A team of researchers led by Elisabeth Knust at Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) in Dresden, Germany investigated how four Drosophila genes, known to control eye colour, are important for the health of retinal tissue.
In cells, metabolic pathways consist of a series of biochemical reactions that convert a starting component into other products. There is mounting evidence that these pathways along with external stress factors influence the health of cells and tissues, according to a recent article on the MPI-CBG website. Human diseases such as retinal or neurodegenerative diseases are linked to imbalances in metabolic pathways.
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The study conducted by MPI-CBG researchers examined the classic Drosophila genes cinnabar, cardinal, white, and scarlet, named due to their role in eye colour pigmentation and specifically, the formation of the brown pigment of the fly eye, according to Press Trust of Inida.
These genes have components of the Kynurenine pathway, a metabolic pathway responsible for regulating eye colour. Any disruption in these genes can result in the build-up of either toxic or protective biomolecules or metabolites, which could impact the health of the brain, including the retina. “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,” said Sarita Hebbar, one of the lead authors of the study in the article.
The researchers used a combination of genetics, dietary changes, and biochemical analysis of metabolites to examine different mutations of the fruit fly. A method for the biochemical analysis of the metabolites in the Kynurenine pathway, developed by Sofia Traikov, enabled the linking of different metabolite levels to the retina’s health state. They found that a metabolite, 3-hydroxykynurenine (3OH-K) is damaging to the retina. The also showed that the degree of degeneration is influenced by the balance between toxic metabolites and the protective ones such as Kynurenic Acid (KYNA), according to the article.
The study demonstrated that retinal health can be improved by altering the ratio of metabolites of the Kynurenine pathway. The researchers also showed that the metabolites’ location and their availability for further reactions, are important for retinal health. "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," said Knust in the article.
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