Promoters for Glaucoma Gene Therapy

Curtis Brandt, PhD
Board of Regents of University of Wisconsin (Madison, WI)
Year Awarded:
2001
Grant Duration:
April 1, 2001 to March 31, 2003
Disease:
Glaucoma
Award Amount:
$70,000
Grant Reference ID:
G2001005
Award Type:
Standard
Award Region:
US Midwestern

Promoters for Glaucoma Gene Therapy

Details


Through mechanisms that are not understood, the increased IOP of glaucoma triggers specialized cells in the retina called retinal ganglion cells (RGC) to enter a process called programmed cell death, or apoptosis. The RGC are critical in relaying signals from the retina to the brain, and when these cells die, portions of the retina can no longer send visual signals to the brain. If IOP is increased long enough, most or all of the RGC die, resulting in blindness. The primary therapeutic approaches for glaucoma rely upon agents that can have unwanted side effects and surgery is sometimes needed. One potential remedy for these problems is the use of gene therapy. Any gene that increases the flow of fluid through the trabecular meshwork (TM), reduces the production of the fluid, or protects RGCs could be useful. But before gene therapy can be attempted, a carrier agent, or vector, is required to deliver and turn on the therapeutic gene. Dr. Brandt has recently shown that a modified Herpes simplex virus (HSV) vector can deliver a foreign gene to TM cells or the non-pigmented ciliary body epithelium (NPCE) cells that make the aqueous humor. The next step is to identify a suitable promoter (a gene element) that can induce the targeted cells (i.e., TM cells) to turn on a gene that the promoter has been linked to. Dr. Brandt is attempting to identify and isolate suitable promoters that could be used with HSV vectors in gene therapy. This project is a continuation of a BrightFocus-funded study of the same name, begun in 1999.

Publications

Filla, M.S., Liu, X., Nguyen, T.D., Polansky, J.R., Brandt, C.R., Kaufman, P.L., and Peters, D.M. (2002) TIGR/MYOC localizes to trabecular meshwork extracellular matrix in vitro and binds to fibronectin. Invest. Ophthalmol. Vis. Sci. 43:151-161.  

Borras, T., Brandt, C.R., Nickells, R., and Ritch, R. (2002) Gene therapy for glaucoma: treating a multifaceted, chronic disease. Investigative Ophthalmology Visual Science. 43(8):2513-2518.  

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