Development of conjunctiva and retinal models for better eye disease
study and treatment.
PhD Supervisor(s): Dr Ying Yang, Dan Nguyen and Alicia El Haj
Eye diseases such as macular degeneration and glaucoma are leading causes of irreversible blindness. If left untreated any vision lost cannot be regained. Increased intraocular pressure (IOP) due to elevation of aqueous humour pressure within the eye is the primary risk factor for the development of glaucoma, which is a disease with characteristic compositional and structural changes to the optic nerve head (ONH). Increased hydrostatic pressure and mechanical trauma has been shown to initiate and activate glial cells such as astrocytes and Muller cells.
It has been demonstrated that activated glial cells will express matrix metalloproteinases and/or reduce calcium and potassium channel flux. These changes can weaken the architecture of the ONH and facilitate collapse of lamina cribrosa beams, leading to injury and death of the retinal ganglion cells (RGC) that pass through these structures. In glaucoma with current medication and glaucoma filtration surgery (trabeculectomy) it is possible to lower the intraocular pressure and in most circumstances prevent further visual loss as a result of retinal ganglion cell death. Although glaucoma surgery can be successful in the majority of cases, over time over 25% of surgeries fail with subsequent elevation of IOP. Whilst retinal treatment is even less optimal. Surgical failure is related to conjunctival scar tissue formation. One of the mechanisms leading to tissue remodeling and scarring is shear stress as a result of aqueous fluid flow. Fluid shear stress has been reported to stimulate extracellular matrix synthesis in other tissue types.
Establishment of better retinal and conjunctival tissue models to investigate the regeneration of retinal cellular community and reduce the failure rate of trabeculectomy surgery are highly demanded.
