Mutated CRB1 in human induced pluripotent stem cell derived retinal organoids

PI: Stefan Liebau and Marius Ueffing

Institution:  Eberhard Karls University Tuebingen, Institute of Neuroanatomy

MDBR Statistics

Institutions Awarded

47

Countries Awarded

11

# of Awards

106

Total Amount

$6,405,314

One of the factors involved in an inherited, early onset and severe form of retinal degeneration is the “Crumbs Homolog 1” (CRB1). Crumbs, the homologue of the vertebrate gene CRB1 has originally been found in the fruit fly “Drosophila melanogaster” where it has been described to take part in the molecular scaffold being responsible for proper eye polarity. Our knowledge of the function CRB1 in the human organism and its role in the disease leading to a loss of photoreceptors is still underdeveloped. The presented study is designed to gain further insights into the pathomechanism of CRB1-related hereditary retinal diseases.

For that we investigate patient specific 3-dimensional organ like structures (organoids) that we generate from induced pluripotent stem cells derived from plucked human hair keratinocytes. These organoids show a cell diversity and layering in close proximity to the situation in the human physiological retina. Using several experimental approaches, we will take a close look into the molecular biology of retinal cell populations with a focus on the expression and function of CRB1. In subsequent experiments we will try to rescue the pathomechanisms with pharmacological intervention of signaling cues involved in the disease onset and progression.