Toxicity and antiproliferative effect of aclacinomycin A on RPE cellsin vitro

Abstract

Aclacinomycin A or aclarubicin is an anthracycline that, by contrast with daunomycin, lacks carcinogenicity and is less toxic to the retina. We investigated the toxicity and antiproliferative effect of aclacinomycin A on retinal pigment epithelial cells that are known to play a mayor role in the pathogenesis of proliferative vitreoretinopathy. In 3 experimental set-ups, RPE cells from pig eyes were incubated with aclacinomycin A at different concentrations (0.5-15 micrograms/ml) and for various lengths of time (1-10 min). Cells were counted on day 3 after exposure to evaluate toxicity, subcultured, and counted once more on day 15 to test for the antiproliferative effect. Data were analyzed using the Tukey's Studentized Range (HSD) Test. Furthermore, RPE cells were examined by light microscopy. Cell numbers on day 3 after treatment were reduced significantly (p < or = 0.05) already at the lowest dosage tested (1 microgram/ml for 1 min). Higher doses, up to 15 micrograms/ml for 5 min, did not lower cell numbers below 20% of those of control cultures. Logarithms of cell numbers on day 15 were inversely correlated to drug concentration as well as to incubation time. Cells that had been treated with 5 micrograms/ml aclacinomycin A for 5 min were not able to start a new culture when subcultured 3 days after drug exposure. Aclacinomycin A applied intraocularly during vitreoretinal surgery may be an alternative to daunomycin in the treatment of proliferative vitreoretinopathy.