceptor counts or sectioned through the fovea for histopathology and carbonic anhydrase histochemistry to label red-green cones. Eyes were assigned to AMD or control groups on the basis of histopathology and clinical history. RESULTS: Five nonexudative AMD (NE-AMD) eyes from three donors showed sparing of foveal cones and loss of rods and cones in the parafovea. In two donors, rod loss exceeded cone loss at most parafoveal locations, and in one donor, rod density was normal and cone density was reduced. In eight exudative AMD (EX-AMD) eyes from five donors, photoreceptors surviving along the margins of and overlying disciform scars were largely cones. CONCLUSIONS: Photoreceptors are lost in NE-AMD as well as in the more severe exudative form, consistent with functional and clinical studies. The authors propose that rods die in older eyes without evidence of overt retinal pigment epithelial disease. In persons susceptible to AMD, the retinal pigment epithelium becomes dysfunctional. Secondarily, rod loss continues and cones begin to degenerate. Eventually, only degenerate cones remain; ultimately, all photoreceptors may disappear.

Aged↗

PubMed1993

Retinal ganglion cells in Alzheimer's disease and aging.

Optic nerve and retinal ganglion cell (GC) degeneration are possible explanations for the poor visual function reported in patients with Alzheimer's disease (AD). We investigated whether GC loss could be attributed to AD compared with control subjects by measuring the spatial density of GC (cells/mm2) with methods previously used to analyze the GC distribution of young normal retinas. Retinas from 4 autopsy-confirmed, severely demented patients with AD and 4 age- and sex-matched control subjects (ages, 66-86 yr for both groups) without history of dementing or ocular disease were prepared as unstained whole mounts. There was no evidence for loss of GC within the central 43 degrees of vision in patients with AD. The density of GC subserving the central 11 degrees of vision was reduced by one-fourth in both AD and control eyes compared with retinas from young adults, as was GC density in a wedge of nasal retina. This loss may contribute to deficits in visual function found in aged individuals, whether or not they have dementia.

Adult↗

PubMed1993

Aging of the human photoreceptor mosaic: evidence for selective vulnerability of rods in central retina.

PURPOSE: Because previous studies suggested degeneration and loss of photoreceptors in aged human retina, the spatial density of cones and rods subserving the central 43 degrees of vision as a function of age was determined. METHODS: Cones and rods were counted in 27 whole mounted retinas from donors aged 27 to 90 years with macroscopically normal fundi. Photoreceptor topography was analyzed with new graphic and statistical techniques. RESULTS: Changes in cone density throughout this age span showed no consistent relationship to age or retinal location, and the total number of foveal cones was remarkably stable. In contrast, rod density decreased by 30%, beginning inferior to the fovea in midlife and culminating in an annulus of deepest loss at 0.5 to 3 mm eccentricity by the ninth decade. Space vacated by dying rods was filled in by larger rod inner segments, resulting in a similar rod coverage at all ages. At the temporal equator, cone density declined by 23%, but rods were stable throughout adulthood. CONCLUSIONS: The stability of both rod coverage and rhodopsin content despite decreasing cell number suggests plasticity of the adult rod system and that age-related declines in scotopic sensitivity may be due to postreceptoral factors. There is no evidence for the massive loss of foveal cones required to explain even modest decrements in acuity, consistent with evidence that visual deficits at high photopic levels may be largely due to optical factors. Why the rods of central retina, which share a common support system and light exposure with the neighboring cones, are preferentially vulnerable to aging remains to be determined.

Adolescent↗

PubMed1992

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↗

PubMed1991

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↗

PubMed1990

Topography of ganglion cells in human retina.

We quantified the spatial distribution of presumed ganglion cells and displaced amacrine cells in unstained whole mounts of six young normal human retinas whose photoreceptor distributions had previously been characterized. Cells with large somata compared to their nuclei were considered ganglion cells; cells with small somata relative to their nuclei were considered displaced amacrine cells. Within the central area, ganglion cell densities reach 32,000-38,000 cells/mm2 in a horizontally oriented elliptical ring 0.4-2.0 mm from the foveal center. In peripheral retina, densities in nasal retina exceed those at corresponding eccentricities in temporal retina by more than 300%; superior exceeds inferior by 60%. Displaced amacrine cells represented 3% of the total cells in central retina and nearly 80% in the far periphery. A twofold range in the total number of ganglion cells (0.7 to 1.5 million) was largely explained by a similar range in ganglion cell density in different eyes. Cone and ganglion cell number were not correlated, and the overall cone:ganglion cell ratio ranged from 2.9 to 7.5 in different eyes. Peripheral cones and ganglion cells have different topographies, thus suggesting meridianal differences in convergence onto individual ganglion cells. Low convergence of foveal cones onto individual ganglion cells is an important mechanism for preserving high resolution at later stages of neural processing. Our improved estimates for the density of central ganglion cells allowed us to ask whether there are enough ganglion cells for each cone at the foveal center to have a direct line to the brain. Our calculations indicate that 1) there are so many ganglion cells relative to cones that a ratio of only one ganglion cell per foveal cone would require fibers of Henle radiating toward rather than away from the foveal center; and 2) like the macaque, the human retina may have enough ganglion cells to transmit the information afforded by closely spaced foveal cones to both ON- and OFF-channels. Comparison of ganglion cell topography with the visual field representation in V1 reveals similarities consistent with the idea that cortical magnification is proportional to ganglion cell density throughout the visual field.

