The role of LOX and LOXL2 in wound healing after glaucoma filtration surgery

Abstract

Abstract Purpose Lysyl oxidase (LOX) and lysyl oxidase‐like protein 2 (LOXL2) are involved in the crosslinking of collagen and elastin. We have shown that LOX and LOXL2 were upregulated after glaucoma surgery. The aim of this study was to investigate the efficacy of anti‐LOX (M64) and of anti‐LOXL2 (M20) antibodies (Arresto Biosciences) in a rabbit model of trabeculectomy. Methods Treatment with the antibodies or control (PBS) was initiated on day 0 after surgery by giving an intracameral injection (0.6 mg) and a subconjunctival (SC) injection (0.3 mg). Thereafter the antibodies were injected twice a week SC (0.3 mg) until 30 days after the surgery. The outcome of the treatment was studied by clinical investigation (IOP, bleb area and bleb survival) and by analysis of angiogenesis (CD31), inflammation (CD45) and collagen deposition (Sirius Red). Results Both antibodies were able to significantly improve surgical outcome by increasing bleb area and bleb survival compared to control (p<0.001). Analyses of the different stainings showed a significant reduction in angiogenesis (47%; p=0.01), inflammation (34%; p=0.0003) and fibrosis (16%; p=0.01), respectively, in the anti‐LOXL2 treated group compared to control. Anti‐LOX antibody resulted in a significant reduction only in collagen deposition (22%; p=0.0009 compared to control). Conclusion These results showed that LOX and LOXL2 are important in ocular wound healing. We also provide evidence on effectiveness of repeated anti‐LOXL2 injections after trabeculectomy. The anti‐LOXL2 antibody was able to improve surgical outcome by reducing angiogenesis, as well as inflammation and collagen deposition. These new insights may have important therapeutic implications for glaucoma surgery. Commercial interest