Generating improved cells for the treatment of limbal stem cell deficiency

Research details

  • Type of funding: Project Grant
  • Grant Holder: Professor Lyle Armstrong
  • Institute: University of Newcastle
  • Region: North East
  • Start date: October 2022
  • End Date: September 2025
  • Priority: Treatment
  • Eye Category: Other
Brief Lay background

Chemical, thermal, or mechanical damage to the transparent surface of the eye (the cornea) can lead to the growth of the conjunctiva and its associated blood vessels over the cornea, also known as conjunctivalisation. The resulting cloudiness and associated irritation seriously affect patient’s quality of life leading to chronic and persistent eye pain and blindness. Limbal Stem Cells (LSCs), located between the clear cornea and the white part of the eye (known as the sclera), are key players in maintaining the outermost layer of the cornea.

The importance of limbal stem cells (LSCs) and the manifestations of their dysfunction, as a major cause of corneal blindness, is well documented and referred to as limbal stem cell deficiency (LSCD).

The main management option for the treatment of severe LSCD is surgical transplant of LSCs that have been cultured outside the body from biopsies taken from of the patient’s other eye. Transplant of LSCs from the eyes of other individuals (allograft) is well-known to have a poor outcome due to immune rejection and is therefore not a treatment option.

What problem/knowledge gap does it help address

Corneal blindness is the third leading cause of blindness worldwide after cataract and glaucoma, with 10 million people having bilateral corneal blindness. One major cause of LSCD is chemical or thermal burns. Traditionally, the cornea has been considered as an immune privileged site in the body. However, immune rejection remains the leading cause of corneal allograft failure, accompanied by vascularisation, inflammation, and corneal graft failure. It is difficult to find donors and not advised to maintain long-term immunosuppression of the cornea.  

Aim of the project

To create a bank of “off the shelf” LSCs that could be transplanted into any individual without the possibility of immune rejection.

Key procedures/objectives
  1. Generate hypoimmunogenic LSCs, that become invisible to the immune cells of a recipient, while still averting immune cell attack.
  2. Ensure that LSCs can become mature cells to form the outermost layer of the cornea (corneal epithelium).
  3. Assess immune cell responses in vitro and in vivo.
Potential impact on people with sight loss

Generating hypoimmunogenic LSC will greatly advance the treatment of total /severe LSCD. The novelty and innovation of this proposal is the development of an ‘off-the-shelf’ therapy that (a) will simplify the logistics and reduce the cost of delivering treatment to individual patients; (b) will provide readymade LSC source for use in emergency situations; (c) may reduce the requirement for systemic immunosuppression after transplant and (d) has not been attempted by other researchers in this field. Successful application of our proposed technology could also boost the regenerative medicine capacity of the UK by offering a unique treatment for a devastating blinding disease.