Adult↗

PubMed1990

Development redistribution of photoreceptors across the Macaca nemestrina (pigtail macaque) retina.

Redistributions of monkey cones and rods during the first year after birth include a fivefold increase in peak foveal cone density from 43,000 to 210,000 cones/mm2, a decrease in the diameter of the rod-sparse area, and a two- to threefold decrease in peripheral photoreceptor density. Two weeks before birth, higher cone density is already apparent in the future fovea, as are the nasotemporal asymmetry in cone distribution, a higher density "cone streak" along the horizontal meridian, a large rod-sparse central fovea, and a ring of high rod density. Despite the early appearance of these basic patterns, photoreceptor distribution is not mature until 1 to 5 years postnatally. Total cones varied from 4 million at birth to 3.1 million in the average adult. The two oldest eyes had fewer cones, suggesting up to a 25% loss late in development. There were 60 to 70 million rods in the adult macaque retina and little evidence of postnatal changes in number. Neither of these small changes is sufficient to account for the reduction in peripheral photoreceptor density and both are in the wrong direction to explain increasing foveal density, ruling out a major role for either photoreceptor death or generation. Retinal area increased by a factor of 2.4 from 2 weeks before birth to adulthood. In contrast, the posterior pole of the retina was dimensionally stable throughout this period, with the distance between the fovea and optic disc varying nonsystematically from 3.37 to 4.05 mm. Retinal coverage of the globe was also stable at 48-60%. Thus postnatal growth can be ruled out as a factor in the density changes occurring in central retina. Adult retinas have a higher proportion of both cones and rods in midperiphery, whereas young retinas have a higher proportion of photoreceptors in far periphery. It appears that photoreceptors are radially redistributed from peripheral toward central retina during postnatal development, resulting in the marked increase in foveal cone density and the decrease in the eccentricity of the rod ring. Up to 13 weeks postnatally, midperipheral growth of the retina is substantial and increases with eccentricity. At later ages, expansion continues only in the very far periphery. Retinal growth appears sufficient to explain the decreases in peripheral rod and cone density with age. These and previous data strongly suggest that differentiated photoreceptors, with complex cytology and synaptic contacts, migrate toward the foveal center, explaining the increase in foveal photoreceptor density.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

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↗

PubMed1989

Photoreceptor topography of the retina in the adult pigtail macaque (Macaca nemestrina).

In spite of the crucial role retinal photoreceptors play in mapping optical images into a pattern of neural excitation, there are no complete studies of photoreceptor topography in any primate retina. We have measured the spatial density and inner segment areas of cones and rods across the whole mounted retinas of three adult pigtail macaques (Macaca nemestrina) and constructed maps of photoreceptor density and inner segment diameter. These retinas contain an average of 3.1 million cones (2.8-3.3 million), with an average peak foveal cone density of 210,000 cones/mm2 (190,000-260,000 cones/mm2). Cone density falls steeply with increasing eccentricity, to 100,000 cones/mm2 at 200 microns from the fovea, and to 50,000 cones/mm2 at 750 microns. Imposed on this gradient is a "streak" of higher cone density along the horizontal meridian. At equivalent eccentricities, cone density is higher in nasal and inferior retina. Cone inner segments increase in diameter from 2.3 microns at the foveal center to 11 microns in far temporal retina and 10 microns in far nasal retina. These retinas contain an average of 60.1 million rods (44.9-75.3 million). Rod density is zero within 20 microns of the foveal center, increases to the crest of a "rod ring" at the eccentricity of the optic disk, and then declines. Central rod topography is asymmetric, with higher densities in superior retina. Density along the crest of the rod ring peaks in superior retina at 177,000 rods/mm2, dips as low as 120,000 rods/mm2 along the horizontal meridian, and increases to about 150,000 rods/mm2 in inferior retina. Far peripheral rod topography is relatively symmetric around the fovea. Rod inner segment diameter ranged from 1.5 microns in the fovea to 4 microns at the temporal edge and 3.4 microns at the nasal edge of the retina. At eccentricities exceeding 6 mm, rod inner segment diameter was greater temporally than nasally. Cone inner segments cover 85-90% of the central fovea, with extrareceptor space accounting for the remainder. Cone coverage declines with increasing eccentricity to 20% at the temporal edge and 35% at the nasal edge of the retina. In contrast, rod coverage increases from zero at the foveal center to a maximum of 65% in temporal retina and 50% in nasal retina. The photoreceptor topography of the pigtail macaque is qualitatively similar to that of other macaques and to humans. Photoreceptor topography is formed by a complex interaction between regional changes in cone and rod density and inner segment diameter.

