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Updated: Sep 20, 2026
Induction of Ocular Surface Inflammation and Collection of Involved Tissues
Published on: August 4, 2022
Mucoadhesive recombinant human catalase for dry eye disease: From protein engineering to first-in-human study
Ming Shao1, Yiteng Lu2, Wenjie Xie3
1Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory of Advanced Healthcare Materials & Devices, Soochow University, Suzhou 215123, China; Department of Ophthalmology, Eye & ENT Hospital, State Key Laboratory of Brain Function and Disorders, MOE Frontiers Center for Brain Science, Fudan University, Shanghai 200031, China.
Background:
Oxidative stress caused by excess reactive oxygen species (ROS) plays a key role in the progression of dry eye disease (DED), yet no approved DED therapy directly eliminates ROS. Here, we develop an antioxidant biologic with enhanced ocular-surface retention by thiol engineering of recombinant human catalase (hCAT) as a new ROS-scavenging eye drop therapy for DED.
Methods:
Thiolated hCAT (hCAT-SH) was characterized for activity, stability, mucin interaction, and ocular retention. Efficacy, mechanism, and safety were evaluated in mouse, rabbit, and rat studies, followed by a randomized, double-blind, placebo-controlled first-in-human trial in 30 patients with DED.
Findings:
With formulation optimization, hCAT-SH maintained enzymatic activity and formulation stability, while exhibiting enhanced mucin binding and prolonged corneal retention. In mouse DED models, hCAT-SH reduced oxidative stress, accelerated epithelial repair, restored tear secretion, and modulated inflammatory and barrier-repair pathways distinct from cyclosporine. In rabbits, exposure remained predominantly ocular with favorable repeated-dose tolerability. Clinically, 0.1 mg/mL hCAT-SH significantly improved corneal fluorescein staining, reduced tear cytokine levels and corneal dendritic cell density versus placebo, and raised no treatment-related safety concerns.
Conclusions:
hCAT-SH is a carrier-free, long-retained H2O2-scavenging biologic, with integrated preclinical and first-in-human evidence supporting further development as a new DED drug.
Funding:
National Natural Science Foundation of China; National Technology Innovation Center for Biopharmaceuticals; Jiangsu Key R&D Program; National Key R&D Program of China; Shanghai "Dawn" Program; Shanghai Science and Technology Innovation Action Plans; Shanghai Municipal Commission of Health; Shanghai High-Quality Development Plan for Science and Technology Industry; and Macao FDCT.
