| Objective:The aim of this study is to establish a chronic intraocular hypertension model in rats by injecting hypertonic sodium chloride solution into superior scleral vein.To detect the changes in the expression of acetylcholinesterase in the retina of rats with chronic ocular hypertension.To observe whether bis(7)-tacrine has a protective effect on the changes in the number of retinal ganglion cells(RGCs)and the thickness of the retinal nerve fiber layer(RNFL)caused by the chronic ocular hypertension model in rats.Methods:1.Twenty-four adult healthy male Sprague-Dawley rats were randomly divided into 4 groups,namely: control group,1week high intraocular pressure group(1-week group),3 week high intraocular pressure group(3-week group)and 5 week high intraocular pressure group(5-week group).The basal intraocular pressure of all rats was measured before operation.No treatment was given to the eyes of the control group.The rats in the other 3 groups were injected with 50μL of 1.75mol/L hypertonic sodium chloride solution in the superior scleral vein of both eyes,only once.The intraocular pressure was measured on the first day after the model was made and every other day thereafter.The rat eyes were removed and the retina was prepared to prepare a tissue homogenate,and the activity of retinal acetylcholinesterase was detected by spectrophotometer colorimetry.2.Twenty-four adult healthy male Sprague-Dawley rats were randomly divided into 4 groups,namely: control group,operation group,bis(7)-tacrine group and memantine group.The basal intraocular pressure of all rats was measured before operation.The rats in the operation group,bis(7)-tacrine group and memantine group were injected with 50μL of 1.75mol/L hypertonic sodium chloride solution in the upper scleral vein of the right eye,and injected only once.The right eye of the control group was given the upper scleral vein puncture.The intraocular pressure is measured every three days and continuously monitored for one month.After the model was made,according to the body weight of the rats in the bis(7)-tacrine group and the memantine group,0.5 mg/kg bis(7)-tacrine and 5 mg/kg memantine were added to the drinking water of the two groups of rats every day.The operation group and the control group were given normal drinking water.All rats were sacrificed 5 weeks later,the right eye was removed and the retina was taken to prepare frozen sections,and immunofluorescence staining was used to detect the changes in the number of RGCs and the thickness of RNFL in rats.Results:1.The average binocular intraocular pressures of the1-week,3-week and 5-week groups were all higher than before 3days after modeling(P<0.05)and higher than 28 mm Hg,so the model can be considered as successful.The model of chronic ocular hypertension was successfully made.ACh E is expressed in the retina of all rats.The viability of ACh E in the retina of rats in the control group,1 week group,3 week group and 5 week group increased gradually with the increase of intraocular pressure from the time node of 0 day,7 day,21 day,and 35 day.The ACh E activity of the 1-week,3-week and 5-week groups was significantly different from that of the control group(all P<0.05).The Pearson correlation coefficient between the mean binocular intraocular pressure before sacrifice and the corresponding mean ACh E activity of rats in each group was r=0.951,P<0.05(bilateral),and the two were correlated.2.The average intraocular pressure of the right eye of the rats in the operation group,bis(7)-tacrine group and memantine group was higher than 28 mm Hg after 3 days of self-modeling,and they were all higher than the left eye(20.34±0.31 mm Hg)by more than 5mm Hg,which can be considered that the model was made successfully.The results of immunofluorescence staining showed that the number of RGCs passing through the optic nerve in the right eye of the rats in the control group,the operation group,the bis(7)-tacrine group and the memantine group was significantly different(F=24.31,P<0.05),and the number of RGCs in the operation group Significantly less than the control group,the difference was statistically significant(P=0.001<0.05).The number of RGCs in the bis(7)-tacrine group and the memantine group was less than that of the control group,but the bis(7)-tacrine group and the memantine group were compared with the control group respectively.The differences were not statistically significant(P=0.106/0.054).There was a statistically significant difference in the thickness of RNFL 200μm from the optic nerve in the right eye of rats in the control group,operation group,bis(7)-tacrine group and memantine group(F=80.527,P<0.05).The thickness of RNFL in the operation group and memantine group were both significantly lower than the control group.The difference between the operation group and the memantine group and the control group was statistically significant(P<0.05).The RNFL thickness of the bis(7)-tacrine group was slightly thinner than that of the control group,and the difference was not statistically significant(P =0.063).Conclusion:1.Acetylcholinesterase is expressed in the retina of rats with normal and chronic ocular hypertension.Within 5 weeks,the activity of ACh E in the retina of rats with chronic ocular hypertension has a positive correlation with the elevated level of intraocular pressure.2.Bis(7)-tacrine has a protective effect on the optic nerve by inhibiting the decrease in the number of RGCs and the thinning of RNFL in rats with chronic ocular hypertension. |
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