@Article{Machalińska2016,
journal="Klinika Oczna / Acta Ophthalmologica Polonica",
issn="0023-2157",
volume="118",
number="3",
year="2016",
title="The effect of intravitreal ranibizumab on apoptosis induction in rat retinal tissue",
abstract=" Purpose : Despite the rapidly accumulating knowledge on pharmacokinetic properties and dosage of ranibizumab, the influence of this vascular endothelial growth factor inhibitor on retinal cell survival/apoptosis homeostasis remains unclear. The aim of this study was to investigate the biological effects of a single intravitreal injection of ranibizumab on retinal tissue with a focus on apoptosis-related signaling pathways in the rat retina.  	 Material and methods : Male Wistar rats were treated with an intravitreal injection of ranibizumab or anti-rat vascular endothelial growth factor antibody in the right eye. The left eyes were injected with the same volume of physiological saline. On the 3rd and 7th day post-injection, the eyes were enucleated, and the retinas were isolated for further molecular analysis of the expression of selected apoptosis-related molecules at mRNA (BAX, BCL-2) and protein (caspase-3) levels using quantitative RT-PCR and western blot techniques, respectively.  	 Results : Following a 3-day-exposure to ranibizumab at the established concentration, the BAX/BCL-2 mRNA expression ratio was significantly increased compared to the saline-treated controls and the healthy control eyes. Furthermore, on day 3. post ranibizumab injection, caspase-3 cleavage, detected qualitatively using western blotting, confirmed potential activation of the ir­reversible phase of apoptosis. In contrast, on day 7. post-injection, there were no significant differences in the BAX/BCL-2 mRNA expression ratios or caspase-3 cleavage between different groups.  	 Conclusions : Intravitreal administration of ranibizumab leads to a transient induction of apoptosis in retinal cells, with an onset directly after the vascular endothelial growth factor inhibitor administration and apparent down-regulation shortly afterwards. These results must be considered when intravitreal injections of ranibizumab are administered to treat retinal diseases.",
author="Machalińska, Anna
and Pius-Sadowska, Ewa
and Sekrecki, Michał
and Kawa, Miłosz P.
and Rogińska, Dorota
and Machaliński, Bogusław",
pages="201--207",
doi="10.5114/ko.2016.71705",
url="http://dx.doi.org/10.5114/ko.2016.71705"
}