Reducing DEB/JEB eye scarring

EB can affect the cornea resulting in severe pain and impaired vision. This project is to grow cells from human corneas that can undergo scarring behaviour like those in the eyes of people with EB. These can then be used for the first tests of a potential anti-scarring eyedrop to save the sight of children with EB.

Prof Martin will grow human eye cells from donated corneas in his laboratory and use siRNA technology to reduce the amount of collagen (to mimic RDEB) or laminin (to mimic JEB) that they produce. The first stage of this project will be to confirm that this works and that the cells start to behave as if they are from an EB patient. Then, an anti-scarring substance can be tested on these cells to see if it reduces the EB changes and how it does this. If this provides evidence that the therapeutic substance is effective, it could be progressed to further trials.

Read more in our researcher's blog.

There is no substitute for loss of sight.

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About our funding:

Research leader	Prof Keith Martin
Institution	Centre for Eye Research Australia (CERA), University of Melbourne, Australia
Type of EB	RDEB and JEB
Patient involvement	None
Funding amount	£15,000
Project length	1 year
Start date	1 July 2024
DEBRA internal ID	GR000016

Latest progress summary:

Due 2024.

About our researchers:

Research leader: Keith Martin is Honorary Senior Research Fellow at the University of Cambridge and Head of Ophthalmology at University of Melbourne (UoM). Prof Martin has been Director of the Centre for Eye Research Australia (CERA) for three years, but his Cambridge laboratory remains active, supported in part by Fight for Sight. As Director of CERA, Prof Martin leads a diverse group of researchers conducting world leading basic and clinical studies in eye research. Prof Martin is a glaucoma specialist with a particular interest in developing new therapies to protect and restore vision in glaucoma.

Co-researchers: Dr Gink Yang has a strong scientific background in epidermolysis bullosa (EB) and EB-induced squamous cell carcinoma, regenerative medicine, wound repair and genetics. Dr Yang has published on EB-induced skin blistering, EB-kindler syndrome, and squamous cell carcinoma. He was awarded a CERA Innovation Fund grant to validate an anti-scarring factor for the cornea in 2021 and has obtained promising results for this research. He now hopes to validate the efficacy of this factor for corneal scarring in recessive and junctional EB. The project will be led by Dr Yang day to day, with progress tracked by Prof Martin on a monthly basis. Prof Daniell will provide additional clinical and scientific support.
Prof Mark Daniell is Head of Corneal Research at CERA / UoM and leads the Corneal Unit at Royal Victorian Eye and Ear Hospital. The research themes of Prof Daniell’s laboratory include corneal clinical science, surgical device development, corneal dystrophies, keratoconus, and corneal scarring – a new theme led by Dr Gink Yang, an Early Career (PhD awarded in Aug 2020) Research Fellow at CERA and Honorary Fellow at UoM.

Why this research is important:

An international patient survey on EB patients in 2020 reported patients commenting that corneal erosions ‘‘usually completely shut down my life’’ and ‘‘are one of the worst secondary issues associated with EB, if not the most painful.’’ The proposed project is of basic research nature; however, the overriding aim of the project is to develop a novel anti-scarring eyedrop formulation for EB patients experiencing corneal erosion and scarring. The proposed research may also reveal additional novel targets for EB-induced corneal scarring. This will ultimately accelerate the research and development of other drugs for EB patients in the future.

Prof Keith Martin

Read the 2020 international survey of EB patients here.

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Researcher’s Abstract:

Grant Title: Reducing corneal scarring in epidermolysis bullosa with a novel factor

Brief background and need for the research: Epidermolysis bullosa is a rare inherited disease that causes blistering of the skin and mucous surfaces of the body, including the eye. Living with this disease is like living with third degree burns. Sufferers have restricted mobility and often must be bandaged every day to protect and medicate their painful wounds. Specific mutations in certain types of this disease also have serious impact on the health of the cornea – the outer transparent layer of the eye. The cornea is an important part of our visual system, and any erosion or scarring to the cornea can result in severe eye pain and impaired vision. Current clinical treatments for epidermolysis bullosa including the use of contact lenses, lubrication, and antibiotics to reduce symptoms, but do not offer a solution to prevent scarring in the cornea. Corneal scarring can cause serious deterioration to vision, and hence quality of life, for those already fighting unimaginable daily battles.

Aim of the study: Our research aims to develop an anti-scarring eyedrop for epidermolysis bullosa sufferers using a novel factor.

Method of investigation: The novel factor has been shown to restrict molecular mechanisms responsible for corneal scarring and improve corneal transparency in our preliminary studies. The objective of the project is to validate its efficacy in epidermolysis bullosa models using human corneal cells. The human corneal cells will be isolated from donated corneas and transiently reprogrammed to mimic the characteristics from specific forms of epidermolysis bullosa. We will then administer this factor in cell culture following induction of fibrosis and assess its efficacy using biochemistry and microscopy.

Clinical benefit: Given the complex medical implications of epidermolysis bullosa, it is important to ensure that pharmaceuticals under development for this disease are target specific and will not induce unacceptable side effects. Our laboratory-based study using isolated human corneal cells and target-specific gene modifications to model disease subtypes will facilitate the validation of a potential new therapy. Results from this study will reveal if the anti-scarring factor is safe and effective at a cellular level. This is an important step towards preclinical trials, where the systemic effect of the anti-scarring factor can be further assessed. The overriding aim of this research is to develop an eyedrop using the anti-scarring factor for patients suffering from epidermolysis bullosa-induced corneal scarring. Once developed, the eyedrop will be administered to patients both as a prevention and treatment for corneal erosion/scarring. This could potentially reduce the need for prolonged use of antibiotics and steroids, thus reducing the potentially harmful side effects from these existing treatments.

Researcher’s progress update: