F.J.G.M. van Kuijk

A portable instrument for measuring macular pigment with central fixation.

Purpose. To evaluate the reliability and validity of a portable instrument for measuring macular pigment optical density. Methods. The instrument is small, uses light emitting diodes as light sources and the principles of heterochromatic flicker photometry of comparing foveal and extra-foveal minimum flicker matches. It uses central fixation for the extra-foveal matches, which subjects found easier than eccentric fixation. Subjects with healthy eyes used the instrument to measure their pigment density in a number of eye clinics. Results. The mean pigment density in 124 eyes in 124 individuals was 0.41 ± 0.16 (mean ± SD), there was no significant change with age but the density was less in females, those with light irides, smokers, subjects on diets low in precursor carotenoids and in those exposed to several hours of daylight every day or who used sun beds. Conclusions. The portable instrument gave valid and reliable data that confirmed published values for macular pigment. It was convenient to use in the clinic and has potential as a screening tool.

Copper and zinc distribution in the human retina: Relationship to cadmium accumulation, age, and gender

The essential metals copper and zinc play vital roles in retinal cell survival and are crucial for the normal functioning of antioxidant enzymes. Retinal zinc deficiencies and decreased cellular antioxidative capacity have been linked to human retinal diseases including age-related macular degeneration (AMD). We recently reported that cadmium (a toxic metal with no known physiological function that interferes with copper and zinc metabolism) accumulates in human retinal tissues during aging. Moreover, cadmium content was higher in specific retinal tissues of aged women compared to men. Since cadmium, zinc and copper bind to similar proteins, we hypothesized that Cu and Zn content of human retinal tissues change as functions of cadmium accumulation during aging. Thus, we assessed the distribution of zinc and copper in the neural retina, retinal pigment epithelium (RPE) and choroid (Bruchs membrane-choroid; BMC) in male and female donors aged 1.5-87 years. Two independent methods, graphite furnace atomic absorption spectrometry and inductively-coupled plasma mass spectrometry, were used to measure Cd, Zn, and Cu in retinal tissues in human eyes from donors aged 1.5 to 87 years and the resulting values were normalized to protein concentration. Zn levels were approximately 5 times higher than Cu levels in the same tissues. The relative tissue distributions of these metals were: BMC>RPE>neural retina (Zn) and BMC>RPE=neural retina (Cu). In the choroid, mean Cu and Zn levels were higher in aged donors (>or=55 years old) than young donors (<55 years) and levels of these metals were strongly correlated with each other (r=0.90). In the neural retina, Cu and Zn both significantly decreased as a function of age. Several sex-related differences were found in the RPE. Specifically, copper levels were significantly higher in males than in females. In addition, both Zn and Cu levels in males were positively correlated with cadmium content, whereas this association did not occur in females. The results are consistent with co-regulation of zinc and copper stores in retinal tissues and suggest that the balance of these metals is associated with cadmium accumulation and gender. Thus, the roles of cadmium and gender differences in retinal metal balance warrant further investigation as factors in age-related retinal disease.

Metarhodopsin III formation and decay kinetics: comparison of bovine and human rhodopsin.

Absorbance spectra were recorded at various times after photolysis of hypotonically washed membrane suspensions of human and bovine rhodopsin (pH 7 or 8, T = 20 or 37 degrees C). Global data analysis showed that at 20 degrees C, metarhodopsin III formation was the only process occurring from 1 to 30 min following photolysis. At pH 8, a significant amount of human metarhodopsin I was present before metarhodopsin III formed. At 37 degrees C, two decay processes were seen, formation of metarhodopsin III (lifetime 113 +/- 3 sec bovine, 93 +/- 2 sec human) and formation of a species with the properties of n-retinylidine opsin (lifetime 900 +/- 150 sec bovine, 2000 +/- 350 sec human). A larger fraction of human rhodopsin (approximately 50%) is converted to metarhodopsin III than is the case for bovine rhodopsin (approximately 35%).

