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

Abstract

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.