Mayo Clinic pioneers gene therapy delivery system for glaucoma

September 01, 2004

ROCHESTER, Minn. -- Mayo Clinic researchers have demonstrated they can permanently transfer a functioning gene to targeted tissues within the eye. This success in animals is a first step in using gene therapy to treat glaucoma, a major cause of blindness worldwide. The research findings appear in the online issue of the leading vision science journal Investigative Ophthalmology and Visual Science (

Glaucoma causes pressure build up within the eyeball due to malfunctioning fluid drainage in the front of the eye. Blindness occurs when pressure progressively damages the optic nerve at the back of the eye. Eye specialists have long hoped for a permanent way to fix the malfunctioning outflow -- and they may now be a step closer because of the Mayo Clinic research.

Jellyfish and Green-eyed Cats

The gene that researchers transferred was a phosphorescent green protein naturally found in jellyfish. A routine procedure for ophthalmologists -- a single, tiny injection through the surface of the eye (cornea) -- was sufficient to introduce the jellyfish gene. The protein was encased in a specialized viral delivery system called a vector. When the vector reached the intended destination in eyes of laboratory cats, the vector's cargo gene produced the phosphorescent jellyfish protein in the cats' eyes. Researchers knew they were successful because the cats' eyes turned green when viewed with ultraviolet light at the targeted area. They also knew the effect was permanent because the cats' eyes continue to glow green more than a year after the procedure. The green-eyed cats have normal vision and are none the worse for the gene transfer.

"The main message here is that a specific kind of gene vector -- a lentiviral vector -- could be engineered to work really well as a delivery system to the particular tissue involved in glaucoma," says Eric Poeschla, M.D., a virologist in Mayo Clinic's Molecular Medicine program and the lead investigator on the project. "The next challenge is to replace the jellyfish protein with one that can safely treat glaucoma, which is what we are trying to accomplish now."

Significance of the Mayo Clinic Research Finding

This work has at least three important implications for gene therapy for glaucoma:
1. Glaucoma is a chronic disease that now is treated with surgery and then daily eyedrops for the rest of the patient's life. This treatment does not prevent blindness in many cases. Glaucoma affects 70 million people worldwide, many over age 65. Any new therapies would be welcome advances if they were permanent and eliminated the daily eye drops. This study's one-year success record offers hope of a permanent transfer in humans.

2. The Mayo Clinic researchers are the first to show that a lentiviral vector can effectively deliver genetic cargo to this glaucoma-related target in the eye.

Says Dr. Poeschla, "The results meet three criteria that have represented a main hurdle: enough delivery to enough cells; targeted delivery to the relevant cells; and permanence.'' He emphasizes that the Mayo Clinic research is still in its early stages and that no human participants have been involved.

3. The approach may be well suited to carry a gene that can prevent blindness by fixing the defect in the eye's fluid outflow system. Several such potential therapeutic transferable genes are the subject of current research at Mayo but are not ready for human testing. Using the jellyfish gene was a first step.

"Using eyedrops every day, lifelong, is very difficult for anyone, and there are many for whom the drops don't work, so the field as a whole recognizes that better treatments are needed to prevent blindness. That's why there's been a lot of interest in the concept of gene therapy as a way of permanently correcting the problem of this chronic disease,'' says Dr. Poeschla.
The Research Team:
In addition to Dr. Poeschla, other members of the multidisciplinary Mayo Clinic research team are: Nils Loewen, M.D. and Wu-Lin Teo of the Molecular Medicine Program, and from the Department of Ophthalmology, Michael Fautsch, Ph.D.; Cindy Bahler; and Douglas Johnson, M.D.

Their work has been supported by Fight for Sight, the National Institute of Allergy and Infectious Diseases and the National Eye Institute. [Long-Term, Targeted Genetic Modification of the Aqueous Humor Outflow Tract Coupled with Noninvasive Imaging of Gene Expression In Vivo, 2004 45: 3091-3098.]

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