A recent study conducted by researchers from the University of Barcelona has shed light on how the absence of the CERKL gene affects the ability of retinal cells to combat oxidative stress caused by light, leading to cell death and blindness. The study, published in the journal Redox Biology, provides valuable insights into the mechanisms underlying hereditary blindness and paves the way for future precision medicine-based treatments.
Led by Professor Gemma Marfany, the study involved the collaboration of teams from the University of Valencia, Sant Joan de Déu Research Institute, Severo Ochoa Molecular Biology Center, and Hospital 12 de Octubre Research Institute. By using animal models, the researchers discovered that the lack of the CERKL gene results in a state of permanent stress in retinal cells. This leaves the cells unable to activate antioxidant response mechanisms when subjected to additional oxidative damage caused by light stimulation, leading to chronic inflammation and cell death.
The study also revealed that the absence of the CERKL gene triggers cell death mechanisms such as necroptosis and ferroptosis, offering an explanation for the progressive degeneration of photoreceptor cells observed in patients with CERKL mutations. Although the experiments were conducted on mice, the findings have important implications for understanding the pathogenesis of hereditary vision diseases in humans.
The researchers investigated how the retina responds to light when the CERKL gene is missing using a transgenic mouse model. They found that the retina degenerated progressively, mirroring the degeneration seen in human patients. The study combined various approaches, including transcriptomics and metabolomic analysis, to understand how the retina copes with oxidative damage when the CERKL protein is absent.
Further research is needed to fully understand the function of the CERKL gene and devise targeted therapies. The identification of the CERKL gene and its physiological function are essential for the development of precision therapies, including gene therapy and the use of drugs to restore the proper functioning of retinal neurons. These approaches could slow down the progression of hereditary vision diseases and benefit a larger number of patients.
Hereditary retinal dystrophy affects approximately 1 in 3,000 people worldwide, making it one of the most prevalent rare diseases. While 90 genes associated with retinitis pigmentosa have been identified, over 300 genes can potentially impact vision. The ability to accurately diagnose the gene causing the disease and understand its physiological effect are crucial steps in the design of personalized therapies.
The research conducted by the University of Barcelona is part of ongoing efforts to unravel the mysteries of hereditary vision diseases. With a focus on understanding how mutations in the CERKL gene contribute to photoreceptor death, the team aims to develop new models of the disease using human retinal organoids. Ultimately, their goal is to design precision therapies that can reverse the most severe symptoms of retinitis pigmentosa.
(Source: University of Barcelona)