Elucidating and exploiting inhibitory memories to treat drug addiction
02 / 2009 - 02 / 2015
Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly population. A clinical hallmark of AMD is the development of small white-yellow deposits, called drusen, in the macula. AMD is a multifactorial disorder caused by genetic and environmental influences. A major breakthrough in the AMD field was the identification of strong association with variants in the complement factor H (CFH) gene. Variants in CFH, in two other complement factor genes, and in a gene encoding a mitochondrial protein, account for ~50% of the genetic risk factors for AMD. This proposal aims to unravel the remaining genetic risk factors for AMD. I will use a new endophenotype-based approach by focussing on genes involved in drusen formation. Basal laminar drusen represent a specific subtype of drusen that are found in AMD patients, but can also develop as a separate entity in young adults. Very recently we showed that this entity, in a subset of patients, can be caused by recessive inheritance of CFH variants. This exciting discovery indicates that the basal laminar drusen phenotype is easier to dissect by genetic studies than the more complex disease AMD. In this study we will analyse the role of the complement cascade and perform genome-wide linkage studies in families with basal laminar drusen. This will allow us to dissect new pathways and mechanisms that are involved in drusen formation. Variants in these new genes will then be analysed for their involvement in AMD. By identifying new genes involved in AMD, I expect that the majority of AMD cases can be predicted by diagnostic genotyping tests in the near future. Individuals who are at high risk to develop AMD can be advised nutrient-based interventions. Ultimately, discovery of new biomarkers will provide new targets for the development of therapeutic strategies for AMD.
Maculadegeneratie is de voornaamste oorzaak van slechtziendheid bij ouderen. De onderzoekers zullen op zoek gaan naar erfelijke factoren (genen) die deze vorm van slechtziendheid veroorzaken. Hiermee zullen ze het ontstaan van deze ziekte beter begrijpen, en mogelijk nieuwe aangrijpingspunten voor therapie ontdekken.