A team led by biochemists Karl-Wilhelm Koch and Farina Vocke has succeeded in elucidating the molecular basis of a genetic retinal disease. The findings could help to better understand more common forms of retinal degeneration.
No longer seeing clearly, problems reading or difficulties recognising people you know on the street: Older people in particular can suffer from so-called age-related macular degeneration. This retinal disease affects the area of sharpest vision in the eye - the macula, also known as the yellow spot. As the disease progresses, the field of vision becomes increasingly restricted and, in the worst case, those affected can go blind. However, the causes of this disease are complex - various genetic and non-genetic factors play a role here - and treatment is not easy.
In order to track down the causes of this disease, scientists are also investigating diseases with similar symptoms, such as macular dystrophy. "The symptoms - especially the increasing loss of vision in the central visual field - are very similar in both diseases," says Prof Dr Karl-Wilhelm Koch from the Department for Neuroscience. However, the causes are less complex: "The disease can be traced back to a so-called point mutation, i.e. a single altered gene," adds the biochemist.
Together with his doctoral student Farina Vocke and an international team of human geneticists and biophysicists from Tübingen, Verona (Italy) and Philadelphia (USA), Koch has now succeeded in identifying the altered gene and analysing it in more detail. The results have been published in the renowned scientific journal Human Molecular Genetics.
The research team first analysed the genetic material of affected patients. They were able to identify the mutated gene, which also occurs in families in which the disease is clearly inherited. The affected gene contains the blueprint for a protein that is found in the cells of the retina and controls important messenger substances.
The scientists then used various analytical methods to create a so-called molecular fingerprint of the disease. This means that they analysed various properties of the defective protein in comparison to the healthy variant and the consequences that result from the malfunction. For example, the light-regulated messenger cyclo-GMP is produced significantly more in the affected cells under physiological, i.e. natural, conditions. This significantly disrupts cell function.
The researchers suspect that such malfunctions contribute to age-related macular degeneration in a similar way. Despite the significantly more complex relationships, Koch believes that the results could help to understand how this disease develops. So far, researchers have found genetic changes in more than 200 genes that cause retinal diseases. "However, the exact molecular and cellular consequences of these mutations are only known in a few cases," adds the biochemist.