Animals↗

PubMed1989

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↗

PubMed1989

The spatial resolution capacity of human foveal retina.

An image on the retina of a human eye enters the visual system through an array of photoreceptors that sets the boundaries on the spatial detail available for neural representation. In order to investigate the extent to which the input spatial detail is preserved by the human neural system, we compare the anatomical spatial limits as determined by the Nyquist frequency, the highest spatial frequency reconstructable from the cone array, and measures of human acuity, the minimum angle resolvable. We find that the anatomical Nyquist limits determined along the temporal horizontal meridian of a well-studied human retina (Curcio, Sloan, Packer, Hendrickson & Kalina, 1987b) offer a reasonable prediction of human acuity within the retinal region extending from slightly off the exact foveal center to about 2.0 deg of retinal eccentricity. However, we find a narrow peak of anatomical resolution at the foveal center where the acuity appears to be overestimated by cone spacing.

Adult↗

PubMed1987

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↗

PubMed1987

A whole mount method for sequential analysis of photoreceptor and ganglion cell topography in a single retina.

Photoreceptors (PR) in human and monkey retina are visible in whole mounts cleared with glycerol or dimethyl sulfoxide and viewed with Nomarski differential interference contrast microscopy. These preparations substantially decrease the large tissue volume changes associated with dehydration and sectioning and reveal many details of PR organization and cytology with great clarity. Tissue may be subsequently stained to reveal ganglion cells so that the topography of both cell types may be studied in the same retina.

Animals↗

PubMed1987

Partial supracoronary translocation of the aortic valve prosthesis in a case of septic destruction of the aortic root.

A patient with infective endocarditis and septic disruption of the anterior aspect of the aortic root was successfully treated by insertion of a prosthetic valve obliquely, above the right coronary ostium anteriorly and below the left posteriorly. The right coronary ostium was closed and the artery was bypassed by use of an autogenous saphenous vein graft. The procedure is considered to be an alternative to the more radical complete supracoronary translocation of the prosthetic valve, as described by Danielson and colleagues.

Abscess↗

PubMed1987

Partial atrioventricular canal in an adult: mitral valve repair by reverse implantation of a Carpentier ring.

A severely incompetent mitral valve of partial atrioventricular canal type was repaired by reverse implantation of a Carpentier ring. The flat segment of the ring was adapted to the lateral leaflet of the valve and the curved segment to the combined left superior and left inferior leaflets. The so-called cleft was sutured. The procedure resulted in a fully competent mitral valve that continues to be competent 2 years after the operation.

Adult↗

PubMed1986

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↗

PubMed1985

Aging in the rat olfactory system: relative stability of piriform cortex contrasts with changes in olfactory bulb and olfactory epithelium.

Previous studies have quantified growth and atrophy of the olfactory bulb and olfactory epithelium of the Sprague-Dawley rat from maturity to senescence. Major events occurring in these structures include changes in the volume of mitral cells and changes in the number of septal olfactory receptors. These effects are large, consist of a growth phase followed by atrophy, and are temporally related in that events in the olfactory epithelium precede those in the mitral cells. A hypothesis of aging based on transneuronal effects would predict that these changes would be similarly transmitted to the next synaptic station in the olfactory pathway. Therefore, cells and synapses of the piriform cortex were studied in rats 3, 12, 18, 24, 27, 30, and 33 months of age. Alternate Vibratome sections through brains perfused with mixed aldehydes were processed for light and electron microscopy. No significant age effects were found for the volumes of cortical laminae Ia and Ib. Both numerical and surface density of synaptic apposition zones in layer Ia, formed primarily by mitral cell axons, were stable with age. A modest (18%) but significant decline in the proportion of layer Ia occupied by dendrites and spines was mirrored by an increase in the proportion of glial processes; no change in the proportion of axons and terminals was observed. Neither nuclear volume, nor soma volume, nor numerical density of layer II neurons changed with age. Thus, contacts made in the piriform cortex by mitral cell axons remain relatively stable in senescence, despite the marked volumetric changes in the mitral cell somata, changes which were confirmed again in this study. Age-related dendritic regression in layer II neurons may be attributable to functional deafferentation subsequent to reduced receptor input to mitral cells.

Age Factors↗