Study On Phenotype And Function Of T Cells In Glaucoma

Background:Glaucoma is one of the most common causes of blindness in the world.Glaucoma is a complex neurological disorder characterized by irreversible damage to the Retinal ganglion cell nerve(RGC)and optic nerve(ON).The pathogenesis of glaucoma is very complex,and there is still no recognized mechanism that can completely explain the cause of glaucoma.Current theories cannot fully explain the pathogenesis of glaucoma,so in addition to the increase in intraocular pressure,what other key factors will determine the survival of retinal RGCs is urgent to solve.It has been proved that T cells play an important role in the injury of RGCs,but the mechanism of RGCs induced retinopathy is not clear.Purpose:The main objectives of this study are to determine the changes of different states of T cells in the pathogenesis of glaucoma,the differentiation of different subsets of T cells,and the influence of T cells on retinal damage in glaucoma.Methods:A mouse model of glaucoma with high intraocular pressure(IOP)was constructed,and the main functional effects,memory and Naive subsets of T cells in peripheral blood and spleen were detected for abnormal activation.Then,the infiltration of T cells in the center of glaucoma mice was studied to determine the changes in T cell number,infiltration and injury.Finally,the CD4 blockade experiment was chosen to investigate whether the RGCs injury was attenuated in glaucoma mice after blocked,to prove that aberrant activation of peripheral CD4~+T cells was associated with RGCs injury.Result:In this study,the MB mouse model was successfully established,and the proportion of effector subsets was increased in the periphery of MB mice.Flow cytometry analysis of the proportion of T cells in spleen and peripheral blood showed that the expression of CD44 was increased and the expression of CD62L was decreased.The increased proportion of Effector memory T cells(Tem,CD44+,CD62L-)and Central memory T cells(Tcm,CD44-,CD62L+)in the peripheral circulation of glaucoma patients was identified.The abnormal activation of T cells in glaucoma mice was confirmed.A robust retinal flow assay was then established.MB mice showed increased number of foreign lymphocytes,increased glial activation,increased expression of both major T cell subsets,CD4~+and CD8~+T cells,and abnormal CD4infiltration in the retina.Subsequently,CD4 blockade experiment showed that the damage of retinal RGCs was reduced after peripheral CD4 antibody blockade.Conclusion:This study confirmed the abnormal activation of peripheral T cells in MB mice and confirmed that the abnormal activation of T cells in glaucoma mice is related to the abnormal infiltration of retinal T cells and RGCs injury,it provides a new idea for the study of glaucoma mechanism.