A rationale for gene targeting in glaucoma therapy.
One of the mainstays of glaucoma treatment is the use of drugs that decrease the secretion of aqueous humor fluid from the ciliary epithelium. Unfortunately, many currently available drugs that decrease aqueous humor production such as beta-adrenergic antagonists, may cause serious systemic side effects such as cardiac arrhythmias and arrest, pulmonary dysfunction, and CNS side effects such as decreased libido and depression. Efforts to develop effective aqueous suppressants that offer decreased morbidity and mortality in comparison to those currently available will likely rely on the ability to alter the function of specific cellular events which underlie aqueous humor production by the ciliary epithelium. However, the secretory process which results in aqueous humor production is incompletely understood and the identification of precise cellular mechanisms which underlie this process remain to be established. We will present a rationale for genetic approaches to regulate gene expression so that aqueous humor production may be specifically targeted in glaucoma patients. Techniques of gene transfer including homologous exchange recombination, and expression of antisense genes, will be discussed.
Wax
M
M
Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri.
Patil
R
R
D000818:Animals; D016375:Antisense Elements (Genetics); D001082:Aqueous Humor / Q000378:metabolism; D003001:Cloning, Molecular; D019204:GTP-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005901:Glaucoma / Q000628:therapy*; D006801:Humans; D016133:Polymerase Chain Reaction; D014162:Transfection / Q000379:methods
D016375:Antisense Elements (Genetics); D019204:GTP-Binding Proteins