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

---

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.

Targeting retinoid traffic for treatment of CRB1-CRUMB1 degenerative retinal disorders

Awardee: Konstantin Petrukhin

Institution: Columbia University Medical Center

Grant Amount: $44,037

Characterisation of CRB1 patient human iPSC-derived retinal organoids to set-up potency assays for gene therapy

Awardee: Jan Wijnholds

Institution: Leiden University Medical

Award Amount: $40,177

AAV gene therapy on cultured human iPSC-derived retina with loss of CRB1 and CRB2

Awardee: Jan Winjholds

Institution: Leiden University Medical Center (LUMC)

Award Amount: $50,312

Funding Period: February 1, 2019 - January 31, 2020

CRB1-null human retinal organoids for disease modeling and gene therapy testing

Awardee: Wei Liu

Institution: Albert Einstein College of Medicine

Award Amount: $50,312

Funding Period: February 1, 2019 - January 31, 2020

Functional dissection of CRB1 homophilic interactions in Retinitis pigmentosa

Awardee: Toby Hurd

Institution: University of Edinburgh

Award Amount: $50,497

Funding Period: January 1, 2018 - December 31, 2018

Establishing 3-Dimensional (3D) Retinal Optic Cups using patient-specific CRB1 Induced Pluripotent Stem Cells.

Awardee: Jason Mills

Institution: University of Pennsylvania

Award Amount: $50,500

Funding Period: January 1, 2017 - December 31, 2017

Mutated CRB1 in human induced pluripotent stem cell derived retinal organoids

Awardee: Stefan Liebau & Marius Ueffing

Institution: Eberhard Karls University Tuebingen, Institute of Neuroanatomy

Award Amount: $50,500

Funding Period: January 1, 2017 - December 31, 2017