Studies in a mouse model suggest that an orally active antioxidant, N-acetylecysteine (NAC), may be beneficial in the treatment of retinitis pigmentosa.
In a previous study, Dr. Campochiaro and colleagues determined that after rods die in RP, the cones undergo progressive oxidative damage and gradual cell death. When the rods die, oxygen consumption in the retina dramatically decreases, the oxygen level in the outer retina goes up, and the cones are exposed to high tissue levels of oxygen, which causes oxidative damage.
"We've determined that if mice with RP are given various antioxidants, the cone cell death can be substantially reduced, and the cone function can be preserved," Dr. Campochiaro said.
Previous work was done with mixtures that were injected intraperitoneally on a daily basis. However, NAC is an appealing alternative because it can be given orally in drinking water. In addition, it can be given orally in humans and has already been approved for use in cases of acetaminophen overdose. This means that NAC can be used in clinical trials of RP due to its prior approval and favorable toxicity profile, Dr. Campochiaro said.
In the recent study, which was presented at the annual meeting of the Association for Research in Vision and Ophthalmology, 7 mg/ml of NAC was administered in the drinking water of Rd10+/+ mice; a control group did not receive NAC. Some mice were given a regular diet, while others were given a diet supplemented with vitamins C and E and α-lipoic acid.
"We found that NAC was able to reduce oxidative damage in the cones and reduce cone cell death," Dr. Campochiaro said. "And because we could give it orally, we could give it for a prolonged period.
"We found that even up to 6 months, which is a very long time in a mouse, we were able to reduce the cone cell death significantly and preserve photopic ERGs, which is a measure of cone function," he added.
The mice given drinking water containing NAC had mean photopic b-wave amplitudes that were roughly double those of untreated mice at P60, P120, and P180.
Before conducting the study with NAC, Dr. Campochiaro and colleagues evaluated many other antioxidants and had demonstrated that various mixtures of antioxidants could help to preserve cone function and survival. NAC seemed to be particularly effective and worked for a long time, while other compounds could not be tested over extended periods because they required daily injections.
The researchers also observed that the cones were protected in transgenic mice that express various components of the endogenous antioxidant defense system. Adding NAC to the drinking water of these mice produced an additive effect.
"We can get an additional effect from combining these two treatment approaches, so it suggests that in the future we could consider gene transfer to increase the expression of components of the antioxidant defense system combined with oral treatment with NAC or a compound like NAC," Dr. Campochiaro said.
"We're very interested in moving on into clinical trials, but that's going to take some preliminary work to determine which patient population would be the best to study," he concluded. "But the work is very exciting."
Peter A. Campochiaro, MDPhone: 410/955-5106
Dr. Campochiaro does not have any commercial relationships to report.