Biomedical subjects

C L Millican

Publications and source records attributed to C L Millican.

8 recordsLinked to original sources

PubMed2001

Accumulation of cholesterol with age in human Bruch's membrane.

PURPOSE: To determine the cholesterol composition of normal human Bruch's membrane and choroid as a function of age and retinal location. METHODS: Human eyes with grossly normal maculas were preserved <4 hours after donor death. Cryosections of retina and choroid from the macula and temporal equator were stained with filipin to reveal esterified (EC) or unesterified (UC) cholesterol (n = 20, 17-92 years). Filipin fluorescence in Bruch's membrane was quantified with digital microscopy. Maculas were prepared for lipid-preserving electron microscopy (n = 18, 16-87 years) and for ultrastructural analysis after lipid extraction (n = 2, 85 and 89 years). Punches of macular Bruch's membrane, 8 mm in diameter, were assayed for cholesterol content by enzymatic fluorometry (n = 10, >70 years). RESULTS: EC and UC in Bruch's membrane increased with age in the macula. EC was sevenfold higher in macula than in periphery. Sixty percent of total cholesterol was esterified, and Bruch's membrane EC was 16- to 40-fold enriched relative to plasma. Solid, 100-nm-diameter particles occupied >30% of the inner collagenous layer in eyes >60 years. Cholesterol accumulated in choroidal arteries and in small age-related drusen. CONCLUSIONS: Human Bruch's membrane ages like arterial intima and other connective tissues for which plasma lipoproteins are the known source of extracellular cholesterol. Age-related maculopathy and atherosclerotic cardiovascular disease may share common pathogenic mechanisms.

Adolescent↗

PubMed1999

Basal linear deposit and large drusen are specific for early age-related maculopathy.

OBJECTIVE: To determine the distributions of basal laminar and basal linear deposits in Bruch membrane (BM) with respect to age and early age-related maculopathy (ARM). METHODS: The foveas of 41 human eyes (<60 years [n = 9]; > or =60 years [n = 32]), preserved no later than 3.5 hours post mortem, were examined using light and electron microscopy. Ten eyes met histopathologic criteria of the Alabama Age-related Macular Degeneration Grading System for early ARM. We calculated the specificity, sensitivity, and odds ratios for the association of basal laminar and basal linear deposits with early ARM. RESULTS: Both deposits occurred only in eyes older than 60 years. The highest specificities and sensitivities for early ARM were attained for eyes that had basal linear deposits or large (>125 microm) drusen, followed by eyes with any quantity of basal laminar deposits that also contained membranous debris. Eyes with ARM were 24 times more likely than age-matched control eyes to have basal linear deposits or large drusen (P = .002). CONCLUSIONS: Basal linear deposits and large drusen with membranous contents constitute different morphologic forms of the same ARM-associated lesion and may be significant for progression to late ARM.

Adolescent↗

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

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↗

PubMed1987

Photopic spectral sensitivity of the cat.

1. The psychophysical spectral sensitivity of cats was assessed using a two-choice visual discrimination task by determining increment thresholds and critical flicker frequency on white and chromatic backgrounds. 2. For large increments, on 0.0, 0.3 and 3.0 cd/m2 white backgrounds, the cats were most sensitive to 497 nm indicating that these backgrounds are scotopic. On 30 and 300 cd/m2 white backgrounds, the cats were most sensitive to about 454 and 561 nm indicating that these backgrounds are photopic. Sensitivity to intermediate wave-lengths indicated independent action of 'blue' and 'green' cones. 3. For large increments, thresholds on photopic yellow and magenta backgrounds indicated the additive influence of 'blue' and 'green' cones. 4. Spectral sensitivity functions obtained with a critical flicker frequency criterion of 10 Hz on a 30 cd/m2 white background reflected only the activity of the 'green' cone while at 20 Hz the function reflected an additive contribution of both 'blue' and 'green' cones. 5. For small increments, on a 30 cd/m2 white or 96 cd/m2 orange background, sensitivity reflected only the activity of the 'green' cone. 6. The cat's photopic spectral sensitivity is influenced by the psychophysical test upon which it is based in a manner that is similar to what has been found for other vertebrates. No evidence was found for a 500 nm mechanism active at photopic levels.

Adaptation, Ocular↗

PubMed1983

Increment thresholds in normal and binocularly deprived cats.

Increment thresholds on a white background were determined for normal and binocularly deprived (BD) cats over a wide luminance range. Threshold vs intensity curves had a slope of unity for both groups but the increment threshold (delta I/I) for normal cats was 0.09 while increment threshold for BD cats was 0.60. Absolute threshold was reliably better in normal cats. the deficit of BD cats is considered a potential result of their abnormal cortical physiology and/or abnormal lateral geniculate physiology.

Animals↗

PubMed1981

Acuity, luminance, and monocular deprivation in the cat.

Visual acuity was determined for both eyes of long-term monocular-deprived cats over a wide luminance range. The influence of luminance on the rate of pattern vision recovery was also examined. Unlike strabismic humans and cats, the acuity deficit of monocularly deprived cats is not luminance dependent. This acuity is much worse at all luminance levels in the deprived eye. Likewise, initial testing of the deprived eye at low luminance levels does not facilitate recovery of pattern vision. Therefore, monocular lid fusion results in a visual deficit that differs from the effects of strabismus but resembles the effects of anisometropia in man.

Animals↗