Dimercaprol attenuates oxidative stress-induced damage of retinal ganglion cells in an in vitro and in vivo model of traumatic optic neuropathy

Abstract

Traumatic optic neuropathy (TON) is a prevalent form of optic neuropathy, which is a significant cause of irreversible blindness. To date, effective therapeutic interventions for TON are lacking, highlighting the urgent need for the development of new therapeutic drugs. In this study, a compound library comprising 480 Food and Drug Administration (FDA)-approved drugs was screened to identify potentially effective therapeutic drugs for TON. We reported that dimercaprol (DMP), an FDA-approved drug, can reduce L-Glutamic acid (Glu) and hydrogen peroxide (H₂O₂)-induced injury in a retinal cell line (R28 cell). Our findings further demonstrated that intracellular reactive oxygen species (ROS) and acrolein, a lipid peroxide, are major contributors to apoptosis-induced cell death in vitro. A series of functional assays revealed that DMP can inhibit apoptosis-induced by Glu via scavenging of intracellular ROS and acrolein in R28 cells and primary cortical neurones. Notably, DMP inhibited retinal ganglion cell complex (GCC) thinning and retinal ganglion cell (RGC) loss resulting from optic nerve crush (ONC) injury in vivo. Moreover, DMP effectively eliminated ONC-induced acrolein in the retina and inhibited RGC apoptosis in vivo. In conclusion, intracellular ROS and acrolein play significant roles in RGC loss in TON, and DMP effectively inhibits RGC apoptosis-induced by the oxidative stress pathway in vitro and in vivo. Therefore, DMP has emerged as a potential new therapeutic drug against TON.