PMID- 22974557 OWN - NLM STAT- MEDLINE DCOM- 20130121 LR - 20220317 IS - 1090-2430 (Electronic) IS - 0014-4886 (Linking) VI - 238 IP - 2 DP - 2012 Dec TI - Electrical stimulation ameliorates light-induced photoreceptor degeneration in vitro via suppressing the proinflammatory effect of microglia and enhancing the neurotrophic potential of Muller cells. PG - 192-208 LID - S0014-4886(12)00338-X [pii] LID - 10.1016/j.expneurol.2012.08.029 [doi] AB - Many types of electrical stimulation (ES) devices have been shown to promote the survival of degenerated neural cells, such as dopaminergic neurons in the medial forebrain bundle-transected rats, ischemic-injured cortical neurons and inner-and outer-nuclear-layer cells in degenerated retina. Using a rat photic injury model, our lab previously proved the neuroprotective effect of transcorneal electrical stimulation (TCES) on apoptotic photoreceptor cells. To delineate the mechanisms that might underlie this process, the effects of ES on light-damaged photoreceptor degeneration-induced microglia and Muller cell activation were investigated in the present in vitro study. Our data showed that ES (3 ms, 20 Hz, 300-1600 muA) increased survival among light-reared cone-derived cells (661W) cultured alongside microglia or Muller cells analyzed by LDH and TUNEL assays. The degree of rescue was found to depend on the different intensities of the ES current. The immunocytochemistry revealed that ES significantly decreased the numbers of activated microglia cells with ameboid shapes and increased the numbers of reactive gliotic Muller cells with larger soma when they were co-cultured with light-damaged 661W cells. Real-time RT-PCR and Western blotting indicated that ES which was applied to different co-cultures and 661W cell-conditioned media (661WCM)-treated glia cultures had a prominent inhibitive effect on the secretion of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in microglia and a positive regulative effect on the production of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) in Muller cells. The death rate of light-exposed 661W cells cultured with microglia was decreased significantly by the addition of neutralizing antibodies against IL-1beta and TNF-alpha. On the other hand, the death rate of light-exposed 661W cells cultured with Muller cells was prominently increased when the co-culture was incubated in the presence of neutralizing antibody against BDNF while anti-CNTF neutralizing antibody did not induce additional exacerbation of the cell death among those 661W cells. These findings indicate the feasibility of using ES to create a nurturing environment for light-damaged photoreceptor cells. This environment is characterized by diminished microglial activation and fortified Muller cells reactive gliosis, which may have great potential in ameliorating photoreceptor damage. In this way, ES was here determined to be a novel, potent therapeutic option for delaying the progression of photoreceptor degeneration in patients suffering from retinitis pigmentosa (RP). CI - Copyright (c) 2012 Elsevier Inc. All rights reserved. FAU - Zhou, Wen-ting AU - Zhou WT AD - Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 Fen Yang Road, Shanghai 200031, People's Republic of China. FAU - Ni, Ying-qin AU - Ni YQ FAU - Jin, Zi-bing AU - Jin ZB FAU - Zhang, Meng AU - Zhang M FAU - Wu, Ji-hong AU - Wu JH FAU - Zhu, Ying AU - Zhu Y FAU - Xu, Ge-zhi AU - Xu GZ FAU - Gan, De-kang AU - Gan DK LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120910 PL - United States TA - Exp Neurol JT - Experimental neurology JID - 0370712 RN - 0 (Aif1 protein, mouse) RN - 0 (Antigens, CD) RN - 0 (Calcium-Binding Proteins) RN - 0 (Culture Media, Conditioned) RN - 0 (Cytokines) RN - 0 (Ectodysplasins) RN - 0 (Eda protein, mouse) RN - 0 (Microfilament Proteins) RN - 0 (Nerve Growth Factors) RN - 0 (RNA, Messenger) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) SB - IM MH - Analysis of Variance MH - Animals MH - Animals, Newborn MH - Antigens, CD/genetics/metabolism MH - Apoptosis/radiation effects MH - Calcium-Binding Proteins/genetics/metabolism MH - Cell Survival/radiation effects MH - Cells, Cultured MH - Coculture Techniques MH - Culture Media, Conditioned/pharmacology MH - Cytokines/metabolism MH - Ectodysplasins/genetics/metabolism MH - Electric Stimulation/*methods MH - Gene Expression Regulation/drug effects/radiation effects MH - In Situ Nick-End Labeling MH - L-Lactate Dehydrogenase/metabolism MH - Light/*adverse effects MH - Microfilament Proteins/genetics/metabolism MH - Microglia/drug effects/*physiology MH - Nerve Growth Factors/metabolism/*therapeutic use MH - Photoreceptor Cells, Vertebrate/pathology/radiation effects MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Retina/cytology MH - Retinal Degeneration/*etiology/*therapy MH - Time Factors EDAT- 2012/09/15 06:00 MHDA- 2013/01/23 06:00 CRDT- 2012/09/15 06:00 PHST- 2012/01/07 00:00 [received] PHST- 2012/08/28 00:00 [revised] PHST- 2012/08/28 00:00 [accepted] PHST- 2012/09/15 06:00 [entrez] PHST- 2012/09/15 06:00 [pubmed] PHST- 2013/01/23 06:00 [medline] AID - S0014-4886(12)00338-X [pii] AID - 10.1016/j.expneurol.2012.08.029 [doi] PST - ppublish SO - Exp Neurol. 2012 Dec;238(2):192-208. doi: 10.1016/j.expneurol.2012.08.029. Epub 2012 Sep 10.