HomeScience and ResearchScientific ResearchEye Color Genes Reveal Critical Link To Retinal Health

Eye Color Genes Reveal Critical Link To Retinal Health

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Metabolic pathways involve a sequence of biochemical reactions within cells that transform a starting component into other substances. Evidence is mounting that these pathways, in conjunction with external stress factors, can impact the well-being of cells and tissues.

The kynurenine pathway is a metabolic pathway that has been conserved through evolution and controls various biological processes.

This metabolic pathway converts the amino acid tryptophan into other products through a series of steps. The study conducted by the researchers focused on the role of this pathway in maintaining retinal health, separate from its function in pigment formation.

This pathway is highly conserved across evolution and regulates many biological processes. Its disruption can result in the buildup of either toxic or protective biomolecules or metabolites, which can negatively or positively impact brain health, including the retina.

Elisabeth Knust, Director Emerita at the MPI-CBG, and her team recently expanded our understanding of this crucial metabolic pathway. They published their findings in the journal Plos Genetics.

Given the pathway’s significant conservation and the genes that control it, the team used flies as a model system to investigate the impact of individual metabolites on retinal health. They focused on four genes – cinnabar, cardinal, white, and scarlet – named after the abnormal eye colors observed in flies following their loss.

“Since the Kynurenine pathway is conserved from flies to humans, we asked whether these genes regulate retinal health independent of their role in pigment formation,” adds lead author Sarita Hebbar.

To investigate further, the scientists utilized genetics, dietary modifications, and biochemical analysis of metabolites in various mutations of the fruit fly, Drosophila melanogaster.

One of the co-authors, Sofia Traikov, developed a technique to analyze the metabolites of the kynurenine pathway, which allowed the researchers to associate different metabolite levels with the retinal health status.

The team discovered that 3-hydroxykynurenine (3OH-K), a particular metabolite, is detrimental to the retina. More crucially, they were able to demonstrate that the extent of degeneration is influenced by the balance between toxic 3OH-K and protective metabolites, such as Kynurenic Acid (KYNA), rather than their absolute quantities.

“We also fed two of these metabolites to normal (non-mutant) flies and found that 3OH-K enhanced stress-induced retinal damage, whereas KYNA protected the retina from stress-related damage.” adds Sarita.

The findings suggest that the ratio of metabolites in the kynurenine pathway can be adjusted to enhance retinal health in specific circumstances.

Moreover, the researchers were able to illustrate that by targeting the four genes responsible for the four distinct steps within the pathway, not only the accumulation of 3OH-K but also its location within the cell and subsequent availability in further reactions are significant for retinal health.

“This work shows that the Kynurenine pathway is important not only in pigment formation but that the level of individual metabolites fulfills important roles in maintaining retinal health,” adds Elisabeth Knust, who supervised the study.

She further adds, “In the future, the ratio of the various metabolites and the specific sites of their accumulation and activity should be taken into account in therapeutic strategies for diseases with impaired Kynurenine pathway function, observed in various neurodegenerative conditions.”

Image Credit: Getty

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