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

Area of Science:

• Ophthalmology
• Pharmacology
• Cell Biology

Background:

• Proliferative vitreoretinopathy (PVR) is a severe complication following rhegmatogenous retinal detachment surgery.
• Current treatments for PVR are limited, necessitating novel therapeutic approaches.

Purpose of the Study:

• To investigate the efficacy of bortezomib, a proteasome inhibitor, as a potential treatment for PVR.
• To evaluate bortezomib's effects on key cellular processes involved in PVR pathogenesis and its anti-inflammatory properties.

Main Methods:

• In vitro studies using ARPE-19 cells to assess bortezomib's impact on cell migration, proliferation, and contraction.
• In vivo experiments using a mouse model of PVR to evaluate bortezomib's therapeutic effects.
• Mechanistic studies to elucidate bortezomib's effects on the NF-κB pathway and inflammatory mediator expression.

Main Results:

• Bortezomib significantly reduced migration, proliferation, and contraction of ARPE-19 cells in vitro.
• Bortezomib treatment demonstrated protective effects in a mouse model of PVR, mitigating clinical and histological signs.
• Mechanistically, bortezomib inhibited the NF-κB pathway and modulated the expression of pro- and anti-inflammatory cytokines.

Conclusions:

• Bortezomib exhibits significant anti-proliferative and anti-inflammatory effects relevant to PVR.
• Bortezomib shows potential as a novel pharmacological intervention for managing proliferative vitreoretinopathy.