Formulation of a Lubricating, Self-Healing Gellan Gum Eyedrop to Prevent Corneal Scarring in Epidermolysis Bullosa Patients

Epidermolysis bullosa (EB) is a rare genetic disorder caused by mutations in genes encoding for components of skin extracellular matrix (ECM) with the most severe symptoms arising from collagen-VII mutations. Consequently, the ECM integrity is compromised and patients experience skin fragility and blistering in response to minor trauma or friction. The severity of EB varies widely between patients but at its most severe, the blistering occurs over the whole body and results in internal, potentially fatal fibrosis. Treatments for EB primarily focus on managing symptoms/preventing infections. Patient quality of life is, however, still severely compromised and current treatments often fail to provide sufficient relief.<br/>Safeguarding ocular function in EB patients is particularly challenging. EB-associated mutations can manifest in the eyelid and cornea. Even the act of blinking can then trigger extensive corneal scarring, resulting in severe eye pain and impaired vision.<br/>This project is developing a lubricating, self-healing gellan-gum fluid gel eye drop that patients can purchase at low cost and apply daily to prevent ocular friction and scarring. Fluid gels were formulated at a variety of shear rates to evaluate the impact of formulation parameters on fluid gel rheology and lubrication. All samples exhibited a friction coefficient comparable to current eye drops. Moreover, the applied shear rate was found to directly influence fluid gel stiffness and stress responses without impacting viscosity. The changes in rheology also translated into alterations in the lubricating properties of the fluid gel, with increases in gel stiffness correlating with decreases in friction coefficients. Furthermore, we have successfully decoupled high viscosity from functionality by controlling the structuring of the material. This allows us to generate optimal rheological properties for eye drop retention without impairing the ability to extrude the solution through an eye dropper<br/>Additionally, our formulation has been shown to protect cultured fibroblasts from undergoing differentiation into myofibroblasts in response to shear—a key mechanism of fibrosis. The fluid gel eye drop also sequesters pro-fibrotic factors like TGF-beta and inhibits downstream expression of pro-fibrotic genes. This highlights the significant potential of our formulation to not only provide lubrication but also actively prevent fibrosis, a major concern in ocular health.