Gene therapy of glaucoma: Just an attractive experimental approach?

Abstract

AbstractIn recent years, much progress has been made in the identification of the genes involved in the physiology of glaucoma and the development of new gene‐based therapies. The eyeball has ideal characteristics for gene therapy due to its location and immunological properties. Gene delivery through viral and particle‐based vectors to target tissues makes gene therapy a more specific and effective treatment than existing conventional treatments. Experimental gene therapy strategies for glaucoma primarily targets trabecular meshwork (TM) (to decrease intraocular pressure) and retinal ganglion cells (for neuroprotection).A chronic disease such as glaucoma, requires the use of vectors that allow long‐term gene expression with low toxicity and immune response. Some examples of experimental gene therapy for glaucoma are the efficient transduction of self‐complementary adeno‐associated viruses – metalloproteinase 1 (MMP1) into the TM in a steroid‐induced ocular hypertension model in sheep1. On the other hand, different studies have reported an increased survival of retinal ganglion cells after a single intravitreal injection of adenoviruses carrying brain‐derived neurotrophic factor (BDNF) in a rat model of glaucoma2.To develop gene therapy at a therapeutic level it is necessary to broaden our knowledge of the expression and regulation mechanisms of candidate genes in order to control the efficiency and stability of their effect. The specificity of the vectors and the safety to prevent their spread to the rest of the organism must also be improved. Thus, it is necessary to continue devoting efforts to the development of safe and effective gene therapy for glaucoma.