Unraveling corneal fibrosis mechanisms via the study of vimentin expression in corneal cells on electrospun membranes

It is estimated that 135 million people have severely impaired vision because of a loss of corneal transparency. Corneal blindness is considered the 4th largest cause of blindness worldwide, after cataracts, glaucoma and macular degeneration. Corneal blindness is more prevalent in global south countries and is responsible for more than 5% of the currently total blind population, a high percentage of which are young children. There are multiple diseases directly associated with corneal blindness (Aniridia, keratoconus, Steven Johnson’s syndrome), however, the most common causes of corneal disease are due to external agents. Infections, trauma and ulcerations are three important factors that can damage the outer eye limiting quality of life significantly.
The frontline treatment for corneal disease often involves corneal transplantation and the use of autologous limbal cells cultured on a carrier (amniotic membrane, AM). The AM is a well-established cell delivery membrane which is flexible, it degrades within 3-4 weeks and, importantly, it has anti-inflammatory and anti-scarring effects. Unfortunately, the use of AM has drawbacks, specifically, the need for it to be accessed only using rigorous tissue bank protocols. Researchers at Sheffield have worked for years in the development of a synthetic membrane in order to offer a safer and cost-effective alternative to AM. This membrane has been manufactured using electrospinning, a versatile fabrication technique that allows the creation of fibrous and porous matrixes that resemble to a high degree the native extracellular matrix. The use of this electrospun membrane has proven to be successful in delivering cells onto a wounded corneal model, however, little is understood regarding its possible anti-scarring effects.
Fibrosis or corneal scarring can occur after injury and, depending of the seriousness of the injury, it can lead to corneal opacification and severe loss of vision. It is known that corneal fibrosis is characterised by the presence of myofibroblasts and irregular production of extracellular matrix (ECM) components; it is also known that during fibrosis there is a high level of expression of the intermediate filament protein vimentin (a protein required for cell migration and wound healing). In this project we aim to study the mechanisms that dictate vimentin expression via corneal cells seeded on electrospun cell delivery membranes. For achieving this we aim to combine the expertise of 2 leading junior scientists to develop a new approach to study corneal healing. The student undertaking this project will work with Dr. I. Ortega (expert in the development of biomaterials for corneal regeneration) and with Dr. A. KB Gad (expert in molecular biology with great expertise in the study of vimentin-mediated mechanisms). The student will work in a very supportive and multidisciplinary environment and she/he will be expected to develop activities at both biomaterials and molecular biology levels.