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Masayoshi Yukita, Shigeki Machida, Kazuko Omodaka, Kazuichi Maruyama, Toru Nakazawa; Brimonidine Enhances Electrophysiological Activity of Retinal Ganglion Cells through Trk-PI3K Pathway. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6199.
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© ARVO (1962-2015); The Authors (2016-present)
It has been reported that an intravitreal injection of brimonidine elevates BDNF level in the retinal ganglion cell (RGC) layer and protects RGCs from cell death in rats. However, electrophysiological change of RGCs induced by the intravitreal brimonidine remains unknown. In this study, we investigate the changes of RGC activity by measuring the positive scotopic threshold response (pSTR) of the electroretinogram (ERG) in eyes injected with brimonidine.
We used 40 adult Sprague-Dawley rats. The right eyes were injected with DPBS (1μl) as control, and the contralateral left eyes were injected with brimonidine (0.10nmol). Scotopic ERGs were recorded simultaneously from both eyes at 1, 2, 3, 7 and 10 days after the intravitreal injection. Amplitudes of the a- and b-waves and the pSTR were measured. In other experiments to elucidate the mechanism of the ERG changes induced by intravitreal brimonidine, we injected K252a (an inhibitor of tyrosine kinase phosphorylation of Trk receptor: 0.06 pmol), U0126 (MAPK/ERK kinase inhibitor: 0.15 nmol) or LY294002 (phosphoinositide 3-kinases(PI3Ks): 0.60 nmol) with brimonidine into the left eyes and recorded ERGs with a same protocol. One-way repeated measures ANOVA was used to determine statistical significance.
In the brimonidine-injected eyes, the pSTR amplitudes were significantly increased to 133.5±27.4%, 147.1±21.2% and 130.2±19.4% (5 animals at each time point, P<0.01) as compared to those of the control eyes at the day 1, 2 and 3 after the injection, respectively. However, the enhanced amplitudes of the pSTR returned to the normal level (109.0±21.7%) at the day 7. The intravitreal injections of K252a or LY294002 significantly reduced the enhancement of the pSTR induced by the intravitreal brimonidine (P<0.01). In contrast, the U0126 injection did not affect the enhancement of the pSTR.
The intravitreal brimonidine enhanced electrophysiological activity of RGCs in rats. Activation via Trk receptor and PI3K signals were involved in the mechanism of the electrophysiological change. It would be interesting to investigate an association between this neuroactivation and neuroprotection of brimonidine in the future.
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