Study On The Phenotype And Function Of B Cells In Glaucoma

Background:Glaucoma is a group of retinal neurodegenerative diseases that can cause irreversible visual impairment.The pathogenesis of glaucoma is complex and unknown,and the control of intraocular pressure is the mainstream treatment at present,but it can not reverse the damage of glaucoma to vision.Therefore,there is an urgent need to explore the pathogenesis of glaucoma more deeply.Existing studies have shown that immune response is involved in the process of glaucoma neurodegeneration,in which autoantibodies play an important role in the pathogenesis of glaucoma,but the research on antibody-secreting B cells in glaucoma is very limited.Objective:The purpose of this study was to investigate whether there are changes in the phenotype and function of B cells in glaucoma,explore the potential mechanism of B cells in the pathogenesis of glaucoma,and provide new ideas for the diagnosis and treatment of glaucoma in the future.Methods:A total of 44 glaucoma patients 38 with primary angle-closure glaucoma(PACG)and 6 with primary open-angle glaucoma(POAG)and 36 age-matched healthy donors(HD)were enrolled in the clinical study,and fresh peripheral blood was collected.Peripheral blood mononuclear cells(PBMC)were obtained by density gradient centrifugation,and B cells were analyzed by flow cytometry.The severity of glaucoma was determined based on the mean deviation(MD)value of visual field examination results.In animal experiment,the mouse model of glaucoma induced by Microbead was established,and the retina of the model was analyzed by immunofluorescence and flow cytometry.Results:In clinical studies,it was found that the total number of B cells increased significantly in patients with glaucoma.Further analysis of the changes of different B cell subsets in glaucoma showed that antibody secreting cells(ASC)/plasmablasts,na(?)ve and CD19~+CD27~-IgD~-double negative(DN)B cells increased,while CD27~+IgD~+unswitched memory B cells decreased.It was also found that the number of double negative B cells increased with the aggravation of clinical severity.In animal experiments,this study found nerve injury in the model retina and abnormal B cell infiltration in the diseased retina.Conclusion:This study confirmed the changes of peripheral B cell subsets in glaucoma for the first time,and revealed the correlation between a new proinflammatory subsets(CD27~-IgD~-DN)and the clinical severity of the disease,suggesting that this subsets may be used as a potential biomarker to monitor the disease progression of glaucoma patients.Abnormal B cell infiltration was found in the retina of glaucoma animal model,suggesting that B cells may be involved in the process of glaucoma nerve injury.