Abstract
BackgroundWe reviewed the literature on the aqueous humor (AH) proteome of primary open angle glaucoma (POAG) patients in order to obtain deeper insight into the pathophysiology of POAG. MethodsWe searched Pubmed and Embase up to May 2019 for studies that compared AH protein composition between POAG (cases) and cataract (controls). Untargeted studies (measuring the whole proteome, by LC-MS/MS) were divided into two subgroups depending on the type of surgery during which POAG AH was collected: glaucoma filtration surgery (subgroup 1) or cataract surgery (subgroup 2). We reanalyzed the raw data (subgroup 1) or combined the reported data (subgroup 2) to perform GO enrichment (GOrilla) and pathway analysis (Pathvisio). ResultsOut of 93 eligible proteomic studies, seven were untargeted studies that identified 863 AH proteins. We observed 73 differentially expressed proteins in subgroup 1 and 87 differentially expressed proteins in subgroup 2. Both subgroups were characterized by activation of the acute immune response, dysregulation of folate metabolism and dysregulation of the selenium micronutrient network. For subgroup 1 but not for subgroup 2, proteins of the complement system were significantly enriched. ConclusionAH proteome of POAG patients shows strong activation of the immune system. In addition, analysis suggests dysregulation of folate metabolism and dysregulation of selenium as underlying contributors. In view of their glaucoma surgery, POAG patients of subgroup 1 most likely are progressive whereas POAG patients in subgroup 2 most likely have stable POAG. The proteome difference between these subgroups suggests that the complement system plays a role in POAG progression.
Highlights
Glaucoma is a neurodegenerative disorder characterized by progressive loss of retinal ganglion cells and their axons, resulting in visual field loss (Quigley and Broman, 2006; Tham et al, 2014)
We divided the untargeted studies into 2 subgroups based on the type of surgery the primary open angle glaucoma (POAG) patients underwent at time of aqueous humor (AH) collection
The remaining nine studies were untargeted proteome studies using LCMS/MS that were divided into a group of POAG patients that underwent GFS (subgroup 1 (Adav et al, 2018; Kaur et al, 2018; Kliuchnikova et al, 2016), and a group that underwent cataract extraction surgery (subgroup 2 (Ji et al, 2015; Kaeslin et al, 2016; Salamanca et al, 2018; Sharma et al, 2018),)
Summary
Glaucoma is a neurodegenerative disorder characterized by progressive loss of retinal ganglion cells and their axons, resulting in visual field loss (Quigley and Broman, 2006; Tham et al, 2014). Since IOP and AH play such an important role in POAG, it is assumed that AH composition changes during POAG development and progression Identifying these changes could give more insight in the underlying disease mechanism and could be used as a biomarker or risk factor for POAG. We observed 73 differentially expressed proteins in subgroup 1 and 87 differentially expressed proteins in subgroup 2 Both subgroups were characterized by activation of the acute immune response, dysregulation of folate metabolism and dysregulation of the selenium micronutrient network. Analysis suggests dysregulation of folate metabolism and dysregulation of selenium as underlying contributors In view of their glaucoma surgery, POAG patients of subgroup 1 most likely are progressive whereas POAG patients in subgroup 2 most likely have stable POAG. The proteome difference between these subgroups suggests that the complement system plays a role in POAG progression
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