Human retinal cadmium accumulation as a factor in the etiology of age-related macular degeneration

Cadmium is a naturally occurring, highly toxic, metallic element. It pollutes the environment as a result of industrial activity and accumulates in human tissues with a long biological half-life. Cadmium content has been demonstrated to increase in human retinal tissues as a function of age and tobacco smokers have approximately twice as much cadmium in retinal tissues than non-smokers. Smoking is also a key environmental risk factor for the retinal disease age-related macular degeneration (AMD). Recent studies have shown that urinary cadmium levels (a measure of Cd body burden) are higher in smokers who have AMD. We now report the Cd measurements in human retinal tissues from eyes afflicted with AMD compared to non-diseased eyes (controls) from age-matched donors. Human donor eyes frozen under argon gas were assessed for AMD severity using color stereoscopic fundus photographs and the Minnesota Grading System. Cadmium, zinc and, copper levels were measured in retinal tissues (neural retina, retinal pigment epithelium and choroid) using inductively coupled plasma mass spectrometry and graphite furnace spectrophotometry and values were normalized to tissue protein levels. Higher Cd levels were found in the neural retina and RPE for eyes afflicted with AMD compared to controls in males, differences were not statistically significant in females. The results indicate that higher retinal cadmium burdens are associated with the presence of AMD at least in males and suggest possible gender differences in the metabolism of metals in the human retina.

Makuläres Pigment und altersabhängige Makuladegeneration

ZusammenfassungAuf Grund der pathogenetischen Vorstellungen für die Entstehung einer AMD wird ein negativer Einfluss und eine Mitverursachung der lebenslangen Lichtexposition mit Induktion oxidativer Veränderungen in den Photorezeptoren postuliert. Eine direkte kausale Verknüpfung dieser Faktoren konnte bisher noch nicht gelingen, doch stützen viele epidemiologische und experimentelle Untersuchungen diese Hypothese. Da das makuläre Pigment bestehend aus Lutein und Zeaxanthin durch seinen filternden Effekt und seine direkte antioxidative Wirkung der effektivste Lichtschutz in der zentralen Netzhaut ist (“natürliche Sonnenbrille”), kommt ihm bei der Reduktion oxidativer Lichtschäden eine zentrale Bedeutung zu. Die Beobachtung, dass mit zunehmendem Lebensalter und insbesondere bei AMD-Patienten niedrigere Konzentrationen an makulärem Pigment gefunden wurden, deutet darauf hin, dass ein niedriger Gehalt an makulärem Pigment mit einem erhöhten Risiko für eine AMD einhergeht. Da Lutein und Zeaxanthin nur exogen aufgenommen werden können und insbesondere durch eine entsprechende Ernährung, evtl. auch durch eine Supplementation dieser Karotenoide eine Erhöhung der makulären Pigmentkonzentrationen erreicht werden kann, sind diese Untersuchungen von großer Bedeutung, um einen evtl. zu beeinflussenden Risikofaktor für die Entstehung einer AMD näher zu charakterisieren.AbstractThe present concepts of the pathogenesis of AMD include cummulative light damage by oxidative processes in the macular photoreceptors as enviromental co-factor for the developement of AMD. The direct causative connection of this hypothesis has still to be established but wide circumstantial evidence from epidemiological and basic scientific investigations are strongly supportive. Macular pigment consisting of lutein and zeaxanthin through there ability to filter light and by direct antioxidative properties, has been proposed as the most effective protective factor in the central retina (“natural sun glasses”) and could be important to reduce light induced oxidative retinal damage. The observation, that with age and especially in eyes with AMD lower concentrations of macular pigment could be found, can be interpreted that low macular pigment concentrations may be associated with higher risk for AMD. Through dietary intake and eventually with supplementation the concentration of macular pigment can be increased, and analysis of the correlation between macular pigment and AMD may be important to characterise a possible influencable AMD risk factor.