Experimental Study On Acute High Altitude Retinopathy Mechanism

Objective: Morphological changes of retinal tissues,early apoptosis rates and expressions of caspase-3 and p53 in rats were observed,so as to explore the mechanism of acute high altitude retinopathy of rats under stimulated hypoxic conditions at high altitude of 5000 m.Methods: A total of 70 adult female wistar rats were randomly divided into control group and experiment group.The 10 rats in control group were fed in the indoor environment at an altitude of 1500m(the altitude of Lanzhou city,with partial pressure of oxygen being 17.6 k Pa).The 60 rats in experiment group were randomly divided into 6 groups,10 for each group and were respectively fed in experimental module(partial pressure of oxygen: 11.3k Pa)simulating high-altitude environment(at an altitude of 5000m)for 2h,6h,12 h,24h,48 h and 72 h.After rats in all groups were killed,hematoxylin-eosin staining was applied to all groups to observe the changes of pathological features of rats' retinas,while immunohistochemical staining was applied to observe the expressions of caspase-3 and p53,Image-Pro Plus image analystic software was used to calculate the average absorbance value(A)of positive cells and analyze the correlation between caspase-3 and p53 expressions,and flow cytometry was used to detect the early cell apoptosis rates.Results: 1.The results of pathological slices of all groups: Retinal tissues in control group were clear and complete in structure,even in thickness,clear in tissue structure of each layer;ganglion cells were in monolayer sequence,and the cell nucleuses were larger and elliptical in shape;the simulative high-altitude hypoxic conditions could induce tissue injury of rats' retinas,thus leading to the changes of pathological features of retinas.In experiment group,each layer tissue of rats' retinas had edema and looseness,and thickened retinal thickness with layer sequence disorder,indicating decrease of cell nucleuses and occurrence of vacuolar degeneration in ganglion cell layers,and the longer the anoxia time was,the more serious pathological injury of retinas would become.2.The expression results of caspase-3 and p53 in rats' retinas of each group: In control group,p53 and caspase-3 micro-expressed or did not express in ganglion cell layers in rat's retinas;in experiment group,caspase-3 and p53 expressions could be deteced after 2h,which increased gradually along with time,and there were significant differences(P<0.05).Spearman correlation analysis showed that caspase-3 and p53 expressions were positively associated with rat's retinal tissues(r=0.832,P<0.001).3.Detection results of early apoptotic rates of rats' retinal cells in all groups: The early apoptotic rate of cells was 0.46% in normal control group,which increased along with the time of anoxia,and was markedly elevated at 48 h in experiment group.There was insignificant difference between 2h group and control group,but it had significant differences in other groups(P<0.01).Conclusions: 1.The simulative high-altitude of 5000 m hypoxia conditions could induce tissue injury of rats' retinas,thus leading to the changes of pathological features of retinas.2.Cell apoptosis may participate in the retinal injury mechanism of rats with simulative high-altitude hypoxia and may play its role through caspase-3-depended apoptotic pathway.