ATLA::Alternatives to Laboratory Animals

Volume 27, Number 3

Retinal pigment epithelial cell cultures as a tool for evaluating retinal toxicity in vitro.

ATLA 27, 413-415, May/June 1999

Hanna Tähti,¹ Hanna Mäenpää,¹ Lotta Salminen² and Tarja Toimela¹

¹Medical School, University of Tampere, P.O. Box 607, 33100 Tampere, Finland; ²Tampere University Hospital, P.O. Box 2000, 33520 Tampere, Finland

SUMMARY

This article reviews in vitro testing of retinal toxicity in retinal pigment epithelium (RPE) cell cultures. It is based on the literature on RPE cell cultures and on our recent studies on the retinal toxicity of selected amphiphilic drugs. The RPE plays a major role in maintaining the homeostasis and health of the retina. Various pharmacological agents are known to cause adverse effects in RPE cells. For example, long-term treatment with chloroquine in patients with rheumatoid arthritis has induced retinopathy, and tamoxifen, a drug that is commonly used in the treatment of advanced breast cancer and in the prevention of breast cancer among high-risk women, has been reported to cause retinal changes and impaired vision. Dunng our research, we have developed novel in vitro methods for evaluating the retinal toxicity of xenobiotics. We have used a pig RPE primary culture and a human RPE cell line (D407), which retain epithelial cell characteristics. They form a layer of hexagonal cells with intercellular junctions, and possess a keratin-containing cytoskeleton. They are both good models for determining the retinal cell toxicity of test compounds. Further studies on phagocytic activity, Iysosomal enzyme activity and glutamate uptake might generate new methods for the toxicological evaluation of the retinal side-effects of drugs in vitro.

Keywords: retinal toxicity, retinal pigment epithelial cell cultures, phagocytic activity, glutamate uptake