||Last Updated: Nov 12th, 2006 - 20:38:00
Development in mice offers hope for treatment of certain eye diseases
Scientists at Johns Hopkins have successfully blocked the advance of retinal degeneration in mice with a form of retinitis pigmentosa (RP) by treating them with vitamin E, alpha-lipoic acid and other antioxidant chemicals.
"Much more work needs to be done to determine if what we did in mice will work in humans," said Peter Campochiaro, the Eccles Professor of Ophthalmology and Neuroscience at The Johns Hopkins University School of Medicine. "But these findings have helped to solve a mystery."
In patients with RP, rod photoreceptors die from a mutation, but it has not been known why cone photoreceptors die. After rods die, the level of oxygen in the retina goes up, and this work shows that it is the high oxygen that gradually kills the cones. Oxygen damage is also called "oxidative damage" and can be reduced by antioxidants. So for the first time, scientists have a treatment target in patients with RP, added Campochiaro. His team's findings appeared in the July online edition of the Proceedings of the National Academy of Sciences.
Retinas in all mammals, from mouse to man, are made up of light-sensitive cells known as cones and rods, named for their shapes, which convert light into nerve signals that are then transmitted to the brain via the optic nerve. Cones are needed to see colors and make vision possible in bright light, whereas the far more numerous rods permit sight in low light. The human retina contains approximately 125 million rod cells and six million cone cells. In diseases like RP and age-related macular degeneration (AMD), these cells die off and eventually lead to blindness (in the case of RP) or legal blindness (in the case of AMD).
In earlier studies exposing mice to pure oxygen, the Hopkins scientists found that high levels of oxygen in the retina killed both rods and cones, said Campochiaro. "This was the clue that the high oxygen levels that occur naturally in the retina after rods die was the suspect regarding cone cell death. To test this, we used antioxidants, which protect cells from oxygen damage, and since they allowed many more cones to survive, it proves that the suspect is guilty."
In this mouse model of retinal degeneration, the rods have completely degenerated by the 18th day of age, and then the cones start to degenerate, with 85 percent of them dying off by the time the mice are 35 days old. Campochiaro and his team injected vitamin E, vitamin C, alpha-lipoic acid or an antioxidant similar to superoxide dismutase between the 18th and 35th day. In mice that received vitamin E or alpha-lipoic acid, 40 percent of the cones survived, about twice as many as in the control group or the groups treated with the other antioxidants, which had no identifiable effect.
"What's clear is the link between oxygen and photoreceptor damage, as well as the potential of antioxidant treatment," Campochiaro said. "These experiments suggest that an optimized regimen of antioxidants may help to protect patients with retinitis pigmentosa."
Campochiaro emphasized that even if found valuable, antioxidant treatment of RP, a group of inherited blinding diseases with complex genetic roots, would not cure the disease. But the salvaging of cones, which are concentrated in the retina's macula and are critical to central vision, could serve as a "maintenance therapy," he said. "That alone would be an enormous help."
RP affects only about 100,000 people in the United States. But the oxygen damage has also been implicated in other more pervasive eye diseases, like AMD and cataracts.
Antioxidants naturally occur in some fruits and vegetables, and are available as supplements, but Campochiaro said it remains unclear whether the amounts of antioxidants consumed in foods provided any benefit to people with these types of vision impairments.
The funding for this study was provided by the Macula Vision Research Foundation, as well as gifts from Dr. and Mrs. William Lake, and Mrs. Susan Meyers. Co-authors of the study included Keiichi Komeima, Brian Rogers and Lili Lu, all of the Johns Hopkins School of Medicine.
Contact: Jeff Ventura
Johns Hopkins Medical Institutions
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