Elevated YKL-40 serum levels may contribute to wet age-related macular degeneration via the ERK1/2 pathway.

Choroidal neovascularization (CNV) is a key characteristic of wet age-related macular degeneration (AMD) that can lead to severe vision loss in the elderly. Anti-VEGF therapy is currently the premier strategy for wet AMD, but it has limited efficacy. Previous studies have shown that chitinase-3-like-1 (YKL-40) can promote microangiogenesis and inflammation, but its effect on CNV formation has not yet been studied. Here, we investigated the potential role of YKL-40 in wet AMD and the underlying mechanism(s). We report that the serum expression of YKL-40 in wet AMD patients was significantly higher than that in control patients and was positively correlated with VEGF expression, indicating that YKL-40 may participate in the development of wet AMD. In addition, YKL-40 and VEGF expression levels were observed to be increased and the ERK1/2 pathway activated in the neuroretinal (NR) and RPE/choroid tissues of mice with laser-induced CNV. The YKL-40 and phosphorylated protein levels of the ERK1/2 pathway were decreased after intravitreal injection with an anti-YKL-40 antibody, suggesting that anti-YKL-40 could inhibit the activation of the ERK1/2 pathway. These results indicate that YKL-40 may serve as a novel target for the diagnosis and treatment of wet AMD.