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Shoji Notomi, Toshio Hisatomi, Atsunobu Takeda, Yasuhiro Ikeda, Hiroshi Enaida, Tatsuro Ishibashi, Sr.; Involovement of P2X7 receptor and therapeutic efficacy of Brilliant Blue G in a mouse model of subretinal hemorrhage. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6540.
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We previously reported that Brilliant Blue G (BBG) is not only a useful aduvant in vitreo-retinal surgery but also a potential neuroprotective agent as a selective antagonist of P2X7 receptor in the retina. To investigate the involvement of P2X7 receptor in retinal diseases, we measured concentrations of P2X7 receptor agonist, extracellular adenosine triphosphate (ATP), in human vitreous samples. We also examined the therapeutic efficacy of BBG in a mouse model of subretinal hemorrhage.
We examined extracellular ATP levels of human vitreous samples collected during pars plana vitrectomy for patients including macular hole (MH), epiretinal membrane (ERM), and vitreous hemorrhage (VH). In vitro, ATP was added to primary retinal cell cultures from C57BL6 mice and the photoreceptor viability was assessed by calcein AM and CMTMRos. In vivo, we performed subretinal injection of autologous blood in C57BL6 mice in the absence or presence of BBG-treatment. Retinal cell apoptosis was evaluated by TUNEL method in cryosectionized specimens.
ATP concentrations in vitreous samples of VH were significantly higher than those of MH or ERM. In primary retinal cell cultures, incubation of ATP decreases photoreceptor cell viability and BBG-treatment attenuated photoreceptor death. Furthermore, BBG-treatment reduced TUNEL-positive apoptosis in a mouse model of subretinal hemorrhage.
P2X7 receptor activation by excessive extracellular ATP may be involved in pathogenesis of retinal diseases with massive hemorrhage. BBG provides a potential neuroprotective effect in subretinal hemorrhage.
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