A new study finds that the genes that control eye colour have a relationship with the health of retina. This relates, initially to studies in fruit flies although the research is considered to be extrapolatable to humans. Here, a research team has demonstrated how four Drosophila genes, known to control eye colour, are essential for health of retinal tissue.
Researchers from the Max Planck Institute of Molecular Cell Biology and Genetics have identified that metabolic pathways consist of a series of biochemical reactions in cells that convert a starting component into other products. From this, they provided research that adds to the growing evidence that metabolic pathways coupled with external stress factors influence the health of cells and tissues.
From this, it is reasoned that any human diseases, including retinal or neurodegenerative diseases, are associated with imbalances in metabolic pathways. Therefore, there is growing evidence that metabolic pathways coupled with external stress factors influence the health of cells and tissues.
The implications of the study are such that many human diseases, including retinal or neurodegenerative diseases, appear to be associated with imbalances in metabolic pathways. Focusing on these pathways could provide a new array of treatments.
For the study, the research team studied the classic Drosophila genes cinnabar, cardinal, white, and scarlet (named due to their role in eye colour pigmentation, in particular the formation of the brown pigment of the fly eye). The importance of these genes is because they encode components of the kynurenine pathway, whose activity converts the amino acid tryptophan by various steps into other products.
In the new study, the scientists highlighted the function of this metabolic pathway in retinal health, independent of its role in pigment formation.
The Kynurenine pathway is an evolutionary conserved metabolic pathway that regulates a variety of biological processes. Its disruption can result in the build-up of either toxic or protective biomolecules or metabolites, which can worsen or improve, respectively, the health of the brain, including the retina.
Furthermore, the scientists have identified how knowledge on this important metabolic pathway and the genes that regulate it can help to unravel the role of individual metabolites in retinal health.
By deploying a combination of genetics, dietary changes, and biochemical analysis of metabolites ,the researchers successfully detailed the different mutations of the fruit fly, Drosophila melanogaster.
This allowed the researchers to link different metabolite levels to the health state of the retina. They found that one metabolite, 3-hydroxykynurenine (3OH-K), is damaging to the retina. More importantly, they could show that the degree of degeneration is influenced by the balance between toxic 3OH-K and protective metabolites, such as Kynurenic Acid (KYNA), and not just by their absolute amounts.
By targeting these four genes and therefore four distinct steps within the pathway, the scientists were able to show that not only the accumulation of 3OH-K as such, but also its location in the cell and hence its availability in further reactions, is important for retinal health.
The research appears in the journal PLOS Genetics, titled “Modulating the Kynurenine pathway or sequestering toxic 3-hydroxykynurenine protects the retina from light-induced damage in Drosophila.”
