Inflammation in the cells that form barriers to protect the eye

Research details

  • Type of funding: PhD Studentship
  • Grant Holder: Professor Karl Matter
  • Institute: UCL Institute of Ophthalmology
  • Region: London
  • Start date: October 2016
  • End Date: November 2019
  • Priority: Causes
  • Eye Category: Ocular inflammatory


Inflammation is a normal response that helps the body get rid of infection and protect against tissue damage. But long term (chronic), uncontrolled inflammation leads to serious disease including conditions that affect the clear front surface of the eye (the cornea) or the light-sensitive layer at the back of the eye (the retina). Chronic inflammatory conditions are often linked to ageing and are hard to treat well.

In this project the student and team are looking at the types of tissues known as epithelia – sheets of cells that form a protective barrier, such as the cornea and the retinal pigment epithelium, which separates the retina from the blood. Problems with these barriers are linked to inflammation and blinding conditions.

They are studying a protein that helps form channels between cells that mean the cells can stick to together to form sheets. It also helps control what can get into and out of the cells. The team’s previous work makes them think the protein can sense problems in barrier tissue and is involved in controlling inflammation. They’re aiming to find out if it would make a good new target for developing treatment
  • Scientific summary

    Ocular epithelial inflammation: Regulation by a transmembrane protein of tight junctions

    Functional epithelial tissue barriers are essential for the eye. Infectious, acute and chronic inflammatory diseases lead to epithelial barrier disturbance and, often, loss of barrier function. Epithelial tissue formation requires cells to interact via intercellular adhesive structures including tight junctions, which control paracellular permeability. Tight junctions are also signalling hubs that guide cell behaviour and function. Tissue damage due to infection and inflammation often affects the integrity of tight junctions; however, whether tight junctions participate in controlling the epithelial inflammatory response is not known. MarvelD3 is a transmembrane protein of tight junctions that we have shown to regulate the epithelial stress response, a mechanism that involves endocytic recycling and junctional recruitment of cytosolic signalling components.

    Here, the team asks if MarvelD3 is a sensor that transmits junctional damage to the cell interior to guide proinflammatory signalling and whether its associated signalling mechanisms are relevant for inflammatory disease in ocular epithelia. They are using loss and gain of function approaches to determine if and how MarvelD3 guides proinflammatory signalling, and whether its junctional localisation and endocytic recycling are part of a mechanism that senses tissue integrity. Patient tissue samples will be used to determine if results obtained with in vitro systems indeed reflect molecular changes observed in diseased tissue. The team expects that this PhD project will identify a new molecular mechanism that links tight junction and ocular tissue integrity to proinflammatory signalling and provide insight into the importance of such a regulatory mechanism for inflammatory diseases affecting ocular epithelia.