Mitomycin C-loaded PTMC15–F127–PTMC15 hydrogel maintained better bleb function after filtering glaucoma surgery in monkeys with intraocular hypertension

Abstract

There is an unmet need for a safer and more effective approach for antimetabolite application to prevent bleb fibrosis after glaucoma filtering surgery. Here, we utilized our previously developed thermosensitive sustained-release agent, mitomycin C-loaded poly(trimethylene carbonate)15–F127–poly(trimethylene carbonate)15 (MMC-hydrogel), aiming to further evaluate the efficacy and safety of MMC-hydrogel in high intraocular pressure (IOP) primate eyes. Twelve primate eyes after high IOP induction were randomly divided into three groups, which respectively received phosphate-buffered saline (PBS)-hydrogel, MMC-hydrogel, and MMC treatment during trabeculectomy. IOP and bleb volume were measured using a Tonopen and anterior segment optical coherence tomography over 28 days. At the end of the experiment, all experimental primate eyes were enucleated. Histopathology and immunohistochemistry were performed to reveal myofibroblast cells and collagen deposition of filtering blebs. The MMC-hydrogel group had satisfactory IOP control (9.25 ± 4.80 mmHg) and maintained well-functioning blebs for a longer time. Fibrosis and scarring were significantly alleviated in this MMC-hydrogel group. There was no obvious toxicity to ocular surfaces or intraocular structures. Taken together, these data suggest that PTMC15–F127–PTMC15-loaded MMC-hydrogel plays a role in functional maintenance and scarring inhibition, showing high efficacy in reducing post-filtering surgery bleb fibrosis. This MMC-hydrogel may offer a new solution for filtering bleb management after glaucoma surgery.