Reduced 3 Alpha HSD Activity in POAG

Primary Open Angle Glaucoma (POAG) is the most common form of glaucoma and is a leading cause of blindness in the United States. POAG is recognized to be an inherited disease, although the responsible gene has not yet been identified. Several lines of evidence obtained in the past few years suggest that the gene for the enzyme 3α-Hydroxysteroid Dehydrogenase (3α-HSD) may be altered in POAG. 3α-HSD is an enzyme which converts an ocularly hypertensive metabolite (5ß-DHF) to a hypotensive one (3α,5ß-THF) and may be involved in the regulation of intraocular pressure. In addition, clinical trials of 3α,5ß-THF, the compound produced by 3α-HSD, has demonstrated that this compound significantly lowers the intraocular pressure in POAG patients. In a small Pilot Study, the activity of the enzyme 3α-HSD was found to be reduced in peripheral blood lymphocytes from patients with POAG. Peripheral blood lymphocytes are easily obtainable from subjects.

Hypothesis

For many POAG patients the disease is related to a mutation in the gene for 3α-HSD which results in the synthesis of 3α-HSD protein with decreased enzymatic activity.

Specific Aims

This project proposes to extend the initial Pilot Study to a much larger group (200) so that the exact relationship between lymphocyte 3α-HSD deficiency and POAG can be determined.

Long-Term Goals

It may be possible to use a blood test to objectively identify patients with POAG or at risk of developing the disease. It is anticipated that by identifying POAG patients earlier in the course of the disease, intervention can be begun earlier with perhaps greater success. In addition, it may be possible to identify patients who will not develop POAG despite the presence of “traditional” risk factors such as family history of the disease, elevated IOP, age or race.