Constance Cepko

As Punzo digs deeper into why the cones die, other lab members have been looking for ways to keep the rods alive as well—even nonfunctioning rods might help prevent the death of the cones.

Bo Chen, another postdoctoral fellow, found a potential way to save the rods. Chen found that rods require HDAC4 to survive during development, so he and Cepko decided to try delivering extra HDAC4 to the retinas of mice with retinitis pigmentosa. The strain they studied typically loses all rods about three weeks after birth and their cones over the next few months. Using a method previously developed in the lab, Chen deposited HDAC4 DNA behind the retinas of unconscious mice using a needle a little wider than a hair. He then applied an electric current to enable the DNA to enter the retina. More than two months later, the mice still retained many of their rods and cones. The results appear in the January 9, 2009, issue of Science.

The method Chen used probably would not work on humans—the electric charge might damage parts of the eye. So, he and Cepko are employing the approach used to restore Lancelot's vision: using a harmless virus to deliver the gene to the retina. Eight years after his surgery, the dog can still see. “By just good luck, the virus is still there,” Cepko says.

The team packages the HDAC4 DNA with the virus and delivers it behind the retinas of mice with retinitis pigmentosa; the virus enters the cells on its own.

Cepko is heartened by the work of researchers at the University of Pennsylvania School of Medicine. A year ago, they gave patients with the same genetic defect as Lancelot's—a mutation that causes Leber congenital amaurosis—the therapy that helped the dog. For some of these patients, vision has improved.

Photo: Jason Grow

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