Stem Cells Lead to Better Understanding of Retinal Development


Immunostaining of a developing neuroretina (red) surrounding the lens (nuclei in yellow). F-actin-expressing cells are in green.

Northwestern Medicine scientists used embryonic stem cells and induced pluripotent stem cells to generate eye organoids that mimic early eye development, creating a tool that allowed them to characterize molecular events that regulate the formation of the complex organ. The findings were published in Cell Reports.

The scientists focused on the neuroretina, a collection of eye cells that help convert light into neural signals, and identified the gene Rspondin-2 as a critical player in mammalian neuroretina differentiation.

The authors found that during early development, when the eye is initially forming and is still just an outgrowth of neural tissue, the activity of the transcription factor Six3 is required to repress Rspondin-2 from the anterior part of the head where the eyes are eventually going to form.

“The prospect of using stem cell-based therapies to treat different types of retinal diseases is becoming a real possibility; therefore, having a better understanding of the cellular and molecular processes controlling eye morphogenesis and neuroretina differentiation is critical,” said principal investigator Guillermo Oliver, PhD, the Thomas D. Spies Professor of Lymphatic Metabolism. Nozomu Takata, PhD, a postdoctoral fellow in Oliver’s lab, was the first author.

The study also showed that stem cells can accurately recreate live organs in lab-grown models, opening up possibilities for future research.

“Our results further validate the organoid culture system as a reliable and fast alternative to identify and evaluate genes involved in eye morphogenesis and neuroretina differentiation in vivo,” said Oliver, a professor of Medicine in the Division of Nephrology and Hypertension, and the director of the Center for Vascular and Developmental Biology at the Feinberg Cardiovascular Research Institute.

This work was supported by the National Eye Institute grant EY12162 and a Fellowship for Research Abroad from the Uehara Memorial Foundation.