Project Summary
Glaucoma is generally recognized as a group of diseases that increase pressure in the eye through a malfunctioning of the trabecular meshwork (TM), which is an outflow track that maintains regular pressure in a healthy eye. Dr. Du and colleagues are developing and characterizing a mouse glaucoma model by inducing endoplastic reticulum stress in the trabecular meshwork. The team has identified a cell population from the TM and will apply these cells to the mouse model to investigate cell-based therapies for glaucoma and prevention of glaucomatous blindness.
Details. It has been suggested that age- and disease-related decreases of TM cellularity and accelerated apoptosis and senescence of the cells are associated with glaucoma. Increased endoplastic reticulum stress in the TM has been reported to cause intraocular pressure elevation. Dr. Du and colleagues are testing the different effects of several endoplastic reticulum stress inducers on cultured TM cells and extracellular matrix the cells secrete. The team will treat mice with the endoplastic reticulum stress inducers and characterize their effects on the corneal endothelium, TM, outflow facility, intraocular pressure and optic nerve damage by elevated pressure. They will optimize the delivery system and dosage. When the mouse model has been developed and characterized, the team will apply TM cells to the mouse model and investigate their ability of to remodel the structure of the outflow tract, decrease intraocular pressure and prevent optic nerve damage.
When this study is complete, Dr. Du and colleagues will have developed a mouse model that will elucidate the relationship between TM cellularity and intraocular pressure elevation. Their study will direct the development of cell-based therapies for glaucoma, which will lead to a revolutionary advance in treatment for glaucoma.
