Expression of glucose-regulated protein in rat retina with acute high intraocular pressure and its significance / 中华实验眼科杂志

ABSTRACT

BackgroundThe progressive death of retinal ganglion cells (RGCs) is the primary pathological characteristics of visual defects in glaucomatous eye.Research showed that endoplasmic reticulum stress (ERS) is involved in this progression.Glucose-regulated protein 78 ( GRP78 ) is a special marker of ERS.To understand the change in expression of GRP78 in the retina under the pressure induced is very important for the protection of visual function.Objective The present study was to observe the expression of GRP78 in rat retina with acute high intraocular pressure (IOP) and investigate the possible effect of ERS in acute glaucoma damage. MethodsFiftysix Wistar rats were randomly assigned to normal control group,anterior chamber punctured group and 12 hours,1 day,3,7,14 days groups following acute IOP rising.The acute high IOP models were established in the right eyes of 4.0 Wistar rats by paracentesis of the anterior chamber and infusion of normal saline solution into the anterior chamber.The histopathology changes of the retina were examined by hemotoxylin and eosin staining.The expression of GRP78 protein and mRNA in the retina were detected by immunohistochemistry and real-time fluorescence quantitative PCR.ResultsThe retinal layers and cells were clear with normal alignement in the rats of the normal control group and the anterior chamber punctured group.The edema and thickening of retinas appeared in 12 hours after molding and peaked in 1 day after molding.Then the retina decreased in thickness and atrophied from 3 days through 14 days.The expression levels of GRP78 protein (A value) were 0.195±0.006 in the nounal rats and gradually increased from 12 hours through 3 days (0.268±0.017) following molding with the peak value at 1 day (0.499±0.039 ),showing significant differences in comparison with the normal control group (t =0.098,0.304,0.073,P＜0.05),and the reduction in expression at 7 and 14 days were not significantly different from the normal control group ( t =0.002,0.001,P＞0.05 ).The relative value of GRP78 mRNA ( 2△△C1 ) in the retina was 1.011 ±0.013 in the normal control group and gradually up-regulated from 12 hours through 3 days with the peak value at Iday (2.141±0.171 ) and then down-regulated from the third day onwards.A significant difference was seen in 2-△△C1value between the normal control group and 12 hours group,1 day group or 3 group ( t =0.525,1.130,0.409,P＜0.05 ).However,the 2-△△C1 values of GRP78 mRNA at 7 and 14 days was similar to that of the normal control group (t=0.020,0.004,P＞0.05).ConclusionsGRP78 participates in the process of RGCs damage following acute high IOP.The results suggest that interfering with ERS may be helpful for protecting the retina and optical nerve from pressure-induced damage.