Mainly based on long-term cultivated retinal organoids derived from hiPSCs, this project attempts to generate knowledge and provide candidate targets for interventional cell based as well as molecular therapy of patients suffering from CRB1 associated retinal degeneration. In the search for understanding the pathomechanisms behind this form of RD, we attempt to develop tools that allow assessment of molecular defects caused by mutation. Given that we and others do see variant disease severity in patients, we will specifically look for modifiers of disease and mechanisms for protection. This requires a holistic view on the role of CRB1 within retinal development, which we will attempt to gain by combining a deep mutli-omics approach in combination with advanced bioinformatics and computational modelling.