Ophthalmic molecular imaging and the role of the proteasome in retinal diseases

In the post-genomic era, characterisation of pathways involved in protein turnover has been a major area of research in medicine. The discovery of ubiquitin and thereafter the proteasome has revolutionised the understanding of the mechanisms responsible for protein regulation, also known as proteostasis. The proteasome acts as a nanomachine in eukaryotic and archaeal cells, responsible for proteolysis of soluble proteins that are tagged for degradation. This is achieved by selective ubiquitination of target proteins, a process that involves the covalent attachment of a poly-ubiquitin chain to the protein that is marked for recycling. In recent years, dysfunction of the ubiquitin-proteasome system has been linked to numerous human diseases which has led to the development of novel therapies using proteasome inhibitors. In this dissertation, we explore the contributions of the proteasome to retinal pathology and discuss strategies of therapeutic proteasome modulation in the retinal pigment epithelium.