Grant: Collaborative Health Research Projects (NSERC partnered)

"Dry eye disease is a major health-care issue and drain on health-care resources worldwide, with symptoms of discomfort, damage to the ocular surface, and a significant reduction in quality of life, with no current therapeutically effective treatments. Cells at the ocular surface, which forms a biointerface when sliding against an opposing tissue or contact lens, are subject to significant friction forces generated with eyelid blinking. These forces can be exacerbated by contact lens wear particularly in the presence of a compromised tear film, another symptom of dry eye. Proteoglycan 4 (PRG4), also known as lubricin, is a protein originally discovered in synovial fluid and on the surface of articular cartilage that has recently been discovered at the ocular surface. PRG4 has been shown to function in a dose-dependent manner, both alone and in combination with hyaluronic acid (HA; also present in synovial fluid and tears), to reduce friction at a cartilage-cartilage, and recently, an ocular surface biointerface, in a boundary mode of lubrication (surface-to-surface contact). Given the presence of PRG4 at the ocular surface where it presumably acts as a boundary lubricant, it is hypothesized that delivery of this protein, either alone or in combination with HA, will lead to decreased symptoms of dry eye, particularly in contact lens wearers. The planned experiments will be completed using novel and sophisticated biophysical, biochemical and biomechanical methods to first generate, purify, and characterize native and recombinant PRG4. Then assess their ability to both function as an effective friction-lowering boundary lubricant at contact lens - cornea/eyelid biointerfaces, and, with and without additional chemical modifications, interact with and improve properties of novel silicone hydrogel contact lens materials +/- HA incorporation. This work will result in the development of more comfortable contact lens materials and bandage contact lenses, and could lead to the development of the first real treatment for dry eye. The potential social and economic impact of this work to Canada is extensive. A novel, more lubricious contact lens and/or artificial tear solution would significantly improve the quality of life of millions of Canadians suffering from dry eye. "