Metallothionein shows an age-related decrease in human macular retinal pigment epithelium.

PURPOSE To investigate the possible role of zinc-metallothionein in human retinal pigment epithelium with regard to age-related changes. METHODS A cadmium/heme assay was used to quantitate metallothionein in isolated macular and peripheral retinal pigment epithelium from donors ranging in age from 28 to 91 yr (n = 16, mean age = 68.6 yr). RESULTS It was found that peripheral retinal pigment epithelium contained significantly more metallothionein and zinc than macular retinal pigment epithelium. Macular retinal pigment epithelium cells contained 17.6 +/- 2.2 micrograms metallothionein/mg cytosolic protein in donors younger than 70 yr, compared to 5.6 +/- 0.9 in macular retinal pigment epithelium from donors older than 70 yr, a 68% decline (P = 0.0007). In cultured retinal pigment epithelium, when we lowered the zinc concentration in the medium, metallothionein was reduced by 72% after 1 wk of incubation. CONCLUSIONS It is suggested that lower levels of metallothionein in retinal pigment epithelium are caused by reduced metallothionein gene activity or a faster rate of protein degradation, both of which are known to be regulated, at least partly, by bioavailable zinc.