Retinal damage induced by cisplatin in neonatal rats and mice

Purpose. The morphologic response of the retina at different neonatal ages to various doses of cis-platinum(II) diamminedichloride (cisplatin) was exa mined in rats and mice. Methods. Cisplatin was given to rats at a dose of 1, 3 or 5 mg/kg at 0 days or 5 mg/kg at 7 or 14 days of age, and to mice at 0.5, 1.5, 3 or 6 mg/kg a t 0 days or 6 mg/kg at 7 or 14 days of age, and the animals examined 12 and 24 hrs, and 3 and 7 days after the treatment. Results. In both species, regardless of gender, with greater than or equal to 3 mg/kg cisplatin treatment (lethal dose) at day 0, retinal damage chara cterized by the appearance of aggregations of TUNEL-positive cells scattere d in the undifferentiated neuroblastic layer was seen at 24 hrs, and led to rosette formation at day 3 and 7 (retinal dysplasia). At the ultrastructur al level, neuroblastic cells showed condensation of chromatin and shrinkage of the cytoplasm, and rosettes encircled by an outer limiting membrane. Ce ll debris phagocytosed by pigment epithelial cells was seen. However, cispl atin at < 3 mg/kg in 0-day-old animals or at high dose in greater than or e qual to 7-day-old animals caused no damage to the retina. Conclusions. A critical period (day 0) for the administration and a thresho ld dose (greater than or equal to 3 mg/kg) of cisplatin in the development of retinal damage in rats and mice was seen. Although the cisplatin dose ne cessary to damage the retina caused a high incidence of mortality, it was b elow the human therapeutic dose.