Bortezomib Inhibits Cellular Proliferation and Inflammation in a Mouse Model of Proliferative Vitreoretinopathy

Proliferative vitreoretinopathy (PVR), a challenging complication of rhegmatogenous retinal detachment surgery, lacks effective pharmacological interventions; therefore, necessitating new therapeutic strategies. This study evaluates bortezomib, a proteasome inhibitor known for its anti‐proliferative and anti‐inflammatory properties, using in vitro and in vivo models. In vitro experiments with ARPE‐19 cells revealed that bortezomib significantly reduced migration, proliferation, and contraction, key processes in PVR pathogenesis. In a mouse model of PVR, bortezomib treatment mitigated clinical and histological presentations, showing a protective effect. Mechanistic investigations demonstrated that bortezomib inhibited the nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathway by reducing its activation and preserving its inhibitor, IκB. Additionally, bortezomib modulated inflammatory responses by suppressing pro‐inflammatory mediators such as MCP‐1, IP‐10, IL‐4, IL‐13, and IL‐17 while enhancing anti‐inflammatory cytokines like IL‐10. These findings highlight the potential of bortezomib as a promising therapeutic option for managing PVR.