Targeting a new regulatory mechanism to rescue phagocytosis

Research area: Macular degeneration
 
Aims and objectives

The retinal pigment epithelium (RPE) supports the functions and survival of photoreceptors, the cells that sense light and mediate vision.  Functionally deficient retinal pigment epithelium is a major clinical problems as these cells have functions essential for vision and are affected by inherited diseases, such as retinitis pigmentosa, as well as age-related conditions.

Photoreceptors develop a specialized domain that harvests light, which they constantly renew. This renewal process involves the shedding of old material, which is then internalized by the retinal pigment epithelium to clear the retina. This internalization process is called phagocytosis. If the retinal pigment epithelium is defective, photoreceptor debris accumulates and the retina degenerates. In cells from patients suffering from some forms of inherited blindness, phagocytosis is deficient. Age-related loss of vision can also be aggravated by impaired phagocytosis due to poorly functioning RPE. 

Work being carried out

Phagocytosis requires a molecular motor that drives the internalization of debris. Professor Matter and his team have discovered the mechanism that turns on this motor. In this pilot study, the team will focus on the development of therapeutic approaches by targeting this newly discovered regulatory mechanism to rescue phagocytosis in disease.

Outcomes and impact

The identification of targets and therapeutic strategies to rescue phagocytosis will have impact on academic and clinical beneficiaries in the short term: the supported research associate will be trained in stem cell approaches to model retinal disease and methods to target signalling proteins; collaborators focusing on translational research in developing drug and gene therapy-based approaches; and clinical colleagues who design and perform clinical trials. 

The long term beneficiaries will be patients as they will profit from more effective treatments. As a consequence, this will positively influence the NHS and the society as a whole. To reach these aims the team have started to establish a growing collaborative network that includes scientists working on gene therapy, induced pluripotent stem cells, structural biology and drug-design. 

 

Research details

Full Title

Targeting a new regulatory mechanism to rescue phagocytosis

Grant holder

Professor Karl Matter

Research Area(s)

Macular degeneration (Genetics / Inherited eye disease)

Start date

September, 2017

Award level

£40,569

Funding scheme

Project grant

Date: 13 August 2018

Grant reference: R180001A