METALLOTHIONEIN SHOWS AN AGE-RELATED DECREASE IN HUMAN MACULAR RETINAL-PIGMENT EPITHELIUM

Purpose. To investigate the possible role of zinc-metallothionein in h uman retinal pigment epithelium with regard to age-related changes. Me thods. 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 si gnificantly more metallothionein and zinc than macular retinal pigment epithelium. Macular retinal pigment epithelium cells contained 17.6 /- 2.2 mug 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 incubatio n. Conclusions. It is suggested that lower levels of metallothionein i n retinal pigment epithelium are caused by reduced metallothionein gen e activity or a faster rate of protein degradation, both of which are known to be regulated, at least partly, by bioavailable zinc.