Effects of Regorafenib, a Multi-Kinase Inhibitor, on Conjunctival Scarring in a Canine Filtration Surgery Model in Comparison with Mitomycin-C.

Abstract

Regorafenib eye drops were developed for treating age-related macular degeneration. This study aimed to investigate the effects of this multi-kinase inhibitor on intraocular pressure (IOP), bleb formation, and conjunctival changes in a canine filtration surgery model. Glaucoma filtration surgery models were created in 24 eyes of 24 beagles. In experiment 1 (Ex 1), regorafenib eye drops (regorafenib group: n = 6) or a vehicle (control group, n = 6) were instilled twice daily for 4 weeks postoperatively. In experiment 2 (Ex 2), regorafenib eye drops were instilled as in Ex 1 (regorafenib group: n = 6) for 12 weeks while conventional intraoperative mitomycin-C (MMC) was utilized (MMC group: n = 6), In Ex 1, only the regorafenib group showed significant IOP reduction with a significantly higher bleb score. Subconjunctival area, collagen density, vessels, and cells showing proliferation and differentiation were lower in subconjunctival tissue in the regorafenib group. In Ex 2, no significant difference was found in IOP reduction and bleb formation between the regorafenib and MMC groups; bleb walls were significantly thicker and collagen density and vessels were higher in the regorafenib group; and no differences were observed in the above-mentioned cells. Thus, regorafenib might be a better alternative to MMC for creating thicker and less ischemic blebs in glaucoma filtration surgery.

• Authors: Emika Nemoto, Shota Kojima, Tetsuya Sugiyama, Denan Jin, Shinji Takai, Michiko Maeda, Ryohsuke Kohmoto, Mari Ueki, Hidehiro Oku, Tsunehiko Ikeda
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 1 (Dec 20 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 31861830 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antimetabolites
• Phenylurea Compounds
• Protein Kinase Inhibitors
• Pyridines
• regorafenib
• Mitomycin

Topics

• Animals
• Antimetabolites (therapeutic use)
• Conjunctiva (drug effects, pathology)
• Disease Models, Animal
• Dogs
• Filtering Surgery (methods)
• Glaucoma (drug therapy, pathology, surgery)
• Intraocular Pressure (drug effects)
• Mitomycin (therapeutic use)
• Phenylurea Compounds (therapeutic use)
• Protein Kinase Inhibitors (therapeutic use)
• Pyridines (therapeutic use)