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3/2016
vol. 118 abstract:
Original paper
The effect of intravitreal ranibizumab on apoptosis induction in rat retinal tissue
Anna Machalińska
1, 2
,
Ewa Pius-Sadowska
3
,
Michał Sekrecki
3
,
Miłosz P. Kawa
3
,
Dorota Rogińska
3
,
Bogusław Machaliński
3
Online publish date: 2017/11/29
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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 ir¬reversible 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. keywords:
apoptosis, ranibizumab, retinal degeneration, vascular endothelial growth factor |
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