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Biomedical subjects

Dirk van Norren

Publications and source records attributed to Dirk van Norren.

14 recordsLinked to original sources
PubMed2006

Retinal degeneration and ionizing radiation hypersensitivity in a mouse model for Cockayne syndrome.

Mutations in the CSB gene cause Cockayne syndrome (CS), a DNA repair disorder characterized by UV sensitivity and severe physical and neurological impairment. CSB functions in the transcription-coupled repair subpathway of nucleotide excision repair. This function may explain the UV sensitivity but hardly clarifies the other CS symptoms. Many of these, including retinopathy, are associated with premature aging. We studied eye pathology in a mouse model for CS. Csb(m/m) mice were hypersensitive to UV light and developed epithelial hyperplasia and squamous cell carcinomas in the cornea, which underscores the importance of transcription-coupled repair of photolesions in the mouse. In addition, we observed a spontaneous loss of retinal photoreceptor cells with age in the Csb(m/m) retina, resulting in a 60% decrease in the number of rods by the age of 18 months. Importantly, when Csb(m/m) mice (as well as Csa(-/-) mice) were exposed to 10 Gy of ionizing radiation, we noticed an increase in apoptotic photoreceptor cells, which was not observed in wild-type animals. This finding, together with our observation that the expression of established oxidative stress marker genes is upregulated in the Csb(m/m) retina, suggests that (endogenous) oxidative DNA lesions play a role in this CS-specific premature-aging feature and supports the oxidative DNA damage theory of aging.

Animals↗
PubMed2006

Influence of macular pigment and melanin on incident early AMD in a white population.

BACKGROUND: The protective effect of macular pigment (MP) and melanin against age-related macular degeneration (AMD) is still controversial from cross-sectional studies. In an attempt to clarify this issue, we performed a population-based longitudinal study. METHODS: MP optical density (MPOD) and melanin optical density (MOD) data were collected during the second follow-up phase of the Rotterdam Study in 1999 in a random subset of 435 participants. Data from 419 participants (98% white) was available for analysis. AMD diagnosis was based on standardized fundus photographs according to the International Classification System, and AMD cases were subdivided into five mutually exclusive stages. In the three follow-up phases, incident AMD (iAMD), defined as absence of any AMD at baseline and the presence of stage 2 or higher at follow-up, was determined. We used Cox regression analysis to study the effect of an assumedly stable MPOD and MOD on early iAMD. RESULTS: During a mean follow-up of 9.82 years, 13 male and 17 female participants developed early iAMD and two male participants late iAMD. Because only two participants developed late iAMD, we had to restrict our analyses to early iAMD. Cox regression analysis adjusted for age and gender showed no significant effect of MPOD [hazard ratio (HR) 0.37; 95% confidence interval (CI) 0.04, 3.57] and MOD (HR 0.56; 95% CI 0.09, 3.60) on early iAMD. Additional adjustment for smoking did not change these associations. CONCLUSIONS: This unique but quantitatively limited material leads to the conclusion that no major protective effect of MPOD or MOD was seen on early iAMD.

Antioxidants↗
PubMed2006

Macular pigment shows ringlike structures.

PURPOSE: The spatial distribution of macular pigment is generally assumed to monotonously decrease to very low values in the periphery. However, there are indications that this picture may be too simple. The purpose of this study was to examine the spatial distribution of the macular pigment optical density. METHODS: Fundus reflectance and autofluorescence maps at 488 and 514 nm Argon laser wavelengths were acquired in 53 healthy subjects with a custom-built scanning laser ophthalmoscope. Because the lens and the macular pigment are the only absorbers in this wavelength region, digital subtraction of log reflectance and log autofluorescence at the two wavelengths provides density maps of the sum of both absorbers. RESULTS: In approximately half of the subjects, we observed a distinct ring pattern at a mean distance of 0.7 degrees of the fovea. In a few subjects, the ring had an even larger optical density than did the central peak. A simple model with an exponentially decaying density as a function of eccentricity, in combination with a Gaussian-distributed ring pattern, yielded a good description of the data for both methods. The widths of the central peak and the Gaussian ring, and also the eccentricity at which the ring peaks, were similar for both methods. The prominence of the ring did not depend on age and gender. CONCLUSIONS: Both reflectance and autofluorescence maps showed ring patterns in the distribution of the macular pigment, which probably follow the inner plexiform layer.

Adult↗
PubMed2005

On the age dependency of the macular pigment optical density.

