Novel approaches for the treatment of dry eye disease
Dr J Gabhann
Prof C Murphy
Monday, December 02, 2019
Competition Funded PhD Project (Students Worldwide)
Inflammation is a key unifying factor for a range of ocular surface inflammatory diseases including autoimmune mediated dry eye disease (DED) and complications with corneal transplantation (CT). While each condition has a specific presentation there are elements of overlapamong them, most strikingly (i) immune-mediated inflammation driving disease pathology (ii) use of immune suppression/corticosteroids as a primary treatment option (iii) lack of mechanisms to effectively deliver therapeutics to the ocular surface and (iv) no diagnostic tests that allow identification of patients who will go on to develop further complications. Current therapies for DED, including artificial tears and antiinflammatory agents, have been proved largely inadequate as they fail to address the underlying inflammatory component. Recently non-coding microRNA species have been shown to regulate inflammation. Synthetic DNA sequences that mimic or antagonise miR function are a new class of drugs which exhibit enhanced stability, target specificity and bioactivity.
An ability to effectively modulate miR function and thus ocular inflammation has wide ranging therapeutic and commercial implications. This proposal aims to address these needs by identifying bio-markers and targeting the molecular mechanisms that underpin DED disease pathology, with a strong emphasis on translational application of these findings to develop both diagnostics and novel therapeutics. Wehave generated promising preliminary data from epigenetic studies in Sjogrens Syndrome (SS) patients, who present with severe autoimmune mediated DED, where we have identified novel microRNAs (miRs) that contribute to ocular inflammation and the development of DED. We will build upon these findings and the strengths of our multidisciplinary team to progress personalised medicine in ocular surface diseases by developing and optimising an idealised medical device for effective and targeted delivery of anti-inflammatory agents to the ocular surface, which will lead to critical improvements in healthcare in areas of societal and economic burden, generating health and economic impact.