Copper and zinc distribution in the human retina

Relationship to cadmium accumulation, age, and gender

N. K. Wills, V-M Ramanujam, N. Kalariya, J. R. Lewis, F. J G M van Kuijk

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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 (Bruch's 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 ∼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 (≥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.

Original languageEnglish (US)
Pages (from-to)80-88
Number of pages9
JournalExperimental Eye Research
Volume87
Issue number2
DOIs
StatePublished - Aug 2008

Fingerprint

Cadmium
Retina
Zinc
Copper
Retinal Pigment Epithelium
Metals
Choroid
Tissue Donors
Retinal Diseases
Bruch Membrane
Graphite
Poisons
Age Factors
Macular Degeneration
Tissue Distribution
Sex Characteristics
Mass Spectrometry
Spectrum Analysis
Cell Survival
Proteins

Keywords

  • cadmium
  • choroid
  • copper
  • human
  • neural retina
  • retinal pigment epithelium
  • zinc

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Copper and zinc distribution in the human retina : Relationship to cadmium accumulation, age, and gender. / Wills, N. K.; Ramanujam, V-M; Kalariya, N.; Lewis, J. R.; van Kuijk, F. J G M.

In: Experimental Eye Research, Vol. 87, No. 2, 08.2008, p. 80-88.

Research output: Contribution to journalArticle

Wills, N. K. ; Ramanujam, V-M ; Kalariya, N. ; Lewis, J. R. ; van Kuijk, F. J G M. / Copper and zinc distribution in the human retina : Relationship to cadmium accumulation, age, and gender. In: Experimental Eye Research. 2008 ; Vol. 87, No. 2. pp. 80-88.
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