The Effect Of EPO Gene Expression In The Pathogenesis And Treatment Of AMD

Purpose: To detect the effect of EPO on the occurrence and development of dry AMD and CNV in wet AMD;to detect the levels of cytokines in eyes with glaucoma and discuss the role of inflammatory mechanism in the occurrence and development of glaucoma.Method: 1)Construct AAV expression vectors,which carry the microRNA to inhibit EPO signal or,conversely,carry a non-erythrogenic variant of the EPO gene to enhance EPO signal.Meanwhile,establish conditional SOD2 knockdown mice model and CNV mice model,then an AAV vector will be subretinally injection to infect the RPE layer,then check the function and structure of retina to see the effect of EPO in dry AMD and CNV;2)detect the level of some cytokines in aqueous humor(AH)of patients with glaucoma by cytometric bead assay system and estimate the effect of inflammatory reaction in the pathogenesis of glaucoma.Results: 1)There was no abnormal damage in retina which injected with scAAV1-VMD2-EPOR76E;while there were damage like drusen in retina which injected with scAAV1-VMD2-EPO-miRNA and saline;2)The results of ERG shows that sub retinal injected with scAAV1-VMD2-EPOR76 E could protect retina while sub retinal injected with scAAV1-VMD2-EPO-miRNA could damage retina;3)subretinal injected with scAAV1-VMD2-EPO-miRNA could inhibit the development of CNV;4)Levels of TNF-?;IP-10;MCP-1;IL-2;IL-10 in eyes with glaucoma were higher than control eyes;while the level of IFNg had a positive correlation with age and the levels of IP-10;IL-2 and IL-5 in eyes of female patients with glaucoma were higher than male patients with glaucoma;the level of most of the measured cytokines had positive correlation with each other.Conclusion:1)EPO could protect retina in dry AMD;2)Lower EPO signal could inhibit the development of CNV;3)inflammatory and immune response involved in the occurrence and development of glaucoma.