June 2020
Volume 61, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2020
Neuroprotective Effects of Novel Compound 056 in optic nerve degeneration model
Author Affiliations & Notes
  • Shun-Ping Huang
    Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
  • Jia-Ying Chien
    Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan
    Molecular Biology and Human Genetics, Tzu Chi University, Hualien, Taiwan
  • Footnotes
    Commercial Relationships   Shun-Ping Huang, None; Jia-Ying Chien, None
  • Footnotes
    Support  MOST Grant 105-2628-B-320-002-MY3
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 2487. doi:
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      Shun-Ping Huang, Jia-Ying Chien; Neuroprotective Effects of Novel Compound 056 in optic nerve degeneration model. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2487.

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      © ARVO (1962-2015); The Authors (2016-present)

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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.

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