Using human retinal organoids to discover mechanisms and therapies for CRB1 retinopathy

Awardee: Brian Ballios

Institution: University Health Network

Grant Amount: $66,991

Funding Period: February 1, 2025 - January 31, 2026

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Summary:

Mutations in the CRB1 gene cause early cellular disorganization of the retina and loss of the light-sensitive photoreceptors in the eye, leading to irreversible blindness in children and adolescents. No treatments exist for these diseases. Structural differences between rodent and human retinal tissue preclude the use of animal models to uncover new therapies. Our work uses human CRB1 patient-derived stem cells to generate retinal “mini-organs in a dish” (organoids) to model CRB1 disease in the lab. Retinal organoids exhibit the same structure and major cell types found in the human retina; our CRB1 retinal organoids have the exact genetic makeup as the patient they were derived from. Comparisons of early retinal development in our CRB1 organoids with those derived from a healthy donor have shown defects in cell birth and proliferation. We aim to characterize how these early abnormalities affect the mature structure and organization of the retina in older organoids. We will analyse gene expression differences between healthy and CRB1-diseased organoids to uncover mechanisms and pathways involved in causing the disease state. These will serve as targets for testing new therapies for CRB1 disease using drugs known to modulate those pathways, and observe whether we can reverse early developmental defects.