Preclinical studies of ranibizumab for safe use in ophthalmology clinic

The research effort entertained herein aimed at evaluating the possible effects of cell injury by ranibizumab in biological assays, in order to prove its safety for use in humans. For this, indirect ophtalmoscopy in albino rabbits was evaluated in vivo for a period of 21 days following intravitreal administration of ranibizumab (10mg/mL) in volumes of 30 and 50µL, or 50µL of saline solution, and retinal histological staining of the rabbits’ eyes performed with hematoxylin/eosin. The assays involving ranibizumab were performed in vitro in cell cultures of murine fibroblasts, at concentrations of 2.5, 10, 250, 350 and 500µg/mL. Thorough histological analyses of the retinal tissue showed that intravitreal administration of ranibizumab caused neither cellular suffering or cell death in the in vivo assays, while in the in vitro assays it was only possible to determine the IC10. Therefore, the iatrogenic complications observed clinically after intravitreal administration of ranibizumab may be due to flaws in the administration procedure. Hence, both in vitro and in vivo assays show that the ranibizumab proved to be safe for the treatment of Age-Related Macular Degeneration, as the determination of IC10 has only been feasible within the concentrations used in the posterior segment of the human eye.