Retinal damage induced by cisplatin in neonatal rats and mice.
OBJECTIVE
The morphologic response of the retina at different neonatal ages to various doses of cis-platinum(II)diamminedichloride (cisplatin) was examined 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 at 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 > or = 3 mg/kg cisplatin treatment (lethal dose) at day 0, retinal damage characterized by the appearance of aggregations of TUNEL-positive cells scattered in the undifferentiated neuroblastic layer was seen at 24 hrs, and led to rosette formation at day 3 and 7 (retinal dysplasia). At the ultrastructural level, neuroblastic cells showed condensation of chromatin and shrinkage of the cytoplasm, and rosettes encircled by an outer limiting membrane. Cell debris phagocytosed by pigment epithelial cells was seen. However, cisplatin at < 3 mg/kg in 0-day-old animals or at high dose in > or = 7-day-old animals caused no damage to the retina.


CONCLUSIONS
A critical period (day 0) for the administration and a threshold dose (> or =3 mg/kg) of cisplatin in the development of retinal damage in rats and mice was seen. Although the cisplatin dose necessary to damage the retina caused a high incidence of mortality, it was below the human therapeutic dose.
Yang
J
J
Department of Pathology II, Kanasi Medical University, Moriguchi, Osaka 570-8560, Japan.
Yoshizawa
K
K
Shikata
N
N
Kiyozuka
Y
Y
Senzaki
H
H
Tsubura
A
A
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects* / Q000473:pathology*
D000970:Antineoplastic Agents; D002945:Cisplatin