New mechanisms causing blindness in mouse models discovered
A multidisciplinary research team, under the leadership of geneticist Gemma Marfany, has recently published an article in the journal Redox Biology. Their study, conducted using a mouse model, reveals that the absence of the CERKL gene (associated with hereditary vision disorders) impairs the retina's capacity to withstand oxidative stress induced by light exposure. This chemical imbalance can ultimately lead to the death of retinal cells, ultimately resulting in blindness.
The CERKL gene, therefore, plays a crucial "protective" role against oxidative stress within the retina. Cells in this delicate tissue are constantly exposed to light, which disrupts their balance of reactive oxygen species, highly oxidising molecules that can generate oxidative stress. To prevent the excessive production of these molecules from causing harm to cells, they possess protective mechanisms, such as the one initiated by CERKL. In their research, the team used an albino mouse model lacking this gene and subjected it to light radiation to observe how the chemical equilibrium of the retina was affected. They observed that the retina remained in a state of chronic inflammation. In situations of inflammation, cells activate mechanisms that lead to cell death. As explained by Marfany, the study's leader: "While these experiments were conducted in mice, these findings shed light on how and why photoreceptor cells die in patients, resulting in blindness. This knowledge complements genetic research and opens up promising avenues for future therapeutic approaches."
The researcher also underscores the importance of genetic diagnosis and comprehending the functions of the genes implicated in the disease, as these are pivotal in devising personalised therapies. She states, "With a deeper insight into the pathways that become disrupted in the absence of the CERKL gene, we can explore potential compensatory strategies. This might include the use of drugs that target these metabolic pathways to restore the normal functioning of retinal neurons."
Hereditary retinal dystrophies impact approximately one in every 3,000 individuals across the globe. To date, researchers have identified 90 genes associated with retinitis pigmentosa, and approximately 3% of patients in Spain carry mutations in the CERKL gene.
*Original source: Descubiertos nuevos mecanismos que provocan ceguera y abren la puerta a nuevos tratamientos
