Gene Therapy in Glaucoma
Glaucoma is uniquely well-suited to gene therapy. The trabecular meshwork or Schlemm's canal can be targeted by anterior chamber injection due to aqueous humor outflow, and RGCs can be targeted with intravitreal injection due to their proximal inner retinal location to the vitreous. Although these efforts are still in their relative infancy, successful gene therapy experiments have been directed toward modification of trabecular meshwork extracellular matrix and cytoskeleton components using adenovirus and lentivirus constructs, and modulation of apoptosis and intracellular signaling pathways in RGCs has been achieved with AAV constructs. However, idiosyncratic immune responses leading to human deaths have been reported using systemic administration of both adenoviral and AAV vectors. The decreased amount of viral vector used for ocular administration should reduce this risk considerably, but caution is certainly warranted with any human gene therapy that is undertaken. Nonviral techniques are also being employed for gene transfer, using cationic lipid delivery systems (lipofection) or the use of electric current (electroporation) to deliver DNA sequences into target cells. These nonviral techniques provide a complementary approach that could minimize the immune responses that can limit therapeutic viral vector gene transfer trials.
