Impared ER stress caused by deficiency of thyroid hormone receptor

应激可促进RGC细胞死亡并抑制神经突起的延长，而视网膜胶质细胞在NMDA、NO或缺氧等应激下可促进RGC的存活。为了探讨应激诱导RGC死亡的机制，采用视网膜神经胶质细胞DNA微阵列技术。基因芯片结果显示，应激状态下甲状腺激素受体（TR）表达显著上调。为了研究TR与RGC存活的关系，用针对TR的siRNA转染RGC，抑制内源性TR的表达。与TR共同培养的RGC的存活率明显低于对照组，但与TR共同培养的RGC的存活率明显低于对照组。用siRNA敲除TR增强了视网膜胶质细胞中ATF 4的表达。这些结果提示内源性TR可能通过调节ATF4的表达，调节RGC的凋亡。

The stress enhanced the cell death of RGC and inhibited the prolongation of neurite, and retinal glial cells improve RGC survival under the stress like NMDA, NO or hypoxia. To explore the mechanisms of stress-induced RGC death, DNA microarray of retinal glial cells was used. DNA microarray indicated that thyroid hormone receptor (TR) is significantly upregulated in under the stress. To investigate the association between TR and the survival of RGC, theexpression of endogenous TR was inhibited by transfection with siRNA against TR. The survival rate of RGC cultured with TR supressed retinal glial cells, degreased. Knockout of TR with si RNA enhanced the expression of ATF4 in retinal glial cells. These results indicate that endogenous TR may have an important role for the expression of ATF4 and regulate the apoptosis in RGC.