Abstract
Purpose :
Microglial activation has emerged as a critical event contributing to retinal ganglion cell loss in glaucoma. Apolipoprotein E (APOE), the major apolipoprotein in the brain, and Galectin-3 (Gal-3), a secreted carbohydrate-binding lectin, have been identified as molecules critical for microglial cytotoxicity in mouse models of glaucoma. In this study, we aim to examine the role of APOE and Gal-3 in human disease by analyzing their concentrations in aqueous humor (AH) collected from glaucoma patients and healthy controls.
Methods :
AH was collected from 71 patients at the start of surgery, including 57 glaucoma patients undergoing various ophthalmic procedures and 14 control patients undergoing routine cataract surgery. APOE and Gal-3 levels were quantified by enzyme-linked immunosorbent assay and total protein concentration by bicinchoninic acid (BCA) assay. Patients’ medical records were carefully reviewed to collect relevant preoperative data. Descriptive statistics, Pearson’s correlation coefficient, and multivariate linear regression analyses were conducted to characterize associations between clinical and demographic variables and APOE and Gal-3 levels.
Results :
APOE and Gal-3 levels were significantly elevated in the AH of glaucoma patients (1.64 +/- 1.45 μg/mL and 2.33 +/- 2.09 ng/mL, respectively) compared to controls (0.40 +/- 0.19 μg/mL, 0.92 +/- 0.81 ng/mL) [p<0.001; p=0.004]. APOE and Gal-3 levels were moderately positively correlated across the entire cohort (r=0.65, p<0.001). No association was observed between APOE and total protein or Gal-3 and total protein, indicating that APOE and Gal-3 levels were not increased in glaucomatous AH due to nonspecific protein accumulation (p>0.3). Multivariate linear regression analyses revealed significant associations between Gal-3 and maximum recorded intraocular pressure measurement (p=0.009), and between APOE and number of past ophthalmic surgeries (p=0.031).
Conclusions :
Our findings demonstrate that APOE and Gal-3 are increased in the AH of glaucoma patients and significantly correlate with clinical measures of glaucoma severity. Thus, these molecules could serve as biomarkers to identify patients who may benefit from microglia-based neuroprotective glaucoma therapies.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.