Abstract
PURPOSE: To evaluate antioxidant capacity in aqueous humor (AH), trabecular meshwork (TM), and lens epithelium (LE) from patients with primary open-angle glaucoma and cataract and to assess associations with race and disease severity. METHODS: In this prospective cross-sectional study, two surgical cohorts undergoing cataract with glaucoma surgery provided either AH or paired TM/LE. AH total reactive antioxidant potential and ascorbic acid were measured. In paired TM and LE from the same eye, qPCR assessed nuclear factor erythroid 2-related factor 2 (NRF2), catalase (CAT), and superoxide dismutase 2. For AH, group comparisons used Welch's t tests or Mann-Whitney tests, and severity-stratified analyses used Race × Severity two-way ANOVA with Šídák correction. For qPCR, within-eye differences were calculated as Δ(TM - LE); race comparisons used Welch's t tests for each marker, with Šídák correction across the three markers. RESULTS: AH was analyzed from 106 eyes (Black n = 37; White n = 69); no race differences remained after Race × Severity modeling with Šídák adjustment. Paired TM/LE qPCR was analyzed from 42 eyes (Black n = 21; White n = 21). In Black eyes, NRF2 and CAT were lower in TM relative to matched LE (both P < 0.0001), whereas no such paired tissue differences were detected in White eyes. The within-eye difference Δ(TM - LE) was more negative in Black than White eyes for NRF2 (P = 0.0001) and CAT (P = 0.0024). Superoxide dismutase 2 showed no race-associated difference. CONCLUSIONS: AH antioxidant measures showed limited race-associated differences, whereas paired TM/LE profiling revealed tissue- and marker-specific expression differences most evident in Black patients. These compartment-specific signatures warrant validation in larger prospective cohorts.