Gene Therapy Approaches and Protocols to Deliver Genes for IOP-Reduction in Animals

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The glaucomas represent a heterogeneous group of optic neuropathies that result in progressive optic degeneration characterized by functional and structural impairment of ocular tissues. The two primary damaged ocular tissues in glaucoma are the trabecular meshwork in the front of the eye and the retinal ganglion cells in the back of the eye whose axons form the optic nerve. Elevated intraocular pressure (IOP) is the key risk factor for glaucoma, and drugs lowering IOP are the first line of defense in glaucoma therapy. Although self-administered topical ocular hypotensive eyedrops have been used for glaucoma management, patients encounter several problems, including non-compliance and incorrect drop instillation, especially patients suffering from motor function or coordination dysfunction. Unfortunately, as the majority of patients are asymptomatic, they become indifferent to the urgency of treatment. Even more problematic is that many patients require using multiple types of eye drops, and the likelihood of adherence decreases significantly, leading to worsening of the disease. Therefore, there is an urgent need for long-lasting IOP lowering therapy for glaucoma, and gene therapy offers such a possibility. Here, we describe several gene therapy approaches that are in development and protocols to deliver genes for IOP reduction in glaucomatous eyes.