Login Register Cart 0
Research Article

过表达神经保护蛋白 PEDF 和 GM-CSF 的人视网膜色素上皮细胞治疗神经视网膜变性

卷 22, 期 2, 2022

发表于: 07 July, 2021

页: [168 - 183] 页: 16

弟呕挨: 10.2174/1566523221666210707123809

价格: $65

摘要

背景：非病毒转座子介导的基因传递可以克服病毒载体的局限性。转座子基因传递提供了色素上皮衍生因子 (PEDF) 和粒细胞-巨噬细胞集落刺激因子 (GM-CSF) 等基因的安全和终生表达，以通过减少氧化应激损伤来对抗视网膜变性。 目的：本研究旨在利用睡美人转座子转染具有神经保护因子PEDF和GM-CSF的人视网膜色素上皮（RPE）细胞，探讨这些因子对氧化应激损伤的影响。 方法：使用高活性睡美人转座子基因传递系统 (SB100X)，通过电穿孔将人 RPE 细胞转染 PEDF 和 GM-CSF。通过 RT-qPCR 确定基因表达，通过蛋白质印迹和 ELISA 确定蛋白质水平。通过测量人 RPE 细胞中抗氧化剂谷胱甘肽的浓度，并对暴露于 H2O2 的大鼠视网膜组织培养物 (ROC) 的视网膜完整性、炎症和细胞凋亡进行免疫组织化学检查，确定了蛋白质的细胞应激水平和神经保护作用. 结果：人 RPE 细胞被有效转染，显示出显着增强的基因表达和蛋白质分泌。与未转染/未处理的对照相比，过表达 PEDF 和/或 GM-CSF 或用重组蛋白预处理的人类 RPE 细胞在 H2O2 孵育后表现出显着增加的谷胱甘肽水平。 rPEDF 和/或 rGM-CSF 处理的 ROC 表现出炎症反应和细胞退化减少。 结论： 结合使用 SB100X 和电穿孔可以成功地将 GM-CSF 和/或 PEDF 递送至 RPE 细胞。 PEDF 和/或 GM-CSF 减少了 RPE 细胞和 ROC 中 H2O2 介导的氧化应激损伤，为重建细胞保护环境以阻止与年龄相关的视网膜变性提供了令人鼓舞的技术。

