Background: Age-related macular degeneration (AMD) is the leading cause of impaired vision, and often blindness in adults. Although a multitude of genetical and environmental factors contribute to its development, ageing represents the highest risk factor. At present, treatments for AMD are limited – they only target a small subset of sufferers and even then, do not provide long-term benefits. Central to AMD onset and progression are the malfunction and degeneration of the retinal pigment epithelium (RPE) – the retinal outermost cellular monolayer essential for photoreceptor function. RPE functions become disrupted with age and are associated with pathological events, both within RPE cells and in the underlying structures.
Work on which the PhD project builds: The causative processes leading to AMD are poorly understood at the molecular level, although impaired proteolytic balance has been implicated. RPE modulation of intra-and extracellular proteolysis is crucial for maintaining the structural/functional integrity of the retina/choroid.
Understanding the mechanisms through which ageing and oxidative stress lead to changes in normal RPE physiology is essential for developing preventative and therapeutic approaches for ensuring the ageing population can retain effective eyesight. The project will make use of recent gene expression profiling of RPE cells at different ages and in response to specific age-related stresses known to induce oxidative stress.
The aim of the PhD project is to characterise RPE functional pathways affected by age-related response to oxidative stress. The project will ensure development of highly topical skills and a thorough training in molecular and cell biology.
Experimental approach and training: The student will be based in the Molecular Biology and Mechanisms of Disease Group in Liverpool (http://www.liv.ac.uk/paraoan ) and will benefit from the very successful national and international collaborations of the group. The experimental approach will make use of in vitro human cell-based models, including recently developed “disease/AMD-in-a-dish” models, ensuring training in functional molecular/cellular assays and imaging of proteins of interest. Enhanced expression (with tagged fluorescent fusion constructs) and knock-down endogenous expression will be used to investigate the function of different proteins of interest on the modulation of normal, ageing and disease-specific RPE cellular processes.
Informal enquiries are welcome and encouraged to be made to Professor Luminita Paraoan ([Email Address Removed]).