Researchers have identified a gene that, when mutated, appears to cause the juvenile form of glaucoma, an aggressive form of the disease that can strike teenagers. The finding, in tomorrow's issue of Science,* could lead to a quicker diagnosis for potential victims of juvenile and adult glaucoma, a disease that blinds almost 12,000 Americans each year.
A team led by Edwin Stone and Val Sheffield of the University of Iowa College of Medicine in Iowa City searched for the gene in more than 100 people with juvenile glaucoma in eight families. The team members narrowed their search to a region of about 1 million base pairs on chromosome 1. Combing the Human Genome Project's gene catalog, they found three suspect genes in this DNA stretch. Closer scrutiny revealed that one gene, encoding a protein called TIGR, was mutated in five of the eight families tested, but not in 100 healthy controls. The finding "is the first time anybody has ever identified something specific ... that indicates what might be going on," says Ellen Liberman, a glaucoma expert at the National Eye Institute. It may also lead to better tools for early diagnosis of the more common adult-onset form. Although juvenile glaucoma accounts for fewer than 1% of all cases, early indications are that mutations in the TIGR gene are behind at least 3% of adult-onset cases as well.
The gene in question is a likely culprit. TIGR is made by the eye's trabecular meshwork cells, which help regulate eye pressure by controlling the drainage of fluid from the eye as new fluid is produced. Glaucoma is characterized by rising fluid pressure in the eye that damages the optic nerve. Some experts suspect that an excess of TIGR could cause increased eye pressure by gumming up the space between the meshwork cells and blocking the normal outflow of fluid from the eye. Whether the mutations in the TIGR gene have a similar effect or lead to glaucoma in some other way remains to be established, however. Says Liberman: "We have a lot of work to do to figure out what this protein actually does."