Effect of retinoic acid on proliferation and polyamine metabolism in cultured bovine retinal pigment epithelial cells

Reports regarding the effect of all-trans-retinoic acid (RA) on the cell gr owth of retinal pigment epithelial cells (RPE) have been contradictory. The aims of this study are to clarify the in vitro effect of RA on RPE cells a nd to examine polyamine metabolism after RA stimulation. A 4-day incubation of fetal-calf-serum (FCS)-stimulated RPE cells with 10 or 25 mu M RA signi ficantly increased both cell number and [H-3]thymidine incorporation. RPE c ells grown over an extended period for 8 days also increased in number and reached full confluency. However, if the incubation was further extended to 12 days, no further increase in cell number was detected. RA treatment of FCS-stimulated RPE cells shifted the peak of ornithine decarboxylase (ODC) activity from 16 to 4 h. S-adenosylmethionine decarboxylase (SAMDC) activit y and spermidine/spermine N-1-acetyltransferase (SAT) activity of RA-treate d RPE cells were significantly greater until 8 and 16 h after incubation, r espectively. The putrescine content was significantly increased in RA-treat ed RPE cells up until 24 h, while spermidine, spermine and N-1-acetylspermi dine contents were significantly increased until 16 h. Our findings suggest that RA treatment increases the intracellular polyamine concentration of R PE cells via activation of ODC, SAMDC and SAT and that this results in the promotion of RPE cell growth until the cells reach full confluency.