Role of Ocular CYP2D6 in Glaucoma Drug Metabolism

An individual’s response to a particular drug can vary greatly. The variations in drug response between individuals affects both the drug’s effectiveness and its side effects. The fields of pharmacogenetics and pharmacogenomics attempt to determine whether such differences in drug response are attributable to a diversity in genes and their proteins. Dr. Moroi’s research is testing the hypothesis that certain variations in drug metabolizing genes contribute to the variation in eye-pressure response to glaucoma drugs. He hopes to describe the expression of the drug-metabolizing enzyme, cytochrome P450 2D6, in eye tissues and to determine the functional expression of this gene in the ocular tissues that express it. This is being done through the development of biochemical assays to detect the metabolism of beta-blockers, a major class of glaucoma drugs metabolized by this enzyme. If drug-metabolizing enzymes are found to be present in the eye, Dr. Moroi will examine them as genetic markers for eye-pressure response to certain glaucoma drugs. The long-term goal of this research is to identify the optimal therapy for individuals with glaucoma based on their genetic profile while minimizing progressive visual field loss.