Purpose: The purpose of this study was to explore the involvement of two known mediators of the apoptotic processes in ganglion cells, the proteins alpha-2-macroglobulin (α2M) and tumor necrosis factor-α (TNF-α), in the pathogenesis of primary open-angle glaucoma (POAG) and pseudoexfoliation (PXF) syndrome. Methods: Aqueous humor samples were collected at the beginning of cataract surgery. Levels of α 2 M and TNF-α were measured using western blot analysis and expressed as fold values. Commercially available pure α 2 M protein and TNF-α were used as controls. For digital quantification, nitrocellulose membranes were scanned and analyzed using Image J software. Results: Levels of α2M level were measured in 61 samples, which included 18 with PXF, 15 with POAG, and 28 controls. Mean levels of α 2 M in the aqueous humor of patients with PXF without glaucoma were comparable to control levels and lower than for patients with POAG (0.63 ± 0.1; 0.6 ± 0.05; and 0.92 ± 0.1, respectively, P = 0.05). TNF-α levels were measured in 25 aqueous humor samples including eight with PXF, seven with POAG, and 10 controls. TNF-α protein fold level values were higher in patients with glaucoma, with and without PXF, and compared to control values (0.77 ± 0.1 and 0.5 ± 0.4 compared to 0.06 ± 0.01, respectively, P = 0.05 post-log conversion). Conclusion: This work further documents the role of α2M protein in the apoptotic process in ganglion cells related to increased IOP but marks its absence in PXF material accumulation without glaucoma. Our findings regarding TNF-α levels may still suggest a role for this protein in PXF syndrome alone.
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