Research on the Endoplasmic Reticulum Stress Mechanism of Apoptosis Induced by Ischemic Retinal Injury
Objective To analyze the effects of ischemia on the expression of endoplasmic reticulum stress(ERS)-related proteins glucose regulated protein78(GRP78),C/BEBP homologous protein(CHOP),and cysteinyl aspartate specific proteinase(Caspase)-12 during the apoptotic process of retinal ganglion cells(RGCs),and to investigate the molecular level pathogenesis of ischemic retinal injury(IRI)-induced RGCs apoptosis,to provide a new idea and method for the prevention and treatment of IRI.Methods The anterior chamber high intraocular pressure method was applied to produce a rat right eye IRI model.Forty healthy male SD rats were randomly divided into the normal control group,30-min IRI group,60-min IRI group,and 120-min IRI group according to the ischemic time,with 10 rats in each group.Hematoxylin-eosin(HE)staining was applied to observe the changes in retinal histomorphology in different groups of rats;immunohistochemical(IHC)staining was applied to observe the expression and localization of apoptosis-related factors such as B-cell lymphocyte/leukemia-2(Bcl-2),Bcl-2 associated X protein(Bax),and Caspase-3 in different groups;immunofluorescence(IF)staining was applied to observe the expression and localization of ERS-related proteins such as GRP78,CHOP and Caspase-12 in other groups.Results HE staining results showed that compared with the normal control group,retinal edema,increased thickness of the inner retinal layer,disturbed distribution of retinal cells,decreased number of RGCs,and increased vacuolar tissues were observed in the IRI groups.IHC staining results showed that only a small amount of Bax and Caspase-3 proteins were expressed in the retina of the normal control group,while Bax and Caspase-3 proteins were mainly expressed in the ganglion cell layer and the inner nuclear layer of the retina in the IRI groups.The expression of Bax and Caspase-3 proteins in the retina of the IRI groups was significantly higher than that of the normal control group,and the differences between the IRI groups were also statistically significant.A large amount of Bcl-2 protein was observed in the ganglion cell layer and inner nuclear layer of the retina in the normal control group.Compared to the normal control group,the expression of Bcl-2 protein in the retina of each IRI group was significantly reduced,and the differences between the IRI groups were also statistically significant.The results of IF staining showed that the positive expressions of GRP78,CHOP,and Caspase-12 in the retina of the normal control group were small,while their expressions in the ganglion cell layer and the inner nuclear layer in the retina of the IRI groups were significantly increased compared with the normal control group.Conclusions IRI can induce apoptosis in the retinal cells,and its mechanism may be related to the activation of ERS-related pathways.
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