July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Angiotensin II-Induced Oxidative Stress Inactivates Neuroprotective Mechanisms in Retina and Heightens Acute Vascular Adaptive Responses in Ophthalmic Artery: A Proteomic Perspective
Author Affiliations & Notes
  • Caroline Manicam
    Department of Ophthalmology, University Medical Centre Mainz, Mainz, Germany
  • Lars Straßburger
    Department of Ophthalmology, University Medical Centre Mainz, Mainz, Germany
  • David Herzog
    Department of Psychiatry and Psychotherapy & Focus Program Translational Neurosciences, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany
  • Norbert Pfeiffer
    Department of Ophthalmology, University Medical Centre Mainz, Mainz, Germany
  • Franz H Grus
    Department of Ophthalmology, University Medical Centre Mainz, Mainz, Germany
  • Natarajan Perumal
    Department of Ophthalmology, University Medical Centre Mainz, Mainz, Germany
  • Footnotes
    Commercial Relationships   Caroline Manicam, None; Lars Straßburger, None; David Herzog, None; Norbert Pfeiffer, None; Franz Grus, None; Natarajan Perumal, None
  • Footnotes
    Support  Deutsche Forschungsgemeinschaft (MA 8006/1-1)
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 5653. doi:https://doi.org/
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      Caroline Manicam, Lars Straßburger, David Herzog, Norbert Pfeiffer, Franz H Grus, Natarajan Perumal; Angiotensin II-Induced Oxidative Stress Inactivates Neuroprotective Mechanisms in Retina and Heightens Acute Vascular Adaptive Responses in Ophthalmic Artery: A Proteomic Perspective. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5653. doi: https://doi.org/.

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

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Abstract

Purpose : In recent years, there has been a renewed interest in the role of angiotensin II (Ang II) in mediating the pathogenesis of glaucoma. Despite its (patho)physiological importance, the molecular mechanisms underlying Ang II-mediated oxidative stress remain largely unexplored. This study tested the hypothesis that the retina (R) is more susceptible to Ang II-elicited oxidative insult than the ophthalmic artery (OA) in an in vitro experimental mouse model.

Methods : R and OA were isolated from male C57Bl/6J mice (n=15/group) and incubated overnight in medium containing either vehicle or Ang II (0.1 µM) at physiological conditions. Vascular proteins were extracted using our new in-house method specifically catered for robust protein extraction from microvascular samples and subjected to label-free quantitative mass spectrometry (MS)-based proteomics analysis. The acquired MS spectra were analysed by MaxQuant, followed by statistical analyses employing Perseus and, functional annotation and pathway analyses with Ingenuity Pathway Analysis.

Results : Ang II elicited an acute differential expression of 312 and 34 proteins in the R and OA, respectively. Comparative protein expression analysis revealed that protein clusters involved in actin cytoskeleton and integrin-linked kinase signaling were significantly activated in the OA as part of the ocular vascular adaptation processes and, could be one measure to cope with oxidative stress. Conversely, a large majority of differentially expressed R proteins were involved in mitochondrial dysfunction (p=1.15E-24), inhibition of oxidative phosphorylation (p=2.00E-22) and, eukaryotic initiation factor 2 signalling, which is crucial for cell survival and is increasingly implicated in the pathogenesis of neurodegenerative diseases due to aberrant translational machinery in the cell.

Conclusions : These findings corroborate with our hypothesis that the OA has inherent capacity to maintain cellular redox balance, whereas the R is highly susceptible to oxidative damage as evidenced by the inactivation of potential neuroprotective mechanisms. In gist, we provide the first in-depth insight into the key molecular and functional changes associated with acute adaptive response to oxidative stress in R compared to a retrobulbar vascular bed.

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

 

In-house vascular protein extraction workflow

In-house vascular protein extraction workflow

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