Blocking oxidative stress may reduce cone cell death in RP

Fort Lauderdale, FL-In retinitis pigmentosa (RP), damage to the cones occurs after death of the rods, said Peter A. Campochiaro, MD. The George S. and Dolores Doré Eccles Professor of Ophthalmology and Neuroscience, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, proposed a hypothesis explaining the death of cone cells in this disease.

“[RP] is a label for a group of diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by a gradual death of the cones,” he said. “Rods are a major source of oxygen utilization in the retina, and after rods die, the level of oxygen in the outer retina is increased resulting in progressive oxidative and nitrosative damage to cones.”

The mechanism of cone cell death in RP begins with the dead of rod cells after exposure to increased levels of oxygen. After rod death the oxidation in the outer retina increases. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is activated, leading to the production of superoxide radicals and generation of other reactive oxygen species. Because of the high endogenous levels of nitric oxide, the superoxide radicals interact with nitric oxide and form peroxynitrite. There is then subsequent gradual oxidative damage to lipids, proteins, and DNA in the cells, with the end result being cone cell death.

Antioxidants vitamin C, vitamin E, alpha-lipoic acid, NADPH oxidase inhibitor, and nitric oxide synthase inhibitor can reduce cone cell death in models of RP. Oral N-acetylcysteine is another potential treatment that can rescue cone cells for several months.

Gene therapy is the next step to bolster the endogenous antioxidant defense system, Dr. Campochiaro concluded.