Rational Design of New In-Vitro Models of the Eye Through Biopolymer Self-Assembly

Retinal diseases, including age-related macular degeneration and diabetic retinopathy, are the leading cause of vision loss worldwide, and require innovative therapies to address them. The development of such therapies, including promising nanomedicines, relies on effective in-vitro models of the vitreous humour (VH) to understand delivery efficacy, pharmacokinetics and nanotoxicology, and be able to effectively screen potential therapies and accelerate the translation of new treatments to clinical application. Currently, there are no viable synthetic models which can mimic the mesostructure and physicochemical properties of the human VH, leaving ethically ambiguous and less representative animal models as the current standard.

Recent results have demonstrated that thermal processing of agarose solutions into gels offers a tuneable route to design the micron scale structure VH mimics, with implications for controlling transport properties. However, mechanistically, the role of concentration and temperature (rate) on biopolymer assembly is still not well understood. We seek, with this proposal, to view this through a lens of polymer phase behaviour and temperature-jump SANS to understand the nanoscale assembly of agarose when quenched into unstable "gel" regions of its solution phase diagram. We propose here a series of static, equilibrium and dynamic temperature jump experiments to study this assembly under precise control of temperature and cooling rate.