Sustained Ocular Antioxidant Therapy with Thiolated Catalase for Intervention of Corneal Injuries and Atopic Conjunctivitis

Aberrant redox homeostasis owing to overproduction of reactive oxygen species (ROS) within the ocular microenvironment is critically implicated in the pathogenesis of various inflammatory ocular disorders or injuries. Previously reported antioxidant strategies, such as small-molecule ROS scavengers or nano-enzymes, are challenged by rapid tear turnover. Herein, we demonstrate that by decomposing hydrogen peroxide, the most stable form of ROS, catalase (CAT) shows superior ability in mitigating oxidative stress compared to the widely-applied antioxidant enzyme superoxide dismutase (SOD), and is able to effectively clear different types of ROS to restore redox homeostasis. We then developed a thiolation strategy for CAT, and the obtained CAT-SH could form cleavable disulfide bonds with mucins on the ocular surface to allow greatly prolonged retention and sustained ROS scavenging. Such CAT-SH eyedrop treatment significantly improves prognosis in acute corneal alkali burn model, and demonstrates compelling efficacy in treating allergic conjunctivitis by effectively stabilizing mast cells and attenuating allergic responses. In both models, CAT-SH eyedrops offer improved therapeutic performances compared to respective clinically used eyedrop therapies. Meanwhile, such CAT-SH eyedrops exhibit exceptional safety profiles. Our work thus offers a highly promising yet simple eyedrop therapy to treat ocular surface injuries or inflammatory diseases with significant translational potential.