Soy isoflavones inhibits MMPs expression in keratoconus keratocytes through NF-κB pathway

Keratoconus (KC) is a progressive ocular disorder characterized by central corneal thinning and anterior protrusion. The available clinical treatment options for KC remain limited, and there is currently a paucity of effective pharmacological intervention strategies. To address this therapeutic challenge, we identified through small-molecule screening that soy isoflavones (Si) significantly inhibit the release of corneal matrix metalloproteinases (MMPs) and enhance the biomechanical stiffness of the corneal stroma. Notably, the major MMPs implicated in driving KC progression, such as MMP-1, MMP-2, MMP-3, and MMP-9, can be effectively suppressed by Si. Mechanistic studies revealed that Si regulates MMPs activity by downregulating the nuclear factor-kappa B signaling pathway. Animal experiments further confirmed that this compound can reverse type II collagenase-induced corneal thinning. Collectively, these in vitro and in vivo findings suggest that Si treatment may represent a novel therapeutic strategy for intervening in keratoconus progression.