Gene therapy for glaucoma

Abstract

Glaucoma is a chronic progressive disease for which ideal treatment would provide a localized long-lasting therapy with minimal side-effects. A gene therapy approach in which a mutated gene is replaced or inactivated, or in which a new gene is introduced, could provide a novel and more effective way of targeting the disease. The aim of this review is to provide an update on recent advances in the field of gene therapy for the treatment of glaucoma. Both viral and nonviral vector gene delivery systems have been used to target specific tissues involved in the pathogenesis of glaucoma. These tissues include the trabecular meshwork, ciliary body, ciliary epithelium, Müller cells, and retinal ganglion cells. Recent studies in large animal models have demonstrated effective long-term gene expression in the trabecular meshwork following intracameral delivery of adeno-associated viral vectors and lentiviral vectors with limited effect on surrounding ocular tissues. Other promising studies have focused on vector-mediated expression of neurotrophic factors and have demonstrated a neuroprotective effect following intravitreal delivery of vectors in glaucomatous animal models. Given the recent laboratory studies utilizing gene therapy techniques to lower intraocular pressure and to provide neuroprotection, and the continued development of tissue-specific vectors, it seems that we are well poised for a new generation of treatments for glaucoma.