Zinc and energy requirements in induction of oxidative stress to retinal pigmented epithelial cells.
In age-related macular degeneration (AMD), retinal pigmented epithelium (RPE) cells are believed to be detrimentally affected. It is thought that zinc may play a part in this process. In the past, therefore, zinc supplementation has been suggested as a treatment for AMD. Experimental data shown here confound this view by indicating that whereas low amounts of zinc do protect RPE cells in culture from stress-induced effects, greater amounts of zinc have the opposite influence. These effects are partly dependent upon the "health status" of the cells. Experimental data presented herein also show that zinc-induced death of RPE cells can, however, be attenuated by compounds such as antioxidants (alpha-tocopherol, trolox, and metipranolol), or cellular energy substrates (pyruvate and oxaloacetate). It is therefore concluded that a combination of zinc and antioxidants or energy substrates rather that zinc alone should provide a safer and more effective way to treat a disease such as AMD.
Nuffield Laboratory of Ophthalmology, University of Oxford, Walton Street, Oxford, United Kingdom GB-OX2 6AW.
John P M
JP
Wood
Neville N
NN
Osborne
D000975:Antioxidants / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002412:Cations; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism; D006801:Humans; D018384:Oxidative Stress; D010857:Pigment Epithelium of Eye / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015032:Zinc / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity
D000975:Antioxidants; D002412:Cations; D002614:Chelating Agents; D015032:Zinc; D002118:Calcium