Understanding the molecular mechanisms of drusen formation and therapeutic rescue in a model of macular dystrophy

Professor Jacqueline van der Spuy, University College London- £293,803

What is the problem?

Doyne honeycomb dystrophy (DHD) is an inherited condition diagnosed in early adulthood that leads to the progressive loss of vision. The condition is characterised by the accumulation of drusen (clumps of lipids and proteins) underneath a layer of cells called the retinal pigment epithelium (RPE). The RPE supports the overlying light-sensing cells in the eye. A major gap in knowledge is how the genetic change that causes DHD ultimately leads to the formation of drusen.

What are they doing?

Professor Jacqueline van der Spuy and her team have previously used stem cells from DHD patients to develop an ‘RPE-in-a-dish’ model in the laboratory. This disease model replicates the accumulation of the drusen under the RPE. Moreover, they have developed a therapy that reduces the formation of these drusen in this patient RPE model.

The current project will use the patient-derived disease model to assess genetic changes in the condition and compare these with the consequent functional changes in the cells associated with the drusen. Comparing these changes following therapeutic treatment of the disease model will allow the researchers to pinpoint the pathways leading to the drusen formation and determine how they are rescued by the therapy.

How can this help?

This study will further validate the therapy they have previously developed as an effective treatment for DHD in the cell model, critically highlighting which pathways are rescued and therefore implicated in the disease progression.