Abstract: The tear film covers the anterior eye and the precise balance of its various constituting components is critical for maintaining ocular health. The composition of the tear film amphiphilic lipid sublayer, in particular, has largely remained a matter of contention. The limiting concentrations of lipid amphiphiles in tears have also posed considerable challenges to their detection and accurate quantitation. Using systematic and sensitive lipidomic approaches, we reported the most comprehensive human tear lipidome to date; and conferred novel insights to the compositional details of the existent tear film model, in particular the disputable amphiphilic lipid sublayer constituents, by demonstrating the presence of cholesteryl sulfate, O-acyl-ω-hydroxy fatty acids, and various sphingolipids and phospholipids in tears. Lipidomic analysis of human tear fluid from patients with various subtypes of dry eye syndrome (DES) revealed structure-specific lipid alterations in DES, which could potentially serve as unifying indicators of disease symptoms and signs.
The meibomian glands constitute the predominant source of lipid supply to the human tear fluid. Meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye and ocular discomfort, characterized by an unstable tear film principally attributed to afflicted delivery of lipids to the ocular surface. We investigated the longitudinal tear lipid alterations associated with disease alleviation and symptom improvement in a cohort of MGD patients undergoing eyelid-warming treatment for 12 weeks. Our preliminary data indicated that excess ocular surface phospholipase activity detrimental to tear film stability could be alleviated by eyelid warming alone without application of steroids and identify tear OAHFAs as suitable markers to monitor treatment response in MGD.
Abstract: Encapsulated-cell therapy (ECT) is an attractive approach for continuously delivering freshly synthesized therapeutics to treat sight-threatening posterior eye diseases, circumventing repeated invasive intravitreal injections and improving local drug availability clinically. Composite collagen-alginate (CAC) scaffold in ECT contains an interpenetrating network that integrates the physical and biological merits of its constituents, including biocompatibility, mild gelling properties and availability. An injectable CAC system that supported the growth of HEK293 cells with sustainable glial-derived neurotrophic factor (GDNF) delivery has been developed. Continuous GDNF delivery was detected in culture and in healthy rat eyes for at least 14 days. The gels were well tolerated with no host tissue attachment and contained living cell colonies. Most importantly, gel implantation in dystrophic Royal College of Surgeons rat eyes for 28 days retained photoreceptors while those gels containing higher initial cell number yielded better photoreceptor rescue effect. This rescue effect is clinically relevant as photoreceptor death is a common pathology in many retinal diseases. Moreover, since cells including autologous cells can be genetically engineered to secrete various therapeutic agents, CAC gel offers a flexible system design and is a potential treatment option for other chronic neurodegenerative diseases.
