Excess lead in the neural retina in age-related macular degeneration.

PURPOSE: To measure lead and cadmium in retinal tissues of human donor eyes with and without age-related macular degeneration (AMD). DESIGN: Laboratory investigation. METHODS: Lead and cadmium concentrations in retinal tissues (neural retina and retinal pigment epithelium [RPE]-choroid complex) in 25 subjects with AMD (50 donor eyes) and 36 normal subjects (72 donor eyes) were determined by using inductively coupled plasma-mass spectrometry. Severity of AMD was graded by using color fundus photographs and the Minnesota Grading System. Differences in metal concentrations were compared by using Wilcoxon rank-sum tests. RESULTS: The neural retinas of subjects with AMD had increased lead concentrations (median, 12.0 ng/g; 25% to 75% interquartile range, 8 to 18 ng/g; n = 25) compared with normal subjects (median, 8.0 ng/g; 25% to 75% interquartile range, 0 to 11 ng/g; P = .04; n = 36). There was no difference in lead concentration in the RPE-choroid complex between subjects with AMD (median, 198 ng/g; 25% to 75% interquartile range, 87 to 381 ng/g) and normal subjects (median, 172 ng/g; 25% to 75% interquartile range, 100 to 288 ng/g; P = .25). Cadmium concentration in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.8 microg/g) and RPE-choroid complex (median, 2.2 microg/g; 25% to 75% interquartile range, 1.8 to 3.7 microg/g) in subjects with AMD was not different from concentrations in the neural retina (median, 0.9 microg/g; 25% to 75% interquartile range, 0.7 to 1.4 microg/g; P = .32) and RPE-choroid complex (median, 1.5 microg/g; 25% to 75% interquartile range, 0.9 to 2.5 microg/g; P = .12) of normal subjects. CONCLUSIONS: AMD is associated with excess lead in the neural retina, and this relationship suggests that metal homeostasis in AMD eyes is different from normal.

Reduced zinc and copper in the retinal pigment epithelium and choroid in age-related macular degeneration.

PURPOSE: To measure zinc and copper levels in the retinal pigment epithelium (RPE) and choroid complex and in the neural retina in subjects with and without age-related macular degeneration (AMD). DESIGN: Laboratory investigation. METHODS: Eighty-eight donor eyes (44 subjects) were analyzed. After retinal dissection, the RPE and choroid complex was photographed. Using the Minnesota Grading System (MGS), the RPE and choroid complex was classified into 1 of 4 stages as defined by the Age-Related Eye Disease Study. Subjects without AMD were defined as both eyes having MGS stage 1; subjects with AMD were defined as both eyes having MGS stages 2 through 4. Zinc and copper levels were determined by using an inductively coupled plasma-mass spectrometer. Metal levels from two eyes of the same subject were averaged and treated as one observation. Differences in metal levels were examined by using Wilcoxon rank-sum tests. RESULTS: The mean RPE and choroid complex zinc level in subjects with AMD (+/- standard deviation, 223.7 +/- 94.0 microg/g; n = 15) was reduced 24% when compared with that of subjects without AMD (292.1 +/- 98.5 microg/g; n = 29; P = .01). The mean RPE and choroid complex copper level in subjects with AMD (5.1 +/- 1.1 microg/g) was reduced 23% when compared with that of subjects without AMD (6.6 +/- 1.4 microg/g; P = .002). No difference was detected in retinal zinc and copper levels in subjects with and without AMD (P > .09). CONCLUSIONS: Reduced RPE and choroid complex zinc and copper levels in AMD eyes combined with previous information that oral supplementation of zinc plus copper reduces the risk of progression of AMD suggests that metal homeostasis plays a role in AMD and in retinal health.

Clinical significance of the laboratory determination of low serum copper in adults.

