title: Cadmium accumulation in the human retina: effects of age, gender, and cellular toxicity.
abstract: Tobacco smoking and aging are among the few factors linked to age-related macular degeneration (AMD), a major cause of blindness in the elderly. Recent studies indicate that cadmium (Cd), an environmental toxic trace metal, is approximately four-fold higher in the retinas of smokers compared to non-smokers. In this study, we determined the effects of age and gender on Cd accumulation in human retinal tissues, specifically the neural retina, retinal pigment epithelium (RPE), and choroid. Cadmium levels in cultured RPE cells or retinal tissues isolated from frozen donor eyes were measured using inductively coupled plasma mass spectrometry (ICP-MS) and graphite furnace atomic absorption spectrophotometry (GF-AAS). Cadmium uptake in cultured human RPE cells (ARPE-19) was also assessed using GF-AAS. Toxic effects of cadmium were determined from cell loss (measured as a decrease in cell density) and lactate dehydrogenase release (an indicator of membrane disruption). In "young" eyes (< 55 years) Cd was highest in the retinal pigment epithelium and lowest in the neural retina. Cd was higher in all tissues in aged eyes (>or=55 years) and was significantly higher in the neural retina and RPE in older females. Cultured RPE cells exposed to Cd showed altered cell morphology, decreased cell survival, elevated ROS levels and concentration-dependent disruption of membrane integrity. We conclude that cadmium is accumulated differently in the neural retinal and RPE of older men and women. The deleterious effects of Cd on RPE cells indicate that this environmental toxin is a potentially important factor in age-related retinal disease.
authors.affiliation: Department of Neuroscience & Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA. nkwills@utmb.edu
authors.forename: N K
authors.initials: NK
authors.lastname: Wills
authors.forename: V M Sadagopa
authors.initials: VM
authors.lastname: Ramanujam
authors.forename: J
authors.initials: J
authors.lastname: Chang
authors.forename: N
authors.initials: N
authors.lastname: Kalariya
authors.forename: J R
authors.initials: JR
authors.lastname: Lewis
authors.forename: T-X
authors.initials: TX
authors.lastname: Weng
authors.forename: F J G M
authors.initials: FJ
authors.lastname: van Kuijk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D002104:Cadmium / Q000032:analysis* / Q000493:pharmacokinetics / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D018118:Chloride Channels / Q000187:drug effects; D002829:Choroid / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007223:Infant; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010857:Pigment Epithelium of Eye / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D012160:Retina / Q000737:chemistry* / Q000187:drug effects; D012737:Sex Factors; D013054:Spectrophotometry, Atomic / Q000379:methods
chemical_list: D018118:Chloride Channels; D002104:Cadmium; D007770:L-Lactate Dehydrogenase