title: Dose-dependent protective effect of lithium chloride on retinal ganglion cells is interrelated with an upregulated intraretinal BDNF after optic nerve transection in adult rats.
abstract: Neuroprotection of lithium for axotomized retinal ganglion cells (RGCs) is attributed to upregulated intraretinal Bcl-2. As lithium also upregulates brain-derived neurotrophic factor (BDNF) which can rescue axotomized RGCs, it is hypothesized that lithium could protect RGCs through BDNF. This study investigated this hypothesis and a possible relationship between the dose and protection of lithium. All adult experimental rats received daily intraperitoneal injections of lithium chloride (LiCl) at 30, 60 or 85 mg/kg·bw until they were euthanized 2, 7 or 14 days after left intraorbital optic nerve (ON) transection. Our results revealed that RGC densities promoted and declined with increased dose of LiCl and the highest RGC densities were always in the 60 mg/kg·bw LiCl group at both 7 and 14 day points. Similar promotion and decline in the mRNA and protein levels of intraretinal BDNF were also found at the 14 day point, while such BDNF levels increased in the 30 mg/kg·bw LiCl group but peaked in the 60 and 85 mg/kg·bw LiCl groups at the 7 day point. These findings suggested that lithium can delay the death of axotomized RGCs in a dose-dependent manner within a certain period after ON injury and such beneficial effect is interrelated with an upregulated level of intraretinal BDNF.
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, Xi'an 710032, China. wumm33@hotmail.com.
authors.forename: Ming-Mei
authors.initials: MM
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, General Hospital of Beijing Military Region, Beijing 100700, China. zhutingting85@163.com.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, General Hospital of Beijing Military Region, Beijing, 100700, China. wpfmmu@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, Xi'an 710032, China. kuangf@fmmu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Kuang
authors.affiliation: Department of Spine Surgery, Xi'an Red Cross Hospital, Xi'an 710054, China. haodingjun@126.com.
authors.forename: Ding-Jun
authors.initials: DJ
authors.lastname: Hao
authors.affiliation: Institute of Neurosciences, The Fourth Military Medical University, Xi'an 710032, China. yousiwei@fmmu.edu.cn.
authors.forename: Si-Wei
authors.initials: SW
authors.lastname: You
authors.affiliation: Department of Ophthalmology, General Hospital of Beijing Military Region, Beijing 100700, China. liyaoyu63@sina.com.
authors.forename: Yao-Yu
authors.initials: YY
authors.lastname: Li
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D018021:Lithium Chloride / Q000494:pharmacology*; D020221:Optic Nerve Injuries / Q000378:metabolism / Q000473:pathology; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D020011:Protective Agents; D012333:RNA, Messenger; D018021:Lithium Chloride
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