More than meets the eye A translational approach to gyrate atrophy of the choroid and retina

In this thesis, a translational approach is used to gather more insight into gyrate atrophy of the choroid and retina (GACR), an inherited metabolic disorder which leads to severe visual impairment and blindness. Both from a clinical and translational perspective, this thesis provides novel insights into clinical phenotype, treatment effects, diagnostic tools, and pathophysiological mechanisms, while also providing a thorough review of current literature.
The first part of the thesis covers existing knowledge on GACR and provides a comprehensive overview of previously described and currently applied treatments. In the second part, we learn from the persons living with this disease: in two cohort studies both the ophthalmic phenotype as well as the systemic phenotype of the disease is thoroughly analysed. Furthermore, we develop a novel diagnostic assay to allow for improved clinical management. In the third part, we look at the future, analysing target organs for molecular therapy and using a multi-omics approach to identify possible novel therapeutic targets.
The framework used for the research included in this thesis can be applied to other forms of metabolic blindness, i.e. blindness caused by inherited metabolic disorders, and the disease-specific insights provide a foundation for the development of novel therapeutic interventions for this rare and devastating disease.