Effects of 3,3'-iminodipropionitrile on the peripheral structures of the rat visual system

Adult male Long-Evans rats received 3,3'-iminodipropionitrile (IDPN; 400 mg/kg i.p.) and were killed one day after one dose, or one, three, seven, thirty-five, or seventy day(s) following 3 consecutive daily doses for histological analysis of the eye. Histological alterations in visual structures were not observed before one day after the third dose of IDPN. Somato-dendritic swelling of cells in the inner nuclear (IN) layer was seen prior to retinal detachment (1 day after cessation of dosing) followed by progressive retinal degeneration (35 and 70 days). IDPN exposure resulted in opacification of the cornea and vascular hemorrhaging into the subretinal space (3 days) followed by complete detachment of the retina (7 days). The corneal opacification was transient and resolved by 14 days post-treatment. The retina underwent complete spontaneous reattachment between 35 and 70 days after IDPN administration. A subsequent experiment was performed to characterize the dose-response of IDPN on retinal histology, 2 weeks after the last dose (0, 100, 200, 400 mg/kg x 3 days). In the dose-response experiment, retinal detachment and degeneration in the IN layer were only apparent in the 400 mg/kg dose group. However, increased GFAP immunoreactivity in the retina was observed in the 200 mg/kg dose group without overt retinal pathology. Results indicate that the corneal opacification, vascular hemorrhaging, and detached retinae recovered in a time-dependant manner, while neurodegeneration of the visual retina was progressive, even after the retina had reattached. The present study indicates that this toxicant may have direct effects on both neural and non-neural structures, and characterizes the time-course and dose-response of histopathological changes in the retina.