Pirfenidone Reduces Intracochlear Fibrosis Caused by Cochlear Implantation in a Guinea Pig Model.

Abstract

While cochlear implants allow restoration of sound perception in individuals with severe to profound hearing loss, there remains significant variability in patient outcomes. A potential factor that may account for this unexplained variability is the formation of fibrosis within the cochlea after implantation. This study investigated the therapeutic potential of pirfenidone (PFD) in preventing cochlear implant-induced fibrosis and compared outcomes with dexamethasone (DEX) treated animals. The utility of PFD was determined in cultures of fibrocytes isolated from the inner ear of guinea pigs. Specifically, PFD-treatment significantly reduced p38 MAPK signalling, fibrocyte cell proliferation, migration and collagen III deposition in response to pro-fibrotic stimuli. In a guinea pig model, local hydrogel-mediated delivery of PFD to the round window at the time of implant surgery significantly reduced the amount of tissue reaction measured by micro-computed tomography at two months post-implantation (= 0.0297). Specifically, a 40% decrease in implant-induced tissue reaction was observed in PFD-treated animals compared to vehicle-treated controls. Notably, no evidence of ototoxicity was observed following PFD-treatment. In contrast, a 36% decrease in the amount of tissue reaction was measured in the DEX-treated control group (= 0.0436). Overall, these data demonstrate that PFD shows significant therapeutic potential in reducing cochlear implant-induced fibrosis.