Macular pigment may protect against age related macular degeneration (AMD), because of its capability to absorb blue light and scavenge free radicals. Since age is the major risk factor in AMD, a fundamental question to be answered is the possible age dependence of the macular pigment optical density (MPOD) in normal healthy subjects. In this study we used five methods to study a possible age effect: heterochromatic flickerphotometry, two setups for fundus reflectance spectroscopy, a Scanning Laser Ophthalmoscope (SLO) for obtaining reflectance, and the same SLO for autofluorescence maps. MPOD was determined from the reflected light by a full spectral analysis. We also used a new, directional analysis of the reflected light to estimate MPOD. The latter avoids the disturbing influence of stray-light. Digital subtraction at two wavelengths of log reflectance and digital subtraction of log autofluorescence obtained with the SLO provided MPOD maps. Together, all methods of measuring and of analysis provided seven MPOD estimates per subject. A total of 53 subjects, aged 19-76 years, completed all five measurements (and thus seven analyses). An additional 81 subjects, aged 18-70 years, were measured with one setup for fundus reflectance spectroscopy (and thus only two analyses). We could not find any association with age with all the objective techniques. Only MPOD values obtained with heterochromatic flickerphotometry showed a small, but significant decrease with age. This decrease was caused by an increase in the parafoveal data, suggesting that the central MPOD is unchanged with age. The bivariate correlation coefficients between all methods were significant (all p<0.001).

Adult↗
PubMed2005

A yellow ring-shaped macular reflection.

PURPOSE: To describe a yellow ring-shaped reflection in the macula of healthy subjects observed with a common indirect ophthalmoscope. DESIGN: Observational case series. METHODS: Fundus photographs of the macula were acquired with a slit lamp and 90-diopter lens in 5 healthy subjects (age range, 23-50 years) at a perpendicular angle and at an oblique angle to the retina. RESULTS: The perpendicular fundus photographs showed a yellow ring-shaped reflection with a diameter of approximately 5 degrees. The oblique photographs had a dark red spot in the center. CONCLUSIONS: To our knowledge, this phenomenon has hitherto escaped attention in the literature. We conclude that the shape, size, and location of the yellow reflection are consistent with a cone origin. This observation may be used for diagnostic purposes.

Adolescent↗
PubMed2005

Spectral and directional reflectance of the fovea in diabetes mellitus: photoreceptor integrity, macular pigment and lens.

Our aim was to assess the integrity of the photoreceptors in the fovea, and to measure the optical density of the macular pigment and the eye lens in patients with diabetes mellitus, and to compare the results with those of a group of healthy subjects. The directional and spectral properties of the light reflected from a 1.9 deg field centered on the fovea were measured simultaneously, in a single one second flash, with the Foveal Reflection Analyzer. The directional characteristics, i.e., the optical Stiles-Crawford effect, provided information on the integrity of the foveal photoreceptors. Model analysis of the spectral reflectance yielded optical densities of the macular pigment and the lens. The amplitude of the directional reflectance in diabetic eyes was significantly lower compared to controls (P<0.001). This indicates that the integrity of the photoreceptors in the fovea was altered in diabetics. Surprisingly, the directionality (a measure for the peakedness) was similar in diabetics and controls (P=0.3). The density of macular pigment was not different from that in controls (P=0.3). The optical density of the lens increased with age in both groups, but the rate of increase was larger in the diabetics (P<0.05). Possibly, the lens optical density increasing at a higher rate with age reflects changes preceding cataract formation.

Adult↗
PubMed2004

Thermal cataract, from furnaces to lasers.

BACKGROUND: Thermal cataract has long been known as an occupational disease in furnace workers. This affliction has virtually disappeared in western countries due to improved working conditions. However, new light sources have appeared on the scene, in particular lasers, which might also be capable of producing thermal cataract. The aim of this survey is to review the history and describe the present state of knowledge. METHODS: Experimental work, mainly on rabbits, was reviewed and complemented with the results of calculations on the thermal changes in the ocular media. RESULTS: Safe exposure limits were derived over the optical spectrum from the near ultraviolet to the far infrared. CONCLUSIONS: Lasers may be a cause of thermal cataract only in the near ultraviolet. Moreover, in this field of research too, it is concluded that science may be regarded as the present state of misunderstanding.

Animals↗
PubMed2004

Absorption of the eye lens and macular pigment derived from the reflectance of cone photoreceptors.

We measured the amplitude of the directional component of the bleached fundus reflectance, the so-called optical Stiles-Crawford effect, as a function of wavelength. The directional reflectance originates from within the outer segments of the photoreceptors. Thus only two anterior absorbers are of importance: macular pigment and the crystalline lens. Analysis of spectra obtained in pseudophakes established that the cone photoreceptors act as spectrally neutral reflectors. The reflectance spectra, expressed in density units, resembled the macular pigment density spectrum. Studying age effects in the lens of normal subjects resulted in a description of the optical density of the lens in terms of a "young" and an "aged" template. The young template represents the pigment O-beta-glucoside of 3-hydroxykynurenine, which dominates the light absorption in young eyes and decreases with age. The aged template represents the pigments accumulating in the lens with age. The total optical density increased with age, but it was lower in the wavelength region 500-650 nm than was previously assumed on the basis of psychophysical studies. Analysis of the spectra also provided precise individual estimates of the optical density of macular pigment. Finally, we observed a decrease in the photoreceptor reflectivity with age, possibly reflecting a degradation of the photoreceptors.

