A RATIONALE FOR GENE TARGETING IN GLAUCOMA THERAPY

One of the mainstays of glaucoma treatment is the use of drugs that de crease the secretion of aqueous humor fluid from the ciliary epitheliu m. Unfortunately, many currently available drugs that decrease aqueous humor production such as beta-adrenergic antagonists, may cause serio us systemic side effects such as cardiac arrythmias and arrest, pulmon ary dysfunction, and CNS side effects such as decreased libido and dep ression. Efforts to develop effective aqueous suppressants that offer decreased morbidity and mortality in comparison to those currently ava ilable will likely rely on the ability to alter the function of specif ic cellular events which underlie aqueous humor production by the cili ary epithelium. However, the secretory process which results in aqueou s humor production is incompletely understood and the identification o f precise cellular mechanisms which underlie this process remain to be established. We will present a rationale for genetic approaches to re gulate gene expression so that aqueous humor production may be specifi cally targeted in glaucoma patients. Techniques of gene transfer inclu ding homologous exchange recombination, and expression of antisense ge nes, will be discussed.