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U.A. Schraermeyer, N. Kociok, H. Janicki, T. Lamah, I. Semkova, D. Kokkinou, H.U. Kasper, B. Kirchhof; Zinc Metabolism Dependends on Fundus Pigmentation - Concept of a New Strategy for Treatment of Amd . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4230.
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Purpose: In human eyes high amounts of zinc are stored in melanin containing cells. Zinc is important for normal retinal function and influences more than 300 enzymes. One of them is catalase which is involved in anti-oxidative defence mechanisms. Age related macula degeneration is associated with lack of zinc and decrease of catalase activity and melanin fundus pigmentation. Substitution with zinc did not show clear therapeutic effects in patients with AMD. We investigated whether zinc metabolism and its functional effects on gene expression are dependent on pigmentation. Methods: Albino (Wistar) and pigmented (Long Evans) rats were injected intraperitonealy with 40 mg/Kg ZnCl2.. After 24 h the choroid-RPE-complex was isolated from retina and sclera. Specimen from untreated animals were used as controls. In the first experiment samples are weighed (Microbalance Sartorius MC21S) directly into 7ml tightly closing PFA-vessels (Savillex) and digested (24h/30oC, ultrasonic homogenization) with HNO3-H202 suprapur grade reagents (Merck). After gentle evaporation the residue is dissolved in HNO3 2 % over 5 h at 50oC. This solution is transferred to a 10ml volumetric flask. The final clear solution containing 10ng Rh.ml-1 is filled up with HNO3 2%. Determination were performed by inductively coupled plasma mass spectrometry (ICP-MS, ELAN 6000 Perkin-Elmer/Sciex) using Rh as internal standard and a high purity chemical reagent calibration. In a second experiment the mRNA from such samples were isolated after 6 and 24 h. The amount of catalse mRNA was quantified by Real-Time RT-PCR. Results:The zinc content in choroid-RPE complex of untreated albino rats was 5.1 µg/g and 74 µg/g of pigmented rats and did not raise in tissues from albinos (6.5µg/g) but raised 1.6 fold (125 µg/g) in pigmented rats 24 h after injection of zinc. In choroid and RPE of albino rats the amount of mRNA for catalase did not increase 6 h after zinc substitution. However, in pigmented rats the amount of mRNA for catalase raised 12 fold after 6 h Conclusions:. Our results show that base level and uptake of zinc strongly depends on the degree of pigmentation. Only in pigmented choroid and RPE a strong upregulation of catalase mRNA by zinc treatment was observed. These results may explain why substitution of patients suffering from AMD and low fundus pigmentation with zinc was not yet successful. Overexpression of tyrosinase by gene therapy will enhance fundus pigmentation and may protect photoreceptors in combination with oral zinc substitution
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