Ocular lesions induced in infant rats by busulfan

Although busulfan, a bifunctional alkylating agent, is known to induce cataracts in infant rats, the full nature of busulfan-induced ocular lesions has not yet been shown. In order to clarify this point, 6-day-old rats were treated with a single dose of 20 mg/kg busulfan and the ocular tissue was histopathologically and immunohistochemically examined at 1, 2, 4, 7 and 12 days after treatment (DAT). As a result, in the nuclear layer (NL) of the peripheral retina, apoptotic cells significantly increased at 1 DAT and peaked at 2 DAT when cell proliferating activity was depressed. At 4 DAT, the NL showed wavy deformation with formation of rosette-like structures, and these changes progressed prominently at 12 DAT. In addition, a significant reduction in the retinal thickness due to decreased thickness of NL or inner NL was detected at 2 and 4 DAT. On the other hand, in the germinative zone of the lens equator, apoptotic lens epithelial cells significantly increased from 2 to 7 DAT, resulting in partial loss of lens epithelial cells at 7 and 12 DAT. At 12 DAT, prominent swelling and vacuolation of lens fibers were observed in the area from the equatorial zone to the posterior pole, indicating the development of cataract. The present results strongly suggest that prominent apoptosis in component cells was the initial and essential event underlying the development of busulfan-induced ocular lesions in infant rats.