De-Quan Li, Stephen Pflugfelder, Jin Li and Ruzhi Deng
Ocular Surface Center, Cullen Eye Institute, Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA
Blueberries have been recognized to benefit health with preventive effects from various diseases. However, no study has investigated their effects on eye and ocular diseases. This study was to explore potential anti-inflammatory effects of blueberry component pterostilbene (PS) on dry eye using an in vitro culture model of human corneal epithelial cells (HCECs) exposed to hyperosmotic stress. Hyperosmolarity has been known to induce inflammatory and oxidative stress in HCECs. The addition of PS significantly reduced the expression of pro-inflammatory markers, TNF-α, IL-1β, IL-6, MMP-2 and MMP-9 in HCECs exposed to hyperosmotic medium. Pre-treatment with PS (5 to 20µM) suppressed overproduction of reactive oxygen species (ROS) in a dose-dependent manner. Interestingly, PS significantly decreased the levels of oxidative damage biomarkers, malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), aconitase-2 and 8-hydroxydeoxyguanosine (8-OHdG). Furthermore, PS was found to rebalance homeostasis between oxygenases and anti-oxidative enzymes by decreasing cyclooxygenase 2 (COX2) expression and restoring the activity of antioxidant enzymes, superoxide dismutase 1 (SOD1) and peroxiredoxin-4 (PRDX4) during hyperosmotic stress. These findings demonstrate for the first time that blueberry component pterostilbene protects the human cornea from hyperosmolarity-induced inflammation and oxidative stress, suggesting the therapeutical potential to dry eye disease.
This study was supported in part by NIH NEI Grants R01EY023598 (DQL), EY011915 (SCP) and Core Grant for Vision Research EY002520, Eye Bank Association of America (DQL), Lions Foundation for Sight, Research to Prevent Blindness, Oshman Foundation, and William Stamps Farish Fund.