Retinal Safety Study of Intravitreal Genistein in a Rabbit Model

Abstract

Purpose: : To evaluate the preclinical safety of intravitreal genistein in rabbit eyes over a short-term period.

Methods: : Twelve New Zealand albino rabbits were selected for this study. Four concentrations of genistein were prepared: 24 mg/0.1 mL, 135 mg/0.1 mL, 270 mg/0.1 mL and 540 mg/0.1 mL. Each concentration was injected intravitreally in one eye of three rabbits. As a control, the vehicle solution was injected into the other eye of each animal. Retinal safety of intravitreal genistein was studied with electroretinography (ERG) and histopathology in rabbits. ERG recordings were made before the injection and 3 weeks after. Eventually, the rabbits were euthanatized and the retinas examined by light and electron microscopy. Immunohistochemical staining with caspase-3 and -9 was also performed to evaluate apoptotic expression in all study and control sections.

Results: : ERG studies showed no significant difference between control and genistein-injected eyes at any of the doses in the rabbit model. Histological examination revealed no retinal abnormality in the rabbits injected with each concentration of genistein. Immunohistochemical staining with caspase-3 and -9 showed no different apoptotic protein expression in all study and control sections.

Conclusions: : Our results indicate that genistein is a safe intravitreal drug in the rabbit model up to 540 mg. If proven safe and efficacious in further studies, intravitreal injection of genistein could be considered an alternative therapy to that currently used in selected patients.

Keywords: injection • drug toxicity/drug effects • immunohistochemistry