Unveiling the levels and significance of different serpin family proteins in aqueous humor dynamics

Abstract Background Alterations in the constituents of the aqueous humor (AH) are associated with various ocular pathologies, including primary open-angle glaucoma (POAG). AH contains a variety of immunomodulatory molecules, including serine protease inhibitors (serpins), which regulate several proteolytic cascades such as coagulation, angiogenesis, and inflammation. The purpose of this study was to examine the levels of different serpins in human AH and their association with POAG pathology. Methods The abundance of all 37 serpins was determined using LC-MS/MS analysis in 289 human AH samples (cataract: n = 209; POAG: n = 80). The potential involvement of these serpins in POAG was examined by correlating their levels with clinical parameters such as intraocular pressure (IOP) and optic nerve damage. Results Among the 37 serpins present in the human proteome, 26 were detected in aqueous humor. The thirteen most abundant serpins in AH include SERPINA1, SERPINF1, SERPINC1, SERPINA3, SERPING1, AGT, SERPINF2, SERPINA4, SERPINA6, SERPIND1, SERPINI1, SERPINA7, and SERPINA5. Seven serpins were downregulated in subjects with POAG, including SERPINI1 (FC = 0.26), SERPINA4 (FC = 0.40), SERPINA6 (FC = 0.42), SERPINA7 (FC = 0.46), SERPINC1 (FC = 0.74), AGT (FC = 0.76), and SERPING1 (FC = 0.78). Conclusion This study highlights significant alterations in serpin levels within the AH of individuals with POAG. Sex-specific and race-specific differences in the levels of several serpins were also observed. Further studies are needed to clarify the specific mechanisms by which these serpins may contribute to POAG progression and to investigate their potential clinical relevance.