Toxi city Study of Intrav it real Interfe ron-alpha in Rabbits

ABSTRACT

Interferon-alpha is known to inhibit the vascular endothelial cell proliferation and migration in vitro.It has been used systemically for the treatment of choroidal neovascular membrane proliferation.However, significant side effects in systemic administration limit the dosage and duration of its use. It has been suggested that reducing systemic side effects and maintenance of high intraocular concentration would be achieved with the direct intravitreal injection of Interferon-alpha.Thus, this study was undertaken to estimate the toxicity and safe dose of Interferon-alpha when it is given intravitreally in rabbits. Normal saline, Interferon-alpha 50, 000IU, 100, 000IU, 200, 000IU and 300, 000 IU were given intravitreally to 10 rabbit eyes.Toxicity was assessed by serial ERGs after 7 and 14 days.Animals were sacrificed at 14 days after injection for histopathologic study. The ERG was flattened at 14 days in 300, 000IU of Interferon-alpha group.On histologic examination, inflammatory reaction of vitreous and retina remained at an insignificant level upto 200, 000IU, but increased in dose dependent manner above this dose, resulting in prominent reaction in 300, 000IU group. Therefore, we suggest that 200, 000IU of Interferon-alpha may be the safe dose when administered intravitreally in rabbits, and 300, 000IU may be the toxic dose.