Purchase this article with an account.
Ikram El-Zaoui, Francine F Behar-Cohen, Alicia Torriglia; Glucocorticoids exert direct toxicity on microvasculature by triggering cell death of endothelial cells. Invest. Ophthalmol. Vis. Sci. 2014;55(13):4895.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Glucocorticosteroids (GCs) are widely used in the treatment of many pathologies, including ophthalmological diseases. Notably, high doses of GC are injected intra-ocularly or systemically to treat macular oedema, neovascularization and numerous general inflammatory states. Amongst the widely recognized side effects of GCs, microvascular injuries have been reported. However, the underlying mechansims of GC toxicity on microvasculature have not been explored so far. The purpose of our study was therefore to explore the toxic effects of the GCs on endothelial cells.
To achieve this goal, we used three different models: the cells of the human microcirculation (HMEC), bovine retinal endothelial cells (BREC) and ex-vivo analysis of the mounted rat retinas. We tested four GCs: Hydrocortisone, Dexamethasone, Dexamethasone phosphate and Triamcinolone Acetonide. In the preliminary experiments, we first ascertained that all three models are GC targets by verifying by Q-PCR the expression of gluco- and minralo- corticoid receptors. The efficiency of each GC was next estimated by determining their LD50 by using MTT test. Mechanisms of cells death were explored by quantification of lactate dehydrogenase release, DNA fragmentation, immunohistochemistry and western blot.
We found that GCs trigger a decrease of cell viability. The effect of GC was dependent on both chemical structure of GC and cell type. The most hydrophobic GCs are though the most toxic. The endothelial cells of the general microcirculation are more sensitive than the retinal endothelial cells. The study of the relevant mechanisms of cell death pointed to the activation of both caspase -dependent and independent pathways (AIF and LEI/L-DNaseII). These in vitro results were confirmed on the ex-vivo model.
Overall, our data show that the therapeutically used doses of GCs are toxic for endothelial cells. This should be taken into the consideration in the clinical use of these compounds
This PDF is available to Subscribers Only