Adolescent↗
PubMed2003

Fundus reflectance--historical and present ideas.

In 1851 Helmholtz introduced the ophthalmoscope. The instrument allowed the observation of light reflected at the fundus. The development of this device was one of the major advancements in ophthalmology. Yet ophthalmoscopy allows only qualitative observation of the eye. Since 1950 attempts were made to address the challenging, quantitative assessment of the amount of light reflected by the fundus. At first, only comparative measurements were possible, applied in the study of macular and visual pigments. With improvements in light detecting techniques, and with the advent of microprocessors, the measurement of spectral and spatial distribution of the reflectance became feasible. This led to the development of models that explained the observed wavelength dependence and the directional behavior of light reflected from the fovea. The models allowed a quantitative assessment of many parameters on absorption and reflection by structures in the human eye. This paper provides a review of both the experimental and theoretical progress, and summarizes the results of fundamental and clinical research using fundus reflectometry.

Diagnostic Techniques, Ophthalmological↗
PubMed2003

Wavelength dependence of reflectometric cone photoreceptor directionality.

We present evidence for the wavelength dependence of the directionality of light reflected from cone receptor cells (optical Stiles-Crawford effect): Blue light is more directional than red. According to the waveguide-scattering model of Marcos et al. [J. Opt. Soc. Am. A 15, 2012 (1998)], directionality is the sum of a waveguide component and a scattering component. The latter is proportional to 1 over wavelength squared, and it is related to the row-to-row spacing of the cone lattice. Our results allow a firm confirmation of Marcos et al.'s theory. For a 1.9-deg foveal area, group mean (n = 18) cone spacing was 3.42 microm, in good agreement with anatomical data. Group mean waveguide directionality was 0.077 mm(-2).

Humans↗
PubMed2002

Simultaneous measurement of foveal spectral reflectance and cone-photoreceptor directionality.

An instrument for simultaneous measurement of foveal spectral reflectance and cone-photoreceptor directionality is described. The key element is an imaging spectrograph (spectral range of 420-790 nm) with its entrance slit conjugate to the pupil plane of a human eye. A 1.9-deg spot on the retina is sampled in 1 s. Video observation of the retina and the pupil facilitates proper alignment. Measurements were performed on 21 healthy subjects. Model analysis of the spectra provided densities of photostable ocular absorbers. As an example, macular pigment and melanin are discussed in more detail. Spatial profiles exhibited the optical Stiles-Crawford effect, reflecting cone-photoreceptor directionality.

Adult↗
PubMed2002

Macular pigment and melanin in age-related maculopathy in a general population.

PURPOSE: It has been suggested that macular pigment (MP) and melanin may protect against age-related maculopathy (ARM). To check this, MP and melanin optical density were measured in a random population-based sample of subjects 55 years of age or older. METHODS: Spectral fundus reflectance of the fovea was measured in one eye per subject in a 2.3 degrees detection field with a fundus reflectometer. The sample consisted of 199 men and 236 women. Analysis with a fundus reflectance model yielded individual estimates for the MP and melanin optical density. Diagnosis of ARM was based on grading of standardized fundus transparencies. Eyes were stratified in four exclusive stages of ARM. RESULTS: MP optical density (at 460 nm) was 0.33 +/- 0.15 in eyes without ARM (n = 289) and 0.33 +/- 0.16 in eyes at any stage of ARM (n = 146). Melanin optical density (at 500 nm) was 1.18 +/- 0.19 in eyes without ARM and 1.20 +/- 0.21 in eyes at any stage of ARM. We found no gender differences for either MP or melanin optical density. CONCLUSIONS: No differences in MP and melanin optical density were found between eyes with and without ARM or between the various ARM stages.

Aged↗
PubMedDate not supplied

Fast assessment of the central macular pigment density with natural pupil using the macular pigment reflectometer.

We built a new macular pigment reflectometer (MPR) for fast and objective measuring of the optical density of macular pigment in the human eye, using the undilated eye. The design is based on the spectral reflectance from a spot of white light at the fovea. To evaluate its performance, we measured the macular pigment of 20 healthy subjects, ages 18 to 79 years, under four conditions: (1) natural pupil in the dark, (2) natural pupil with dim room light, (3) dilated pupil in the dark, and for comparison with a different technique, (4) heterochromatic flicker photometry (HFP) in dim room light with natural pupil. Condition 1 was repeated in a subset of 10 subjects after an interval of at least 3 days. Data analysis with a model of reflectors and absorbers in the eye provided the density of the macular pigment in conditions 1 to 3. Dim room light and pupil dilatation had no influence on measured density. Mean within subjects variation was typically 7%. Mean difference between test and retest after at least 3 days was 1%. Correlation between MPR and HFP was r=0.56 (p=0.012). Mean within subjects variation with HFP was 19%. The new instrument holds promise for specific applications such as epidemiological research.

Computer Systems↗