July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Proteomic alterations supporting the altered bioenergetic profile of astroglia in glaucoma
Author Affiliations & Notes
  • Gulgun Tezel
    Ophthalmology, Columbia University, New York, New York, United States
  • Xiangjun Yang
    Ophthalmology, Columbia University, New York, New York, United States
  • Jian Cai
    University of Louisville, Louisville, Kentucky, United States
  • Mine Baris
    Ophthalmology, Columbia University, New York, New York, United States
  • Jon B Klein
    University of Louisville, Louisville, Kentucky, United States
  • Footnotes
    Commercial Relationships   Gulgun Tezel, None; Xiangjun Yang, None; Jian Cai, None; Mine Baris, None; Jon Klein, None
  • Footnotes
    Support  NIH Grant 1R01EY028153, RPB
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3788. doi:
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      Gulgun Tezel, Xiangjun Yang, Jian Cai, Mine Baris, Jon B Klein; Proteomic alterations supporting the altered bioenergetic profile of astroglia in glaucoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3788.

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

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Abstract

Purpose : Uncovering the key molecular processes in specific cell types is crucial to treat neurodegeneration in glaucoma. This study aimed to analyze cell type-specific proteomic datasets to determine alterations in the bioenergetic profile of retina and optic nerve head astroglia during neurodegeneration in glaucoma.

Methods : We modeled glaucoma by IOP elevation induced by anterior chamber microbead/viscoelastic injections in mice. Besides the analysis of neuron survival/function, protein samples obtained from retina and optic nerve head astroglia (after enrichment by immunomagnetic cell selection) were analyzed by isotope labeling-based quantitative LC-MS/MS at 12 weeks of ocular hypertension. Proteomic data for selected proteins were validated in mouse eyes and human donor eyes (with or without glaucoma) by immunoblotting and immunohistochemistry.

Results : High throughput datasets from analysis of astroglial protein samples (with false discovery rate of <1%) indicated various molecules presenting an over two-fold change (p<0.05) with ocular hypertension. Parallel to prominent inflammatory activity, knowledge-based analysis of proteomic datasets by IPA indicated reduced mitochondrial activity and down-regulation of mitochondrial oxidative phosphorylation in ocular hypertensive samples. Instead, astroglial proteome in ocular hypertensive samples displayed enhanced glycolytic metabolism as characterized by increased expression of proteins involved in glucose uptake (GLUT1) and increased expression of enzymes catalyzing the rate-limiting steps of glycolysis (hexokinase, phosphofructokinase, pyruvate kinase). An enzyme critical for glycogen breakdown (glycogen phosphorylase) was also increased in expression by more than two-fold. Despite overexpression of glycolysis proteins, however, molecules linked to monocarboxylate export (MCT1, MCT4) exhibited decreased or unchanged expression in ocular hypertensive samples of astroglia.

Conclusions : Findings of this study suggest a shift in the metabolic profile of glaucomatous astroglia towards increased glycolysis. This shift may be due to increase in their own energy needs under glaucoma-related cellular stress and inflammatory activity (and/or insufficient nutrient supply) and may lead to decreased metabolic support to neurons. These findings stimulate additional studies to further explore pathogenic and therapeutic implications of metabolic vulnerability in glaucoma.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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