Neuroprotective Effect of Methylene Blue in a Rat Model of Traumatic Optic Neuropathy

<b>Background</b>: Traumatic optic neuropathy (TON) represents a major cause of vision loss worldwide, and treatment options are limited. Here, we study whether methylene blue (MB), a free radical scavenger, is able to prevent morphological and electrophysiological hallmarks of neuropathy in an animal model of TON. <b>Methods</b>: The left eyes of Wistar rats were subjected to intraorbital nerve crush (IONC) while the right ones were sham operated. The group of rats treated with MB (n = 16) received five intraperitoneal injections with 2.0 mg/kg MB in the 24 h following IONC while the control group (n = 16) received just vehicle (PBS) as a control. Twenty-one days after surgery, scotopic full field (scERG), scotopic oscillatory potentials (OP), photopic full field (phERG) and pattern (PERG) electroretinography were performed for retinal function assessment. Furthermore, the number of cell nuclei in the ganglion cell layer (GCL) was recorded in post mortem histological sections. <b>Results</b>: IONC induced very significant reductions in electrophysiological parameters including scotopic a- and b-wave, OPs, photopic b-wave, PhNR amplitude and N2 amplitude. In addition, it also generated a significant prolongation of the N2 implicit time, indicating a profound impact on retinal function. This was further corroborated by a very significant reduction in the number of neuronal nuclei in the GCL, suggesting an intense loss and functional impairment of retinal ganglion cells. MB treatment was able to prevent, partially or completely, all those parameters, indicating the efficiency of such approach. <b>Conclusions</b>: Since MB is already approved for clinical use and presents a high safety profile, it could be repurposed as a neuroprotective drug for ophthalmological applications once proper phase 2 clinical trials are accomplished.