Human macular Müller cells rely more on serine biosynthesis to combat oxidative stress than those from the periphery
- The University of Sydney, Australia
- Sidra Medicine, Qatar
- St Vincent's Hospital, Australia
- West Virginia University, United States
Abstract
The human macula is more susceptible than the peripheral retina to developing blinding conditions such as age-related macular degeneration, diabetic retinopathy. A key difference between them may be the nature of their Müller cells. We found primary cultured Müller cells from macula and peripheral retina display significant morphological and transcriptomic differences. Macular Müller cells expressed more Phosphoglycerate Dehydrogenase (PHGDH, a rate-limiting enzyme in serine synthesis) than peripheral Müller cells. The serine synthesis, glycolytic and mitochondrial function were more activated in macular than peripheral Müller cells. Serine biosynthesis is critical in defending against oxidative stress. Intracellular reactive oxygen species and glutathione levels were increased in primary cultured macular Müller cells which were more susceptible to oxidative stress after inhibition of PHGDH. Our findings indicate serine biosynthesis is a critical part of the macular defence against oxidative stress and suggest dysregulation of this pathway as a potential cause of macular pathology.
Data availability
RNA sequencing data are included in the manuscript and Supplementary File. These data are also available at Dryad (https://datadryad.org/dx.doi:10.5061/dryad.hp60p89)
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Data from: Human macular Müller cells rely more on serine biosynthesis to combat oxidative stress than those from the peripheryDryad Digital Repository, 10.5061/dryad.hp60p89.
Article and author information
Author details
Funding
National Health and Medical Research Council
- Ling Zhu
- Weiyong Shen
- Mark Cedric Gillies
The Ophthalmic Research Institute of Australia
- Ling Zhu
- Mark Cedric Gillies
National Institutes of Health
- Jianhai Du
Lowy Medical Research Institute
- Ting Zhang
- Ling Zhu
- Weiyong Shen
- Mark Cedric Gillies
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Human retinas were obtained from post-mortem donor eyes with ethical approval from Human Research Ethics Committee of the University of Sydney (HREC#:16/282).
Copyright
© 2019, Zhang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Human macular Müller cells rely more on serine biosynthesis to combat oxidative stress than those from the periphery
eLife 8:e43598.
https://doi.org/10.7554/eLife.43598
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