Elucidating the molecular mechanisms underlying CRB1-related Leber congenital amaurosis (LCA)

Patients with genetic mutations in the CRB1 gene have varied clinical features and levels of disease severity ranging from Leber congenital amaurosis (LCA), early onset retinal dystrophy (EORD) to retinitis pigmentosa (RP). The relationship between genetic mutation and clinical presentation is not well understood. Our lab have characterised two disease models of CRB1 (Owen et al 2023); zebrafish and patient grown stem cell derived early retinas. Investigation reveals lack of the CRB1 protein prevents the retina from developing into a mature state with precise defined cell types, instead it is locked in an early stage of development with lots of cells dividing. To futher understand the underlying molecular mechanisms causing the CRB1 phenotype we have carried out transcriptome analysis of iPSC derived 3D retinal organoids at day 35.