The Effect Of AQP4Gene On The Activation Of Retinal Glial Cells In Chronic High Intraocular Pressure Mice

Objective To investigate whether aquaporin4(AQP4) gene can affect the activationof glial cells and cause the injury of retina of chronic high intraocular pressure micemodels,and to discuss its possible mechanism.Methods The chronic high intraocular pressure models were established by burningthe scleral venous of the right eye, which as the experiment group, and the left eyewithout any treatment as the control group. The intraocular pressure (IOP) wasmeasured by icare rebound tonometer. Selected each of the successful model ofchronic high intraocular pressure male AQP4knockout mice(AQP-/-) and theirwild-type(WT) male mice40, divided the two type of mice into five groups afterscleral venous burn according to the time of establishing models(24h,3d,1w,2w,4wafter scleral venous burn),8mouse of each group. And then producing the paraffinsections of mouse eye. Immunohistochemical staining methods was used to observethe expression of the glial fibrillary acid protein(GFAP) in retina glial cells, andobserve the expression of the AQP4in the retina of the WT mouse. HE stainingmethods was used to detect changes of the retinal thickness. Image acquisition underthe fluorescence microscopy. The intraocular pressure was analyzed by t-test,ANOVA and SNK methods.Results After scleral venous burn (24h,3d,1w,2w,4w), there was a significant difference(P<0.05) in the IOP of the two types of mice between the experimental andcontrol groups.HE staining showed that after3days of the high intraocular pressurethe two types of mice retina begins thickening, after1week the retina obviousthinkening and the retinal ganglion cell edema, cytoplasm become bright and empty,inner retina cell gap increases, after2weeks still thicker than the control group.After4weeks of the high IOP the retina gradually shrinking, and can be seen part of theganglion cell nuclei smaller and deeply stained. Since24hours after the scleralvenous burn,the expression of GAFP of the two type mice began to increase andreached to peak at1week after burning. This peak of WT mice was more obviousthan that of AQP4-/-mice. The concentration of GAFP began to decrease at2weekslater afere burning and reached to bottom at4weeks later. To the WT mice, theexpression of AQP4was remarkable higher in experimental group than that in controlgroup at1week after the scleral venous burn. The expression of AQP4is related tothe expression of GAFP in high intraocular pressure of WT mice at1week,2weeks,and4weeks after the scleral venous burn..Conclusion The chronic high intraocular pressure models can be establishedsuccessfully by burning the scleral venous. AQP4gene can affect the activation of theglial cells in chronic high intraocular pressure mice and lead to the injury of retina,which may be a new target to treatment of glaucoma.