June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Proteomics Analysis of Excitotoxicity Neurodegeneration in Retinal and Optic Nerves: N-Methyl-D-Aspartate-induced Ferroptosis, Autophagy, and Apoptosis
Author Affiliations & Notes
  • Lingge Suo
    Peking University Third Hospital Ophthalmology Department, Beijing, China
  • Di Zhang
    Peking University Third Hospital Ophthalmology Department, Beijing, China
  • Chun Zhang
    Peking University Third Hospital Ophthalmology Department, Beijing, China
  • Footnotes
    Commercial Relationships   Lingge Suo, None; Di Zhang, None; Chun Zhang, None
  • Footnotes
    Support  Chinese State Natural Science Foundation: NO. 81670851, Chinese State Natural Science Foundation: NO. 81970798
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 2971. doi:
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      Lingge Suo, Di Zhang, Chun Zhang; Proteomics Analysis of Excitotoxicity Neurodegeneration in Retinal and Optic Nerves: N-Methyl-D-Aspartate-induced Ferroptosis, Autophagy, and Apoptosis. Invest. Ophthalmol. Vis. Sci. 2021;62(8):2971.

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

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Abstract

Purpose : Various retinal disorders, such as glaucomatous, retinal ischemia reperfusion, and traumatic optic neuropathy, are involved in the pathogenesis of neurodegeneration via glutamate excitotoxicity. However, the proteomic characteristics and modulation of the neural microenvironment with NMDA-induced neurodegeneration in the retina and optic nerve remain incompletely understood.

Methods : We established a model of NMDA-induced injury by comparing the proteomes of phosphate-buffered saline (PBS)-operated, NMDA-operated and control groups. We performed mass spectrometry-based label-free quantitative mechanisms and identify key proteins that spatially regulate neural cell death related signaling pathways in the retina and optic nerve.

Results : Using LC-MS/MS proteomics analysis, we identified 3532 proteins in retinal tissues and 2593 proteins in optic nerve tissues. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, protein changes and energy metabolism in the retina and optic nerve tissue were comprehensively evaluated. Pearson’s correlation coefficients revealed the excellent biological reproducibility of the proteomic results. We identified the key cellular signaling events triggered by glutamate overstimulation based on protein-protein interaction analysis. We found that the ACSL3 (Q63151) and Prnp (P13852) proteins are key factors in ferroptosis regulation in the retina; the Gabarapl2 (P60522) protein is the key factor in autophagy in the optic nerve. In PRM validation, we confirmed 16 up- and downregulated key proteins among the different groups.

Conclusions : This study provides the basis for further studies linking NMDA-induced neural cell death in the retina and optic nerve and may shed light on the advanced molecular mechanism of disease biology and accelerated targeted therapy.

This is a 2021 ARVO Annual Meeting abstract.

 

 

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