BACKGROUND: Low serum copper is often indicative of copper deficiency. Acquired copper deficiency can cause hematological/neurological manifestations. Wilson disease (copper toxicity) is associated with neurological manifestations and low serum copper, with copper deposited in tissues responsible for the toxicity. Low serum copper can also be observed in some carriers of the Wilson disease gene and aceruloplasminemia. This study was undertaken to determine the clinical significance of low serum copper. METHODS: The Mayo Medical Laboratories', Metals Laboratory database was reviewed over a 9-month period to identify patients who received their care at the Mayo Clinic and had low serum copper. The medical records were analyzed to determine the significance of the low copper. RESULTS: In six of the 57 patients with low serum copper, the low copper was due to Wilson disease. In the remaining 51 patients, copper deficiency due to an underlying cause was identified in 38 as a reason for the low serum copper. The most commonly identified neurological manifestation of copper deficiency was myeloneuropathy. Coexisting nutrient deficiencies and hematological manifestations of copper deficiency were often but not invariably present. CONCLUSIONS: Copper deficiency, Wilson disease (or a carrier state), and aceruloplasminemia are all associated with low serum copper. The presence of coexisting neurological or hematological manifestations that are recognized sequelae of copper deficiency should be considered prior to making a diagnosis of copper deficiency. Gastrointestinal disease or surgery is a common cause of acquired copper deficiency. Even in patients in whom low serum copper is indicative of copper deficiency, the cause of the copper-deficient state may not be evident.

Urinary cadmium and age-related macular degeneration.

PURPOSE: To evaluate the association between urinary and blood cadmium (Cd) levels with age-related macular degeneration (AMD). DESIGN: Prospective case-control study. METHODS: In 53 participants older than 60 years with AMD in both eyes and in 53 age-matched (+/- 3 years) controls without AMD, Cd levels were measured in blood and urine specimens (with and without creatinine adjustment) by using inductively coupled plasma-mass spectrometry. Data on age, gender, smoking status, and family history were obtained. By using color stereoscopic fundus photographs, the degree of AMD was graded using the Age-Related Eye Disease Study's 4-stage AMD severity scale. The inclusion criterion for AMD cases was a photographic severity level of two to four in both eyes. Median blood and urine Cd and median urine Cd/creatinine concentrations in cases and controls were compared by using the rank-sum test, stratifying for smoking status. RESULTS: Current and former smokers with AMD had median urine Cd/creatinine levels (1.18 microg/g; range, 0.84 to 1.44 microg/g) that were 97% higher than smokers without AMD (0.60 microg/g; range, 0.49 to 0.90 microg/g; P = .02), 111% higher than never smokers with AMD (0.56 microg/g; range, 0.40 to 0.80 microg/g; P < .001) and 107% higher than never smokers without AMD (0.57 microg/g; 0.40 to 0.65 microg/g; P < .001). Blood Cd levels, indicative of short-term exposure levels, were not associated with AMD (P >/= .06). CONCLUSIONS: A higher urinary Cd level, which reflects the total body burden of Cd, was associated with AMD in smokers. Accumulated Cd exposure may be important in the development of smoking-related AMD.

Heavy metal concentrations in human eyes.

PURPOSE: To measure the concentration of toxic heavy metals in the fluids and tissues of human eyes. DESIGN: Laboratory investigation. METHODS: Thirty autopsy eyes of 16 subjects were dissected to obtain the aqueous, vitreous, lens, ciliary body, retina, and retinal pigment epithelium/choroid. Concentrations of lead, cadmium, mercury, and thallium in ocular tissues, ocular fluids, and blood were determined using an inductively coupled plasma-mass spectrometer and expressed as ng/g. Heavy metal concentrations in ocular tissues were compared using a paired t test. RESULTS: Lead and cadmium were found in all of the pigmented ocular tissues studied, concentrating to the greatest extent in the retinal pigment epithelium/choroid (mean, 432 +/- 485 ng/g and 2,358 +/- 1,522 ng/g). Cadmium was found in the retina in all eyes (mean, 1,072 +/- 489 ng/g) whereas lead was found in the retina in 9 (30%) of 30 eyes (mean, 53 +/- 54 ng/g). Trace concentrations of lead and cadmium were detected in the vitreous (mean, 0.5 +/- 1.0 ng/dl and 19 +/- 29 ng/dl), lens (mean, 13 +/- 18 ng/g and 20 +/- 18 ng/g), and blood (mean, 0.5 +/- 1.2 mug/dl and 3.1 +/- 4.1 mug/l) but were not detected in the aqueous. Mercury and thallium were not detected in any ocular tissues or fluids or in the blood. CONCLUSIONS: Lead and cadmium accumulate in human ocular tissues, particularly in the retinal pigment epithelium and choroid. The potential ocular toxicity of these heavy metals and their possible role in eye disease requires further study.