Effect of 3',4'-Dihydroxyflavonol Eye Drops in a Rat Model of Dispase-Induced Proliferative Vitreoretinopathy.
Elsa C Chan, Cheng Zeng, Chi D Luu, Carla J Abbott, Nicholas T Chan, Keshava K Datta, Nicholas Williamson, Penelope J Allen, Jennifer C Fan Gaskin
Abstract
Open Access(1) Background: Proliferative vitreoretinopathy (PVR) is the most common cause of failure in retinal detachment surgery and often leads to blindness. Oxidative stress is known to contribute to scar formation; therefore, reducing oxidative stress may protect against PVR development. This study investigated the therapeutic effects of the antioxidant 3',4'-dihydroxyflavonol (DiOHF) in two preclinical models of PVR. (2) Methods: A retinal pigment epithelial cell line (ARPE-19) was used to investigate the anti-fibrotic effects of DiOHF. PVR was induced in one eye of each animal using dispase. Animals then received either vehicle or DiOHF eye drops in both eyes for 28 days. Eyes were harvested for mass spectrometry to perform proteomic analysis or to quantify tissue accumulation of DiOHF. Proteomic analysis was also performed in ARPE to validate these findings. (3) Results: In DiOHF-treated eyes with induced PVR, proteomic profiles showed reduced fibrosis, inflammation, cell migration, and oxidative stress compared with vehicle-treated PVR eyes. The in vitro studies confirmed that DiOHF inhibited wound healing responses, cell contraction, proliferation, and the generation of reactive oxygen species in ARPE-19 cells. Proteomic analysis in ARPE-19 also showed a similar trend. (4) Conclusions: This study provides compelling evidence that DiOHF eye drops offer protective effects against PVR in preclinical models.