Age Related Eye Conditions
PROFESSOR LUMI PARAOAN
PROJECT TITLE: In vitro molecular modelling of age related macular degeneration
PROJECT TIMESCALE: 13 February 2017 – 12 February 2020
PRINCIPAL INVESTIGATOR: Professor Luminita Paraoan
PHD RESEARCH ASSISTANT: Dr Umar Sharif
The eye is the amazing organ that provides the sense of vision by converting light into electrical impulses that are passed onto the brain for analysis as visual images.Light enters the eye initially being refracted by the cornea and will eventually reach the back of the eye where the photosensitive retina lies. The central region of the retina is called the macula lutea, which is a specialised region of the retina responsible for high acuity and colour vision. With age, this region can undergo pathological changes causingimpairment and even loss of central vision and development of diseases such as age-related macular degeneration (AMD).
Age-related macular degeneration (AMD) is the leading cause of irreversible, severe loss of vision in the elderly population of the developed world. Approximately 50 million people suffer from AMD worldwide and this number is predicted to increase by 3 fold over the next 20 years, highlighting AMD as a major public health issue. Pathological changes that occurare primarily due to dysfunction and degeneration of a highly specialised monolayer of post-mitotic cells called retinal pigmented epithelial (RPE) cells, which are essential for maintaining the retina.Essential functions of the RPE rely on keeping the appropriate level of proteins both inside and outside the cells. We are particularly interested in identifying and characterising the mechanism of action of proteins with regulatory roles for maintaining this balance. Evidence suggests that dysregulation of this process contributes to RPE dysfunction with age and contributes to development of AMD. We aim to understand how this occurs, thus contributing to potential novel avenues to prevent, alleviate or treat this disease that has a major impact on the quality of life.
The project funded by The Humane Research Trust will enable us to specifically address the questions concerning the mechanism of action of key proteins present in the RPE by making use of innovative gene editing techniques. These allow us to develop novel in vitro experimental RPE models which mimick their behaviour in the context of the disease in a laboratory dish, hence the concept of “disease in a dish”. Such models are instrumental for the detailed study of protein trafficking inside the cell and the characterisation of abnormal events contributing to the degenerative processes occurring in the presence of protein variants that are associated with the disease. The results obtainedwill help assess if countering aberrant trafficking or intracellular processing of disease-associated proteins can prevent or delay the progress of AMD.
The generous support provided by The Humane Research Trust for our research is gratefully appreciated and acknowledged.
Figure legend: Image shows the gross anatomy of the human eye in a vertical sagittal section. The innermost layer (red) consists of the retina which is the light sensitive part of the eye. The zoomed in image is a diagrammatic representation of the different cell types found in the retina including the photoreceptor cells as well as retinal pigmented epithelial (RPE) cells.