Proteomic Analysis Of Aqueous Humor Proteins In Patients With Primary Acute Angle-closure Glaucoma

Objective:Glaucoma is the second leading cause of blindness in the world.In China,primary acute angle closure glaucoma(PAACG)is the most common type of primary glaucoma.At present,the pathophysiological mechanism of glaucoma has not been clarified,and some patients still have complete loss of vision due to an acute attack in clinical practice.In recent years,studies have shown that some proteins in aqueous humor(AH)are involved in the pathogenesis of glaucoma,and pathological intraocular pressure elevation,as the primary risk factor for the pathogenesis of acute angle closure glaucoma(AACG),accelerates the progression of the disease.Through the proteomic detection of proteins in the aqueous humor of patients with acute closed glaucoma with different intraocular pressure,we explored the possible effect of differential protein expression in the aqueous humor of patients with acute closed glaucoma with different intraocular pressure on the pathogenesis of glaucoma,sought the possible mechanism of glaucomatous optic nerve injury,and provided experimental basis for studying the possible target of glaucomatous optic nerve protection.Methods:Eighty-eight selected samples were divided into two groups according to the intraocular pressure(IOP)of patients with PAACG: group A(36 samples,IOP≥50mm Hg)and group B(52 samples,IOP≤21mm Hg).Above samples were randomly divided into two cohorts,discovery cohort(group A,26 samples;group B,37 samples)and validation cohort(group A,10 samples;group B,15 samples),whose AH proteome were analyzed by data-independent acquisition method and by parallel reaction monitor method respectively.Results:In this study,a total of 636 proteins were detected from 63 aqueous humor samples in groups A and B of discovery queue,and 506 proteins were obtained for subsequent analysis after removing the default protein,of which 51 proteins were differentially expressed between the two groups.Among these 51 differential proteins,17 proteins were up-regulated in group A and 34 proteins were up-regulated in group B.The expression of differential proteins is associated with the remodeling of extracellular matrix(ECM)in trabecular meshwork(TM),inflammatory response,neurodegenerative diseases and lipid metabolic diseases,and involves the downregulation of some neuroprotective proteins.Among the above51 differential proteins,APOA2,TIMP1,LRP2 and VASN were randomly selected for PRM validation,and the study results showed that the results in the discovery queue were consistent with those in the validation queue.Conclusion:In our study,the protein in the aqueous humor of patients with primary acute closed glaucoma with different intraocular pressure was detected and analyzed.By searching the relevant literatures,explored the relationship between differentially expressed proteins and the pathogenesis and development of primary acute closed glaucoma under ocular hypertension,and it found that the expression of differentially expressed proteins was associated with inflammatory response as well as extracellular matrix remodeling in trabecular meshwork and nerve injury.The above factors may be an important cause of increased intraocular pressure and optic nerve injury in glaucoma.This study provides an experimental basis for in-depth understanding of the mechanism of glaucoma pathological injury and future drug development.