Cynthia Yu-Wai-Man, MBBS FRCOphth
(Conferences / Seminars / Lectures)
NIHR Crick Clinical Research Fellow more information...
UCL Institute of Ophthalmology, London
Targeting the MRTF/SRF gene transcription pathway in Ocular fibrosis
Scarring and fibrosis are responsible for the pathogenesis or failure of treatment of most blinding diseases, with postoperative wound healing responses posing a major problem for most ocular surgery on a worldwide scale. Fibrosis is a complex multifactorial process but many therapeutic molecules only block a single pathway, for example inflammation or angiogenesis. The myocardin-related transcription factor/serum response factor (MRTF/SRF) pathway is involved in multiple pathways in the complex fibrosis process and thus represents a promising therapeutic target to prevent ocular fibrosis.
Our results show that inhibiting the MRTF/SRF pathway significantly decreases collagen matrix contraction, fibroblast dynamic index, and matrix remodelling in human conjunctival fibroblasts. We have also developed receptor-targeted liposome-peptide-siRNA nanoparticles as an efficient delivery system for MRTF silencing in conjunctival fibrosis. Furthermore, local delivery of novel inhibitors of MRTF/SRF-regulated gene transcription prevents scar tissue formation and significantly prolongs the long-term success of surgery in a validated rabbit model of glaucoma filtration surgery. As drug delivery represents one of the major hurdles in translational anti-fibrosis research, we are currently developing different drug delivery techniques for sustained release formulations in the eye. In addition, we are also studying potential novel genetic biomarkers to develop a more personalized and stratified approach in anti-fibrotic ocular therapeutics.