Rod photoreceptor-specific knockout of glutaminase (GLS) shows speedy retinal degeneration and elevated markers of cell demise. Credit score: eLife (2025). DOI: 10.7554/eLife.100747.3
The retina locations a big power demand on the physique, partly as a result of exercise of photoreceptors.
These specialised cells are chargeable for receiving gentle and transmitting visible data to the mind.
Photoreceptor demise is the reason for imaginative and prescient loss in lots of retinal illnesses, and there are not any efficient therapies that enhance their survival.
In a paper printed in eLife, College of Michigan researchers studied the dependence of photoreceptors on glutamine. Their outcomes point out that sustaining the steadiness of amino acids in these cells is essential for photoreceptor well being.
The power necessities of photoreceptors make them weak to small adjustments in metabolism. Earlier research targeted on glucose as the first gasoline supply for these cells.
At present, a remedy that exploits photoreceptor dependence on glucose is being examined in a medical trial for sufferers with retinal degeneration.
“Photoreceptors are one of the most metabolically demanding cells in the body, which led us to wonder whether they depend on fuel sources other than glucose for their survival,” mentioned Thomas Wubben, M.D., Ph.D., assistant professor of ophthalmology and visible sciences. “We looked at glutamine because it is the most abundant amino acid in the blood.”
Glutamine feeds into a number of pathways, serving to cells construct different amino acids, together with glutamate and aspartate, protein and DNA.
To verify glutamine’s function in imaginative and prescient, the researchers used mice that lacked the enzyme glutaminase, which breaks down glutamine into glutamate. They in contrast these mice to manage mice by measuring the thickness of their retinas. Mice that lacked glutaminase had a speedy discount in retinal thickness with lack of photoreceptor quantity and performance.
Glutamine performs a job in a number of mobile processes. To know why glutamine is essential to photoreceptor survival, the workforce measured the degrees of various molecules in management mice and those who lacked glutaminase.
When mice lacked the enzyme, they’d decrease ranges of glutamate and aspartate. These amino acids, in flip, assist the cells construct proteins which are required for photoreceptor perform.
The researchers additionally discovered that decreased amino acid ranges activated the built-in stress response, which is thought to set off cell demise if it stays lively for too lengthy. After they inhibited the stress response, the workforce discovered that the retinal thickness elevated.
“We are now focused on understanding which pathways depend on glutamine and whether they can be targeted by drugs or supplements,” Wubben mentioned.
Glutamine to glutamate conversion pathways are negatively impacted in fashions of human retinal illness.
“It is possible that resetting metabolism can help prevent vision loss and blindness.”
Extra data:
Moloy T Goswami et al, Glutamine catabolism helps amino acid biosynthesis and suppresses the built-in stress response to advertise photoreceptor survival, eLife (2025). DOI: 10.7554/eLife.100747.3
Journal data:
eLife
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College of Michigan
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Amino acid glutamine is essential for eye well being, analysis finds (2025, August 4)
retrieved 4 August 2025
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