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A. F. Thompson, C. J. Lieven, N. Sheibani, L. A. Levin; Radioprotective Effects of a Cell-Permeable Redox Agent on Retinal Endothelial Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1403.
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© ARVO (1962-2015); The Authors (2016-present)
Radiation retinopathy and radiation optic neuropathy are common adverse effects of radiation treatment of ocular tumors. One of the mechanisms for neuroretinal radiation damage is injury to endothelial cells (Levin LA et al., Ophthalmology 107:370, 2000), possibly mediated by generation of reactive oxygen species. We hypothesized that a phosphine-borane complex which we had previously shown to be neuroprotective of retinal ganglion cells following axotomy (Schlieve CR et al., Exp Eye Res 83:1252, 2006) would protect retinal endothelial cells from radiation damage.
Retinal endothelial cells (Su X et al., Mol Vis 9:171, 2003) were subjected to ionizing radiation from a 137Cs source, using single doses from 1 to 30 Gy. Experimental groups of cells were treated with bis(3-propionic acid methyl ester)phenylphosphine borane complex (PB1) at concentrations ranging from 100 pM to 100 uM 18 hours before, immediately preceding, or 18 hours after irradiation. Cell viability was assessed by staining live cells with calcein-AM 72 hours after irradiation. Cells were photographed and batch-analyzed using ImageJ.
Retinal endothelial cell viability was reduced to 56.1 ± 6.3% and 37.1 ± 3.5% of control following 10 and 30 Gy irradiation, respectively (p < 0.004 for both comparisons). Treatment with 10 nM or 100 nM PB1 18 hours before, immediately preceding, or 18 hours after 10 Gy irradiation significantly increased numbers of viable cells (p < 0.05). Treatment with 10 nM PB1 18 hours after 10 Gy irradiation showed the strongest protective effect (viable cells increased to 127.8 ± 20.3% of control, p = 0.005). Treatment with all PB1 concentrations tested between 100 pM and 100 µM at any of the three experimental time points significantly increased numbers of viable cells following 30 Gy irradiation (p < 0.05). 10 nM PB1 treatment immediately before irradiation was most protective against this highest 30 Gy radiation dose (viable cells increased to 101.1 ± 9.6% of control, p < 0.0001).
The redox modulating agent PB1 has a radioprotective (administration before radiation) and radiomitigative (administration after radiation) effect in irraditated retinal endothelial cells. The mechanism may relate to interruption of oxidative signaling pathways for apoptosis induced by radiation.
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