title: N-Acetylcysteine promotes long-term survival of cones in a model of retinitis pigmentosa.
abstract: Retinitis pigmentosa (RP) is a major source of blindness caused by a large variety of mutations that lead to the death of rod photoreceptors. After rods die, cones gradually die from progressive oxidative damage. Several types of antioxidant formulations have been shown to reduce cone cell death over a relatively short-time frame, but in order for this strategy to be translated into a new treatment for patients with RP, prolonged effects will be needed. In this study, we determined that orally administered N-acetylcysteine (NAC) reduced cone cell death and preserved cone function by reducing oxidative damage in two models of RP, rd1(+/+) and rd10(+/+) mice. In rd10(+/+) mice, supplementation of drinking water with NAC promoted partial maintenance of cone structure and function for at least 6 months. Topical application of NAC to the cornea also reduced superoxide radicals in the retina and promoted survival and functioning of cones. Since oral and/or topical administration of NAC is feasible for long-term treatment in humans, and NAC has a good safety profile, it is reasonable to consider clinical trials to evaluate the effects of prolonged treatment with NAC in patients with RP.
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Lee
authors.forename: Shinichi
authors.initials: S
authors.lastname: Usui
authors.forename: Abu-Bakr
authors.initials: AB
authors.lastname: Zafar
authors.forename: Brian C
authors.initials: BC
authors.lastname: Oveson
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Jo
authors.forename: Lili
authors.initials: L
authors.lastname: Lu
authors.forename: Solmaz
authors.initials: S
authors.lastname: Masoudi
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival; D004195:Disease Models, Animal; D004596:Electroretinography; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects; D010775:Photic Stimulation; D017949:Retinal Cone Photoreceptor Cells / Q000187:drug effects* / Q000473:pathology; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D000099156:Superoxide Dismutase 2
chemical_list: D000111:Acetylcysteine; D000975:Antioxidants; D002374:Catalase; D013482:Superoxide Dismutase; D013481:Superoxides; D000099156:Superoxide Dismutase 2