N-acetylcysteine suppresses retinal detachment in an experimental model of proliferative vitreoretinopathy.
Proliferative vitreoretinopathy (PVR) is a complication that develops in 5% to 10% of patients who undergo surgery to correct a detached retina. The only treatment option for PVR is surgical intervention, which has a limited success rate that diminishes in patients with recurring PVR. Our recent studies revealed that antioxidants prevented intracellular signaling events that were essential for experimental PVR. The purpose of this study was to test whether N-acetyl-cysteine (NAC), an antioxidant used in a variety of clinical settings, was capable of protecting rabbits from PVR. Vitreous-driven activation of PDGFRalpha and cellular responses intrinsic to PVR (contraction of collagen gels and cell proliferation) were blocked by concentrations of NAC that were well below the maximum tolerated dose. Furthermore, intravitreal injection of NAC effectively protected rabbits from developing retinal detachment, which is the sight-robbing phase of PVR. Finally, these observations with an animal model appear relevant to clinical PVR because NAC prevented human PVR vitreous-induced contraction of primary RPE cells derived from a human PVR membrane. Our observations demonstrate that antioxidants significantly inhibited experimental PVR, and suggest that antioxidants have the potential to function as a PVR prophylactic in patients undergoing retinal surgery to repair a detached retina.
Lei
Hetian
H
Department of Ophthalmology, Schepens Eye Research Institute, Harvard Medical School, 20 Staniford St, Boston, MA 02114, USA.
Velez
Gisela
G
Cui
Jing
J
Samad
Arif
A
Maberley
David
D
Matsubara
Joanne
J
Kazlauskas
Andrius
A
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D012163:Retinal Detachment / Q000150:complications / Q000517:prevention & control* / Q000601:surgery; D055213:Retinal Pigment Epithelium / Q000166:cytology; D018630:Vitreoretinopathy, Proliferative / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D014822:Vitreous Body / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D000111:Acetylcysteine