title: Evaluation of the toxicity of graphene oxide exposure to the eye.
abstract: Graphene and its derivatives are the new carbon nanomaterials with the prospect for great applications in electronics, energy storage, biosensors and medicine. However, little is known about the toxicity of graphene or its derivatives in the case of occasional or repeated ocular exposure. We performed in vitro and in vivo studies to evaluate the toxicity of graphene oxide (GO) exposure to the eye. Primary human corneal epithelium cells (hCorECs) and human conjunctiva epithelium cells (hConECs) were exposed to GO (12.5-100 μg/mL). Acute GO exposure (2 h) did not induce cytotoxicity to hCorECs. However, short-term GO exposure (24 h) exerted significant cytotoxicity to hCorECs and hConECs with increased intracellular reactive oxygen species (ROS). Glutathione (GSH) reduced the GO-induced cytotoxicity. We further performed acute eye irritation tests in albino rabbits according to the Organization for Economic Cooperation and Development (OECD) guidelines, and the rabbits did not exhibit corneal opacity, conjunctival redness, abnormality of the iris, or chemosis at any time point after the instillation of 100 μg/mL of GO. However, 5-day repeated GO exposure (50 and 100 μg/mL) caused reversible mild corneal opacity, conjunctival redness and corneal epithelium damage to Sprague-Dawley rats, which was also alleviated by GSH. Therefore, our study suggests that GO-induced time- and dose-dependent cytotoxicity to hCorECs and hConECs via oxidative stress. Occasional GO exposure did not cause acute eye irritation; short-term repeated GO exposure generally resulted in reversible damage to the eye via oxidative stress, which may be alleviated by the antioxidant GSH.
authors.affiliation: a Southwest Hospital/Southwest Eye Hospital, Third Military Medical University , Chongqing , China .|b Key Lab of Visual Damage and Regeneration & Restoration of Chongqing , Chongqing , China , and.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: c Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Liang
authors.initials: L
authors.lastname: Yan
authors.affiliation: a Southwest Hospital/Southwest Eye Hospital, Third Military Medical University , Chongqing , China .|b Key Lab of Visual Damage and Regeneration & Restoration of Chongqing , Chongqing , China , and.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: a Southwest Hospital/Southwest Eye Hospital, Third Military Medical University , Chongqing , China .|b Key Lab of Visual Damage and Regeneration & Restoration of Chongqing , Chongqing , China , and.
authors.forename: Yijian
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Southwest Hospital/Southwest Eye Hospital, Third Military Medical University , Chongqing , China .|b Key Lab of Visual Damage and Regeneration & Restoration of Chongqing , Chongqing , China , and.
authors.forename: Qiyou
authors.initials: Q
authors.lastname: Li
authors.affiliation: a Southwest Hospital/Southwest Eye Hospital, Third Military Medical University , Chongqing , China .|b Key Lab of Visual Damage and Regeneration & Restoration of Chongqing , Chongqing , China , and.
authors.forename: Siyu
authors.initials: S
authors.lastname: Chen
authors.affiliation: a Southwest Hospital/Southwest Eye Hospital, Third Military Medical University , Chongqing , China .|b Key Lab of Visual Damage and Regeneration & Restoration of Chongqing , Chongqing , China , and.
authors.forename: Yuli
authors.initials: Y
authors.lastname: Yang
authors.affiliation: c Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences , Beijing , China.
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Gu
authors.affiliation: a Southwest Hospital/Southwest Eye Hospital, Third Military Medical University , Chongqing , China .|b Key Lab of Visual Damage and Regeneration & Restoration of Chongqing , Chongqing , China , and.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Xu
authors.affiliation: a Southwest Hospital/Southwest Eye Hospital, Third Military Medical University , Chongqing , China .|b Key Lab of Visual Damage and Regeneration & Restoration of Chongqing , Chongqing , China , and.
authors.forename: Zheng Qin
authors.initials: ZQ
authors.lastname: Yin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology; D005123:Eye / Q000187:drug effects* / Q000473:pathology; D005128:Eye Diseases / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006108:Graphite / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D049329:Nanostructures / Q000737:chemistry / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D010087:Oxides; D061251:Primary Cell Culture; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013499:Surface Properties
chemical_list: D000975:Antioxidants; D010087:Oxides; D017382:Reactive Oxygen Species; D006108:Graphite; D005978:Glutathione
keywords: Environmental toxicology; exposure; nanotoxicology; occupational health; toxicology