Abstract
Purpose :
Our prior study of human trabecular meshwork (TM) demonstrated racial disparities of oxidative stress/damage. This experimental study aims to compare antioxidant protection by the transcription factor nuclear factor E2-related factor 2 (Nrf2) in TM from healthy donors and primary open angle glaucoma (POAG) patients stratified by race (Black/White).
Methods :
Following informed consent, POAG TM tissue and lens capsule were collected from patients undergoing cataract and goniotomy surgery. Control TM was obtained from donors. Patient and donor data (self-reported race, age) were recorded. Antioxidant enzymes superoxide dismutase (SOD2), catalase (CAT), and transcription factor Nrf2 were analyzed in donor TM tissues by both qPCR and Western blot. For patient specimens, only qPCR was performed for these gene expressions due to limited quantity. GAPDH (housekeeping gene) was used for quantitative analysis. Unpaired t-test was used for statistical analysis.
Results :
Our data indicate significantly lower Nrf2 and SOD2 expression in Black compared to White donor TM (p=0.02 and p=0.04, respectively; n=3/group), with no racial difference observed in CAT expression (p=0.06). Western blot analysis also revealed reduced Nrf2 and SOD2 levels in Black donor TM compared to White (p=0,003 and p=0.04, respectively; n=6/group). In POAG TM specimens, only Nrf2 showed significantly lower expression in Black compared to White patients (p=0.0001; n=6), while SOD 2 and CAT exhibited no racial differences. Lens capsule speciimens displayed no statistical differences in expression of these genes.
Conclusions :
This investigation into reactive oxygen species (ROS)-related pathways focused on major antioxidant enzymes (SOD2, CAT) and traanscriptional factor Nrf2, with analysis of both RNA and protein levels. Our findings indicated reduction of the key antioxidant defense regulator Nrf2 in both Black donor TM (healthy) and POAG patient TM. Lens capsules did not demonstrate this racial difference, possibly indicating a tissue-specific discovery. These preliminary results suggest Black patients may experience chronic elevation of mitochondrial-associated ROS production, combined with TM-specific Nrf2 dysregulation. This imbalance in redox signaling could potentially contribute to elevated oxidative stress/damage in TM tissue, thereby increasing the risk of POAG among Black individuals.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.