Glaucoma: genes, phenotypes, and new directions for therapy

Abstract

Glaucoma, a leading cause of blindness worldwide, is characterized by progressive optic nerve damage, usually associated with intraocular pressure. Although the clinical progression of the disease is well defined, the molecular events responsible for glaucoma are currently poorly understood and current therapeutic strategies are not curative. This review summarizes the human genetics and genomic approaches that have shed light on the complex inheritance of glaucoma genes and the potential for gene-based and cellular therapies that this research makes possible.

Figure 1. Schematic diagram of eye structures involved in aqueous humor dynamics.

Aqueous humor is produced by the ciliary body and passes from the posterior chamber through the pupil into the anterior chamber into the trabecular meshwork, Schlemm’s canal, and finally into the episcleral venous system. The alternative path is the “uveoscleral outflow” that drains fluid through the ciliary muscle into the supraciliary and suprachoroidal spaces and then out of the eye through the sclera. Approximately 80% of aqueous humor is removed by the conventional trabecular meshwork pathway, and the remainder is removed by the uveoscleral pathway. Elevated IOP in glaucoma is caused by alterations to the conventional trabecular meshwork pathway. The figure adapted from Berwick Eye and Surgicentre ( www.berwickeye.com.au/glaucoma.htm).

Figure 2. Schematic overview of experimental therapeutic approaches to glaucoma, including intraocular delivery of neuroprotective molecules, viral-mediated gene transfer, and stem cell therapies.