A recent study conducted by the University of Barcelona has shed light on the role of the CERKL gene in hereditary vision diseases such as retinitis pigmentosa. The research team discovered that the absence of the CERKL gene affects the retina’s ability to combat oxidative stress generated by light, leading to cell death mechanisms that ultimately cause blindness.
Published in the journal Redox Biology, the study has provided valuable insights into the mechanisms underlying hereditary blindness, which can inform future precision medicine-based treatments. Professor Gemma Marfany, leader of the study, collaborated with teams from the Sant Joan de Déu Research Institute, University of Valencia, Severo Ochoa Molecular Biology Center, and the Hospital 12 de Octubre Research Institute.
The research utilized animal models and revealed that the lack of the CERKL gene results in a state of constant stress in retinal cells. In the absence of this gene, the cells are unable to activate antioxidant response mechanisms, leaving them unable to respond to additional oxidative damage caused by continuous light stimulation. Consequently, the retina becomes chronically inflamed, leading to the activation of cell death mechanisms like necroptosis and ferroptosis. These findings provide an explanation for the death of photoreceptor cells in patients with hereditary vision diseases.
The study also investigated how the retina responds to light when the CERKL gene is missing. By using a transgenic mouse model, the researchers demonstrated that the retina progressively degenerates, mirroring the degeneration seen in human patients. The team utilized various approaches, including transcriptomics and metabolomic analysis, to understand the pathology caused by CERKL mutations.
With 90 identified genes associated with retinitis pigmentosa and over 300 genes that can impact vision, identifying the specific gene causing a disease is crucial for effective treatments. According to Marfany, approximately 3% of retinitis pigmentosa patients in Spain have mutations in the CERKL gene. Therefore, genetic diagnosis and understanding the physiological effects of mutations are essential steps towards developing therapeutic approaches for patients with hereditary vision diseases.
Sources:
– The study by the University of Barcelona reveals how the lack of the CERKL gene, which causes hereditary vision diseases, is capable of altering the retina’s ability to fight oxidative stress and cause blindness. (Redox Biology, 2023)
– DOI: 10.1016/j.redox.2023.102862
