title: Transcorneal electrical stimulation promotes survival of retinal ganglion cells after optic nerve transection in rats accompanied by reduced microglial activation and TNF-α expression.
abstract: Microglial activation plays a crucial role in the pathological processes of various retinal and optic nerve diseases. TNF-α is a pro-inflammatory cytokine that is rapidly upregulated and promotes retinal ganglion cells (RGCs) death after optic nerve injury. However, the cellular source of TNF-α after optic nerve injury remains unclear. Thus, we aimed to determine the changes of retinal microglial activation in a rat model of optic nerve transection (ONT) after transcorneal electrical stimulation (TES). Furthermore, we assessed TNF-α expression after ONT and evaluated the effects of TES on TNF-α production. Rats were divided into 2 control groups receiving a sham surgery procedure, 2 ONT+Sham TES groups, and 2 ONT+TES groups. The rats were sacrificed on day 7 or 14 after ONT. RGCs were retrogradely labelled by Fluorogold (FG) 7 days before ONT, one TES group and corresponding controls were stimulated on day 0, 4, and the second were stimulated on day 0, 4, 7, 10. Whole-mount immunohistofluorescence, quantification of RGCs and microglia, and western blot analysis were performed on day 7 and 14 after ONT. TES significantly increased RGCs survival on day 7 and 14 after ONT, which was accompanied by reduced microglia on day 7, but not 14. TNF-α was co-localized with ameboid microglia and significantly increased on day 7 and 14 after ONT. TES significantly reduced TNF-α production on day 7 and 14 after ONT. Our study demonstrated that TES promotes RGCs survival after ONT accompanied by reduced microglial activation and microglia-derived TNF-α production.
authors: Department of Neurology, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
authors: Houmin
authors: H
authors: Yin
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors: Houfa
authors: H
authors: Yin
authors: Department of Orthopedics, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China.
authors: Wei
authors: W
authors: Zhang
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors: Qi
authors: Q
authors: Miao
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors: Zhenwei
authors: Z
authors: Qin
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors: Shenchao
authors: S
authors: Guo
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors: Qiuli
authors: Q
authors: Fu
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors: Jian
authors: J
authors: Ma
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors: Fang
authors: F
authors: Wu
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors: Jinfu
authors: J
authors: Yin
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China.
authors: Yabo
authors: Y
authors: Yang
authors: Eye Center, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China; Zhejiang Provincial Key Laboratory of Ophthalmology, Hangzhou, Zhejiang Province, China. Electronic address: xiaoyunfang@zju.edu.cn.
authors: Xiaoyun
authors: X
authors: Fang
mesh_terms: D000818:Animals; D019771:Axotomy / Q000379:methods; D002452:Cell Count; D002470:Cell Survival / Q000502:physiology; D003315:Cornea; D004558:Electric Stimulation; D004599:Electric Stimulation Therapy / Q000379:methods; D008297:Male; D017628:Microglia / Q000378:metabolism; D009900:Optic Nerve / Q000502:physiology; D020221:Optic Nerve Injuries / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D015854:Up-Regulation
chemical_list: D014409:Tumor Necrosis Factor-alpha
keywords: Microglial activation; Optic nerve; Retinal ganglion cells; TNF-α; Transcorneal electrical stimulation