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J. Ahn, Y. Hong, G. Seong, H.–M. Lew, Y. Chang, S. Moon, I. Mook–Jung; Neuroprotective Effect of –2 Adrenoreceptor Agonist Against ER–stress Induced Apoptosis in Rat Retinal Ganglion Cell Line . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1311.
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Purpose: The objective of this study is to ascertain whether brimonidine protects retinal ganglion cells from ER stress in vitro, and if so, to determine the mechanisms of the neuroprotective effects of the brimonidine in cultured transformed rat retinal ganglion cell lines (RGC–5 cells). Methods: ER stress was induced by thapsigargin in cultured RGC–5 cells. A series of brimonidine, betaxolol or vehicle solutions were administered to the RGC–5 cells 1 hour before the administration of thapsigargin for 24 hours. The rate and the type of RGC–5 cell death were evaluated using LDH assay and TUNEL staining. The western blot analysis to caspase 3, caspase 12, and PARP was performed in thapsigargin treated RGC–5 cells in the presence or absence of brimonidine or a specific caspase 3 inhibitor. Results: The thapsigargin–induced death of RGC–5 cells was significantly inhibited by brimonidine but not by betaxolol. Thapsigargin increased the number of TUNEL(+) cells, which was inhibited by brimonidine but not by betaxolol. The western blot analysis confirmed that thapsigargin promoted cleavage of caspase 3, caspase 12 and PARP. The analysis also confirmed that brimonidine could inhibit the thapsigargin–induced activation of caspase 12 and caspase 3 in RGC–5 cells. The thapsigargin–induced cleavage of caspase 12 in RGC–5 cells occurred even if the activation of caspase 3 was blocked by a specific caspase 3 inhibitor. Conclusions: ER stress induced by thapsigargin caused the apoptosis of RGC–5 cells, and the thapsigargin–induced apoptosis of RGC–5 cells was blocked by brimonidine. The activation of caspase 12 and caspase 3 may contribute to the thapsigargin–induced apoptosis in RGC–5 cells. The activation of caspase 12 was thought to be uninfluenced by the activation of caspase 3. Brimonidine can inhibit the activation of caspase 12 and caspase 3 in the thapsigargin–treated RGC–5 cells, which may participate in the mechanisms involved in the neuroprotective effects of brimonidine in ER stress–induced apoptosis in retinal ganglion cells.
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