Gene transfer restores vision to blind chicks

A paper by Williams, et al, published online today in the Public Library of Science-Medicine, desribes how the in ovo delivery of a gene restored vision to blind chickens.

The researchers, led by Susan Semple-Rowland of the University of Florida, carried out their work on a type of Rhode Island Red chicken which carries a genetic mutation making it blind at hatching. This organism provides an experimental model which closely resembles a human disorder called Leber's congenital amaurosis (LCA) type 1.

LCA is a group of retinal disorders that are a common cause of inherited blindness in infants and children. Several types of LCA are caused by mutations in the GUCY2D gene, which encodes retinal guanylate cyclase-1, an enzyme involved in phototransduction (the conversion of light energy into electrical impulses).   

Using fine glass needles, Semple-Rowland and her team injected a lentivirus-based vector carrying the GUCY2D gene through the eggshell into the developing nervous system of early-stage Rhode Island Red chicken embryos.

"The process sounds straightforward but it really isn't," said Semple-Rowland. "It took quite a long time to build the vector, develop the injection procedure and figure out how to hatch the eggs. By doing the injection early during development, we actually treat the cells before they become photoreceptors."   Subsequent behavioural tests showed that vision had been restored in six out of seven of the birds, as a result of transfer of the GUCY2D gene, and electrophysiological analyses showed that retinal cells from the chicks were responsive to light.

"The vision capabilities of the treated animals far exceeded our expectations," says Semple-Rowland,  who is an associate professor of neuroscience at the University of Florida's McKnight Brain Institute.  

The work shows that, at least in principle, a similar treatment may be developed for humans. Children with LCA are not born blind but experience gradual degeneration of the retina. A future treatment would involve an injection of vectors directly into the eyeball during the first few years of life. 

Semple-Rowland is optimistic about the development of such a treatment, saying that "the first treatments for some of these genetic eye diseases [will be available] soon."

Microbubbles deliver insulin gene to pancreas

Baylor University Medical Center researchers have developed a new technique to deliver the insulin gene to the pancreas. The method could lead to a new treatment for type I diabetes.

Insulin is a hormome produced by beta cells in the pancreas and secreted into the bloodstream. Cells in the body have receptors on their surface, which bind to insulin molecules circulating in the bloodstream. Upon activation, insulin receptors mediate the absorption of glucose (sugar) by cells. Glucose taken up from the bloodstream in this way is broken down inside cells to provide them with energy.

In type I, or insulin-dependent, diabetes, pancreatic beta cells are destroyed, in most cases by an autoimmune reaction. As a result, insulin production is severly reduced or stopped altogether, and blood sugar levels can get dangerously high.       

Paul Grayburn and his team used the method of ultrasound-targeted microbubble destruction (UTMD) to successfully deliver insulin genes to the pancreas of rats, and showed that this caused a decrease in blood sugar levels.

Tiny gas-filled bubbles coated with DNA encoding the insulin gene were injected into the bloodstream of rats. Beams of ultrasound were then directed at the Islets of Langerhans, the region of the pancreas containing the insulin-producing beta cells. This caused the microbubbles in nearby blood vessels to burst, releasing the insulin gene. The ultrasound beams also created pores in the beta cell membranes, through which the DNA could enter. 

"Not only was their blood sugar lowered, but there was no evidence of any damage to the pancreas," says Grayburn. Traces of insulin were still detected in the rats' bloodtreams up to 3 weeks after introduction of the gene into the pancreas. If this timescale can be increased, the UTMD technique may provide a powerful new treatment for Type I diabetics, who have to take daily injections of insulin to maintain low blood glucose levels.

"Our ultimate goal," says Grayburn, "is to research the regeneration of insulin-producing cells in patients with diabetes."