Challenges in neuroprotective nanomedicine development: progress towards noninvasive gene therapy of glaucoma

Over the past decade the application of gene therapy of retinal diseases such as glaucoma has produced promising results. However, optic nerve regeneration and restoration of vision in patients with glaucoma is still far from reality. Neuroprotective approaches in the form of gene therapy may provide significant advantages, but are still limited by many factors both at the organ and cellular levels. In general, gene delivery systems for eye diseases range from simple eye drops and ointments to more advanced bio- and nanotechnology-based systems such as muco-adhesive systems, polymers, liposomes and ocular inserts. Most of these technologies were developed for front-of-the-eye ophthalmic therapies and are not applicable as back-of-the-eye delivery systems. Currently, only the invasive intravitreal injections are capable of successfully delivering genes to the retina. Here we review the challenges and possible strategies for the noninvasive gene therapy of glaucoma including the barriers in the eye and in neural cells, and present a cross-sectional view of gene delivery as it pertains to the prevention and treatment of glaucoma.