Generating eye tissue for research and treatment
- Type of funding: Project Grant
- Grant Holder: Prof Shin-ichi Ohnuma
- Institute: UCL Institute of Ophthalmology
- Region: London
- Start date: June 2016
- End Date: May 2019
- Priority: Treatment
- Eye Category: AMD
It would be very useful if researchers could reliably produce working eye tissue - or even whole eyes - from stem cells. The tissue could be used for transplants to treat people with sight loss or to test new drugs.
But the eye is a very complex organ made up of several different types of tissue including the lens, cornea and retina. There are 7 major types of nerve cells and it all has to be connected in the right way. At the moment there is no good way to generate a whole eye system outside of a living creature.
The research team has recently discovered a protein that can cause eye tissue to develop in frog embryos, and so it has the potential to benefit research and treatment. But the protein hasn’t been studied yet.
In the current project the team aims first to understand how it triggers eye tissue development. Then they will try to improve the method for generating both eye tissue and whole eyes from human stem cells. As well as improving treatments, the results could help to reduce the number of animal experiments needed for medical research into sight loss.
Optimisation of organised eye production from Xenopus and human stem cells by a defined factor
Generation of eye tissue from stem cells in vitro has an immediate clinical application in providing tissue for transplantation together with an immediate application for drug discovery by allowing in vitro screening of drugs for common and debilitating diseases such as age-related macular degeneration (AMD). Recently, retinal tissue has been generated from embryonic stem (ES) cells and induced pluripotent stem (iPS) cells derived from patients with inherited eye disorders, suggesting new opportunities for developing treatments for specific diseases. However, methods for eye cell production are currently inefficient and need to be improved before these approaches can be clinically translated.
The team has found that a particular secreted protein can effectively induce the formation of whole ectopic eyes in frog embryos and tissues through a combination of activation of the IGF signalling pathway and regulation of a number of developmental positional signals. The role and function of this protein and IGF in in vitro eye construction had not previously been studied. The team's data suggest that use of the protein and IGF will significantly improve current protocols of the in vitro generation of ocular tissue from human ES and iPS cells.
This project is investigating the mechanism of the protein-mediated eye induction in detail using Xenopus embryos and human stem cells. They are developing improved protocols for the induction of retinal tissue and whole eyes from human stem cells. They expect that the improved protocols will contribute to future eye research, such as eye-cup construction from iPS cells derived from patients with retinal degeneration.