N-acetylcysteine amide (NACA) prevents retinal degeneration by up-regulating reduced glutathione production and reversing lipid peroxidation.

Abstract

Oxidative stress plays a critical role in accelerating retinal pigment epithelial dysfunction and death in degenerative retinal diseases, including age-related macular degeneration. Given the key role of oxidative stress-induced retinal pigment epithelial cell death and secondary photoreceptor loss in the pathogenesis of age-related macular degeneration, we hypothesized that a novel thiol antioxidant, N-acetylcysteine amide (NACA), might ameliorate cellular damage and subsequent loss of vision. Treatment of human retinal pigment epithelial cells with NACA protected against oxidative stress-induced cellular injury and death. NACA acted mechanistically by scavenging existing reactive oxygen species while halting production of reactive oxygen species by reversing lipid peroxidation. Furthermore, NACA functioned by increasing the levels of reduced glutathione and the phase II detoxification enzyme glutathione peroxidase. Treatment of mice exposed to phototoxic doses of light with NACA maintained retinal pigment epithelial cell integrity and prevented outer nuclear layer cell death as examined by histopathologic methods and rescued photoreceptor function as measured by electroretinography. These observations indicate that NACA protects against oxidative stress-induced retinal pigment epithelial and photoreceptor cell death in vitro and in vivo. The data suggest that NACA may be a novel treatment in rescuing retinal function and preventing vision loss secondary to retinal degenerative diseases, including age-related macular degeneration.

• Authors: Andrew M Schimel, Linu Abraham, Douglas Cox, Abdoulaye Sene, Courtney Kraus, Dru S Dace, Nuran Ercal, Rajendra S Apte
• Journal: The American journal of pathology (Am J Pathol) Vol. 178 Issue 5 Pg. 2032-43 (May 2011) ISSN: 1525-2191 [Electronic] United States
• PMID: 21457933 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Free Radical Scavengers
• N-Acetylcysteinamide
• Glutathione
• Acetylcysteine

Topics

• Acetylcysteine (analogs & derivatives, pharmacology)
• Animals
• Antioxidants (pharmacology)
• Cells, Cultured
• Free Radical Scavengers (pharmacology)
• Glutathione (biosynthesis)
• Humans
• Lipid Peroxidation (drug effects)
• Mice
• Oxidative Stress (drug effects)
• Retinal Degeneration (metabolism, prevention & control)
• Retinal Pigment Epithelium (drug effects, metabolism)