Related Experiment Video
Updated: Jun 15, 2025
07:48
Glutamate and Hypoxia as a Stress Model for the Isolated Perfused Vertebrate Retina
Published on: March 22, 2015
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Serine and glycine physiology reversibly modulate retinal and peripheral nerve function
Esther W Lim1, Regis J Fallon2, Caleb Bates2
1Molecular and Cellular Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA; Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.
Cell Metabolism
|August 27, 2024
Summary
Metabolic pathways involving serine, glycine, and one-carbon (SGOC) are crucial for eye health. Supplementing serine can reverse retinal and nerve damage in mouse models, offering therapeutic potential for neuro-retinal diseases.
Area of Science:
- Biochemistry
- Metabolic pathways
- Neuroscience
Background:
- Metabolic homeostasis relies on redundant pathways for nutrient supply during stress.
- These pathways are regulated locally in tissues and systemically by organs like the liver and kidneys.
- Serine, glycine, and one-carbon (SGOC) metabolism is vital for maintaining amino acid levels and function in the retina.
Purpose of the Study:
- To characterize the role of SGOC metabolism in sustaining retinal amino acid levels and function.
- To investigate the impact of SGOC metabolic enzyme haploinsufficiency on retinal health.
- To explore therapeutic interventions for SGOC metabolism-related neuro-retinal dysfunction.
Main Methods:
- Analysis of SGOC metabolism fluxes across the eye, liver, and kidney.
- Utilizing a Phgdh+/- mouse model with SGOC metabolic enzyme haploinsufficiency.
- Assessing retinal defects and neuropathy in response to dietary serine/glycine restriction and serine supplementation.
Main Results:
- Individuals with Macular Telangiectasia (MacTel) show reduced circulating serine and glycine, with deleterious alleles in SGOC metabolic enzymes.
- Phgdh+/- mice exhibit accelerated retinal defects upon dietary serine/glycine restriction.
- Serine supplementation reversed serine-associated retinopathy and peripheral neuropathy in mice.
Conclusions:
- SGOC metabolism is critical for maintaining retinal amino acid levels and function.
- Silent haploinsufficiencies in SGOC metabolic enzymes can exacerbate retinal defects, particularly under dietary stress.
- Serine supplementation represents a viable therapeutic strategy for reversing neuro-retinal dysfunction caused by SGOC metabolism defects.
Keywords:
MacTelPHGDHglycineglycine cleavageone-carbon metabolismretina metabolismserineserine supplementationsphingolipidsstable-isotope tracingMore Related Videos
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