Abstract
Purpose :
Proliferative vitreoretinopathy (PVR) is a complication in patients who undergo surgeries to correct rhegmatogenous retinal detachment and has been the major cause of ultimate surgical failure. However, the effective pharmacological treatment to prevent PVR is still unavailable. Bortezomib, a proteasome inhibitor, is a cancer drug for the treatment of multiple myeloma. In this study, we investigated whether the proteasome inhibitor bortezomib ameliorated experimental PVR in mice by suppressing the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB).
Methods :
We examined the effects of bortezomib on cell migration, proliferation and contraction in vitro using the human retinal pigment epithelial cell line (ARPE-19). Then we tested the bortezomib treatment on experimental PVR in vivo using the mouse model. We checked the activation of NF-κB on the ARPE-19 cells and mouse retinas after PVR induction with or without bortezomib treatment to investigate the related mechanism. We also checked the levels of NF-κB related chemokines, monocyte chemoattractant protein-1 (MCP-1) and Interferon gamma-induced protein 10 (IP-10) in the mouse retinas after PVR induction with or without bortezomib treatment.
Results :
We found that bortezomib suppressed the migration, proliferation, and contraction of ARPE-19 cells in vitro. Then, we found that bortezomib ameliorated the severity of experimental PVR induced by ARPE-19 cells in mice. The bortezomib treatment suppressed the activation of NF-κB in both ARPE-19 cells and mouse retinas after PVR induction. The levels of both NF-κB related chemokines, MCP-1 and IP-10, were also suppressed significantly with bortezomib treatment in the mouse retinas after PVR induction.
Conclusions :
In this study, we revealed that bortezomib treatment could ameliorate experimental PVR by suppressing NF-κB activation in ARPE-19 cells and mouse retinas. The NF-κB related chemokines, both MCP-1 and IP-10, were also suppressed in the retinas of PVR mice with bortezomib treatment. The results suggested a potential role of bertezomib for the treatment of human PVR in the future.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.