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Accelerated aging induced by stress in experimental murine ocular hypertension

Qianlan Xu, Cezary Rydz, Viet Anh Nguyen Huu, Lorena Rocha, Claudia Palomino La Torre, Irene Lee, William Cho, Mary Jabari, John Donello, Robert N. Weinreb, David C. Lyon, Won-Kyu Ju, Andrzej Foik, View ORCID ProfileDorota Skowronska-Krawczyk
doi: https://doi.org/10.1101/2022.05.01.490248
Qianlan Xu
1Department of Physiology and Biophysics, Center for Translational Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
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Cezary Rydz
1Department of Physiology and Biophysics, Center for Translational Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
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Viet Anh Nguyen Huu
2Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, School of Medicine, University of California, San Diego, La Jolla, CA
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Lorena Rocha
2Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, School of Medicine, University of California, San Diego, La Jolla, CA
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Claudia Palomino La Torre
2Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, School of Medicine, University of California, San Diego, La Jolla, CA
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Irene Lee
1Department of Physiology and Biophysics, Center for Translational Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
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William Cho
1Department of Physiology and Biophysics, Center for Translational Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
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Mary Jabari
2Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, School of Medicine, University of California, San Diego, La Jolla, CA
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John Donello
1Department of Physiology and Biophysics, Center for Translational Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
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Robert N. Weinreb
2Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, School of Medicine, University of California, San Diego, La Jolla, CA
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David C. Lyon
3Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA
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Won-Kyu Ju
2Viterbi Family Department of Ophthalmology, Hamilton Glaucoma Center and Shiley Eye Institute, School of Medicine, University of California, San Diego, La Jolla, CA
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Andrzej Foik
3Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA
4International Centre for Translational Eye Research, Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland
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Dorota Skowronska-Krawczyk
5Department of Physiology and Biophysics, Department of Ophthalmology, Center for Translational Vision Research, School of Medicine, University of California, Irvine, Irvine, CA
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  • ORCID record for Dorota Skowronska-Krawczyk
  • For correspondence: dorotask@hs.uci.edu
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ABSTRACT

Aging, a universal process that affects all cells in an organism, is a major risk factor for a group of neuropathies called glaucoma, where elevated intraocular pressure is one of the known stresses affecting the tissue. Our understanding of molecular impact of aging on response to stress in retina is very limited, therefore we developed a new mouse model to approach this question experimentally. Here we show that susceptibility to response to stress increases with age and is primed on epigenetic level. We demonstrate that program activated by hypertension is similar to natural aging, and that one of the earliest pathways activated upon stress is senescence. Finally, we show that multiple instances of pressure elevation cause accelerated aging of young retina as measured on transcriptional and epigenetic level. Our work emphasizes the importance of early diagnosis and prevention as well as age-specific management of age-related eye-diseases, including glaucoma.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Conversion to pdf erased some symbols on figures. Current version has all symbols and annotations.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 05, 2022.
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Accelerated aging induced by stress in experimental murine ocular hypertension
Qianlan Xu, Cezary Rydz, Viet Anh Nguyen Huu, Lorena Rocha, Claudia Palomino La Torre, Irene Lee, William Cho, Mary Jabari, John Donello, Robert N. Weinreb, David C. Lyon, Won-Kyu Ju, Andrzej Foik, Dorota Skowronska-Krawczyk
bioRxiv 2022.05.01.490248; doi: https://doi.org/10.1101/2022.05.01.490248
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Accelerated aging induced by stress in experimental murine ocular hypertension
Qianlan Xu, Cezary Rydz, Viet Anh Nguyen Huu, Lorena Rocha, Claudia Palomino La Torre, Irene Lee, William Cho, Mary Jabari, John Donello, Robert N. Weinreb, David C. Lyon, Won-Kyu Ju, Andrzej Foik, Dorota Skowronska-Krawczyk
bioRxiv 2022.05.01.490248; doi: https://doi.org/10.1101/2022.05.01.490248

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