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H. Oku, M. Fikuhara, T. Okuno, T. Kurimoto, T. Sugiyama, T. Ikeda; Endothelin-1 (ET-1) Is Increased in the Retina After Optic Nerve Injury. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5373. doi: https://doi.org/.
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Endothelin-1 (ET-1) is the most potent and long-acting vasoconstricting peptide ever known, which is also deeply related to cell death signaling pathway of retinal neurons. We evaluated alteration in the expression of ET-1 and its specific receptors in the sensory retina after optic nerve injury.
Optic nerve crush or sham operation was performed in the right eye of rats. Sensory retinas were excised 1, 2, 4, 7 and 14 days after the operation, and the amount of ET-1 in the retinas was measured by radioimmunoassay (RIA) and mRNA levels of the specific receptors were determined by RT-PCR. Alteration of these expressions was also investigated using immunohistochemical methods.
The ET-1 levels in the sensory retinas with optic nerve crush were 8.83 ±2.23 (mean ±SD, n=6) and 9.99 ± 4.83 pg/mg. protein (n=5) on day 7 and 14 after the injury, while those of sham control were 4.55 ±1.36 (n=6) and 4.85 ±1.57 pg/mg. protein (n=5), respectively. These increases were significant (P<0.05, Kruskal-Wallis followed by Mann-Whitney U test). The mRNA levels of ETA and ETB receptors in the retina after optic nerve crush were increased to 136.1 ± 16.3 (P=0.08) and 172.3 ±15.0 % (P=0.02, n=4, Mann-Whitney U test) to those from sham controls on day 7. Immunohistochemical analyses revealed ET-1 expression was increased mainly in the internal retina including nerve fiber layer and ganglion cell layer (GCL). Increased immunoreactivity to ETB receptor was seen in the GCL cells and, also interestingly, in the outer nuclear layer.
ET-1 signaling pathways are activated in the sensory retina after optic nerve crush, which may closely be related to the retinal remodeling and survival for some kinds of retinal neurons after optic nerve injury.
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