Abstract
Purpose :
The aim of this study is to explore the neuroprotective effects of compound 056 on a rat model of optic nerve crush
Methods :
ONC was induced by microvascular clipping the optic nerve for 30 secs to mimic the traumatic optic nerve injury in adult male Wistar rats. In this study, Compound 056 is used as an inhibitor of E3 ubiquitin ligase. After ONC, rats were treated immediately with Compound 056 (subcutaneously once with a dosage of 15mg/kg) or Phosphate Buffered Saline (PBS). Two weeks after the crush, the results were analyzed by several approaches including functional, cellular, molecular and structural studies.
Results :
Preserved visual function assessed by flash visual evoked potential was observed in Compound 056 treated groups. Retrograde fluorogold labeling and TUNEL assay showed increased survival of RGCs and reduced RGC apoptosis in Compound 056 treated groups respectively.Reduced optic nerve head edema and reduced infiltration of blood-borne macrophages in the optic nerve in Compound 056 treated groups were determined by Optical Coherence Tomography and ED1 staining respectively. Inhibition of the NF-κB pathway mediated inflammation and upregulated autophagy-mediated neuroprotection to the RGCs was checked by western blotting. BAG1 and BAG3 protein levels in western blot confirmed the downregulation of ubiquitin/proteasome system (UPS) and upregulation of autophagy system respectively
Conclusions :
In conclusion, this study would increase our understanding into the role of Compound 056 as a neuro-protectant which can rescue the RGCs in rat ONC model
This is a 2020 ARVO Annual Meeting abstract.