Biological cause of one form of blindness identified by SLU researchers

Saint Louis University researchers have discovered the cause of one form of retinitis pigmentosa, a type of genetically inherited blindness. The research, which will be published Tuesday in the April 27 Proceedings of the National Academy of Sciences (PNAS), opens the door to the development of new treatments.

The research was based on genetic information provided by several blind members of a South African family. The laboratory of William Sly, M.D., chair of the department of biochemistry at Saint Louis University School of Medicine, collaborated on the research with scientists from UCT/Groote Schuur Hospital in South Africa. Further evidence in support of their research was provided by Dr. Kang Zhang at the University of Utah.

The research began when a “gene hunt” involving five large families led the South African scientists to discover a genetic mutation not previously known to be involved in retinitis pigmentosa. The discovery was unusual because this gene was expressed only in the kidney and in micro-capillaries such as the capillaries beneath the eye, and not in the retina itself; typically, genes involved in retinal diseases are expressed only in the retina.

After making the discovery, the South African researchers contacted Dr. Sly’s lab, which had done extensive independent work with the gene. Dr. Sly’s group set out to discover how the mutation could cause blindness.

They discovered it interferes with a process necessary for healthy cell development. The mutation causes a secretory protein in the capillaries beneath the retina to improperly “fold,” a process necessary for healthy cell development. When the proteins fail to fold quickly enough, a response is triggered that can cause the cells to die.

“These capillaries nourish the retina,” Dr. Sly said. “When they die, the retina dies along with them.”

Understanding this mechanism should lead directly to the development of new treatments, he said. “If we can find a way to make the proteins fold properly, we should be able to treat the disease. This is very promising.”

Other Saint Louis University researchers participating in the study included Drs. Giuseppe Bonapace, Abdul Waheed and Gul N. Shah.