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Shoji Notomi, Toshio Hisatomi, Atsunobu Takeda, Yasuhiro Ikeda, Hiroshi Enaida, Tatsuro Ishibashi; Neuroprotective Effect Of Brilliant Blue G As A Selective P2x7 Receptor Antagonist In Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5449.
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Recently we have demonstrated Brilliant Blue G (BBG) has excellent staining ability and biocompatibility as an adjuvunt for cataract and vitreous surgery. BBG is also known as a selective P2X7 receptor antagonist. P2X7 receptor is a subtype of P2X receptors, which are extracellular ATP sensitive cation channels. ATP is released into extracellular space and implicated in neuronal cell death in several animal model of neurodegenerative diseases. We investigated the involvement of P2X7 receptor in retinal pathology and the neuroprotective effect of P2X7 receptor antagonism by BBG in retinal neurons.
We examined cytotoxcity and cell viability after co-incubation of ATP or more selective P2X7 agonist, 2'- and 3'-O-(4-benzoylbenzoyl)-ATP (BzATP) in mouse primary retinal culture. We also evaluated the effect of BBG for starved primary retinal cells by B27 supplement deprivation. Next, we investigated the toxicity of P2X7 stimulation in vivo, ATP and BzATP were intravitreally injected in C57BL6 mice and Apoptosis was detected by TUNEL method. The effect of co-injection of BBG is also tested.
In primary retinal culture, incubation of ATP or BzATP decreases photoreceptor cell viability and pre-incubation of BBG rescued photoreceptor cells. Furthermore BBG reduced the loss of cell viability after starvation. In vivo, 24 hours after injection of ATP or BzATP, TUNEL positive cells were detected in photoreceptor layer and co-injection of BBG prevented photoreceptor apoptosis.
P2X7 receptor agonist ATP and BzATP is toxic in retina and their toxicity is inhibited by BBG. BBG is a potential agent which has both staining ability in intraocular surgery and neuroprotective effect in retina.
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