Edition: U.S. / Global

Scientists Link a Defective Gene To a Leading Cause of Blindness

Published: January 25, 1990

A team of scientists in Boston has discovered a defective gene that results in one form of retinitis pigmentosa, an inherited disorder that is a leading cause of blindness.

The discovery, being reported today in the British scientific journal Nature, does not offer a treatment for the incurable disorder. But it does offer the prospect of a test that would help ophthalmologists determine who was affected.

A research test that the Boston scientists developed to find the defective gene is now under study as a possible practical diagnostic test, said Dr. Eliot L. Berson, who heads the team that made the discovery at the Massachusetts Eye and Ear Infirmary.

The discovery also creates new avenues of research for treatments for the disorder, said Meredithe L. Applebury of the Eye Research Laboratories at the University of Chicago. In a commentary in Nature, Dr. Applebury called the discovery a breakthrough in understanding the disorder because it is the first defective gene reported for any form of retinitis pigmentosa.

All forms of retinitis pigmentosa affect 100,000 people in the United States. The disorder takes its name from degeneration of the retina resulting from the deposition of pigments there. The retina, the layer of cells in the back of the eye, functions like film in a camera, relaying the images to the brain.

Progression of Disorder

Beginning in childhood, individuals with retinitis pigmentosa typically have night blindness. As adolescents, those with the disorder tend to lose peripheral vision. Then as they get older, they develop tunnel vision and many eventually become blind.

Retinitis pigmentosa can be inherited through one of several patterns. In the pattern involved in the new study, each child born to an affected parent has an equal chance of being affected. Dr. Berson estimated that up to 5,000 people in this country have the defective gene.

A team led by Dr. Thaddeus P. Dryja, an ophthalmologist and geneticist, is focusing on the form of the disorder resulting from the defective gene in hopes of making similar findings in the other types of retinitis pigmentosa. The finding is also being used to help gain a better understanding of how the defective gene produces the degenerative changes.

The defective gene is on chromosome 3. The defect involves a switch of two amino acids at a specific point in the gene.

Impact of Defective Gene

The defective gene affects a pigment called rhodopsin in the retina. Rhodopsin, also known as visual purple, is the light-sensitive chemical in the rod cells in the retina. The rod cells, which play an important role in night vision, are damaged early in the course of the disease.

The switch of one amino acid for another - histidine for proline - somehow sets off a cascade of reactions that over time lead to a collection of pigment within the retina. The deposit of the pigment is a scarring of sorts, resulting from the loss of rod cells. Side vision is lost as the scarring occurs in the periphery of the retina.

The researchers said they needed to improve their understanding of the biology of the cells in the retina before they could develop a treatment for retinitis pigmentosa.

The researchers found the defect in the rhodopsin genes in 17 of 148 cases studied. The scientists were aided by finding the defective gene in the affected members of a large family with the disorder. The researchers did not find it in 102 unaffected people who were not relatives of of those with the ailment.

The researchers said the fact that other families with retinitis pigmentosa do not have the defect in the gene was guiding further studies to find the defective genes responsible for other forms of retinitis pigmentosa.