关键词: 睡美人转座子、PEDF、GM-CSF、老年性黄斑变性、RPE细胞、非病毒基因传递、氧化应激损伤、眼部基因治疗

« Previous Next »
图形摘要

[1]
NIH. Available from: https://nei.nih.gov/learn-about-eye-health/resources-for-health-educators/eye-health-data-and-statistics/age-related-macular-degeneration-amd-data-and-statistics [Accessed November 13, 2020]
[2]
Mitchell P, Liew G, Gopinath B, Wong TY. Age-related macular degeneration. Lancet 2018; 392(10153): 1147-59.
[http://dx.doi.org/10.1016/S0140-6736(18)31550-2] [PMID: 30303083]
[3]
Al-Zamil WM, Yassin SA. Recent developments in age-related macular degeneration: A review. Clin Interv Aging 2017; 12: 1313-30.
[http://dx.doi.org/10.2147/CIA.S143508] [PMID: 28860733]
[4]
Sacconi R, Corbelli E, Querques L, Bandello F, Querques G. A review of current and future management of geographic atrophy. Ophthalmol Ther 2017; 6(1): 69-77.
[http://dx.doi.org/10.1007/s40123-017-0086-6] [PMID: 28391446]
[5]
Kumar-Singh R. The role of complement membrane attack complex in dry and wet amd - from hypothesis to clinical trials. Exp Eye Res 2019; 184: 266-77.
[http://dx.doi.org/10.1016/j.exer.2019.05.006] [PMID: 31082363]
[6]
Bascuas T, Kropp M, Harmening N, Asrih M, Izsvák Z, Thumann G. Induction and analysis of oxidative stress in sleeping beauty transposon-transfected human retinal pigment epithelial cells. J Vis Exp 2020; 2020(166): 1-25.
[PMID: 33369607]
[7]
He Y, Leung KW, Ren Y, Pei J, Ge J, Tombran-Tink J. PEDF improves mitochondrial function in RPE cells during oxidative stress. Invest Ophthalmol Vis Sci 2014; 55(10): 6742-55.
[http://dx.doi.org/10.1167/iovs.14-14696] [PMID: 25212780]
[8]
Cao S, Walker GB, Wang X, Cui JZ, Matsubara JA. Altered cytokine profiles of human retinal pigment epithelium: Oxidant injury and replicative senescence. Mol Vis 2013; 19: 718-28.
[PMID: 23559866]
[9]
Farnoodian M, Sorenson CM, Sheibani N. PEDF expression affects the oxidative and inflammatory state of choroidal endothelial cells. Am J Physiol Cell Physiol 2018; 314(4): C456-72.
[http://dx.doi.org/10.1152/ajpcell.00259.2017] [PMID: 29351407]
[10]
Polato F, Becerra SP. Retinal degenerative diseases: Mechanisms and experimental therapies. Retinal Degenerative Diseases. 2016; pp. 699-706.
[http://dx.doi.org/10.1007/978-1-4614-3209-8]
[11]
Schallenberg M, Charalambous P, Thanos S. GM-CSF regulates the ERK1/2 pathways and protects injured retinal ganglion cells from induced death. Exp Eye Res 2009; 89(5): 665-77.
[http://dx.doi.org/10.1016/j.exer.2009.06.008] [PMID: 19560459]
[12]
Schallenberg M, Charalambous P, Thanos S. GM-CSF protects rat photoreceptors from death by activating the SRC-dependent signalling and elevating anti-apoptotic factors and neurotrophins. Graefes Arch Clin Exp Ophthalmol 2012; 250(5): 699-712.
[http://dx.doi.org/10.1007/s00417-012-1932-9] [PMID: 22297538]
[13]
Tombran-Tink J, Barnstable CJ. PEDF: A multifaceted neurotrophic factor. Nat Rev Neurosci 2003; 4(8): 628-36.
[http://dx.doi.org/10.1038/nrn1176] [PMID: 12894238]
[14]
Tombran-Tink J. The neuroprotective and angiogenesis inhibitory serpin, PEDF: New insights into phylogeny, function, and signaling. Front Biosci 2005; 10: 2131-49.
[http://dx.doi.org/10.2741/1686] [PMID: 15970483]
[15]
Bilak MM, Corse AM, Bilak SR, Lehar M, Tombran-Tink J, Kuncl RW. Pigment epithelium-derived factor (PEDF) protects motor neurons from chronic glutamate-mediated neurodegeneration. J Neuropathol Exp Neurol 1999; 58(7): 719-28.
[http://dx.doi.org/10.1097/00005072-199907000-00006] [PMID: 10411342]
[16]
Duh EJ, Yang HS, Suzuma I, et al. Pigment epithelium-derived factor suppresses ischemia-induced retinal neovascularization and VEGF-induced migration and growth. Invest Ophthalmol Vis Sci 2002; 43(3): 821-9.
[PMID: 11867604]
[17]
Gene therapy clinical trials worldwide Available from: http://www.abedia.com/wiley/search.php [Accessed April 19, 2020].
[18]
Hartman ZC, Black EP, Amalfitano A. Adenoviral infection induces a multi-faceted innate cellular immune response that is mediated by the toll-like receptor pathway in A549 cells. Virology 2007; 358(2): 357-72.
[http://dx.doi.org/10.1016/j.virol.2006.08.041] [PMID: 17027060]
[19]
Han IC, Burnight ER, Ulferts MJ, et al. Helper-dependent adenovirus transduces the human and rat retina but elicits an inflammatory reaction when delivered subretinally in rats. Hum Gene Ther 2019; 30(11): 1371-84.
[http://dx.doi.org/10.1089/hum.2019.159] [PMID: 31456426]
[20]
Shirley JL, de Jong YP, Terhorst C, Herzog RW. Immune responses to viral gene therapy vectors. Mol Ther 2020; 28(3): 709-22.
[http://dx.doi.org/10.1016/j.ymthe.2020.01.001] [PMID: 31968213]
[21]
Cavazza A, Moiani A, Mavilio F. Mechanisms of retroviral integration and mutagenesis. Hum Gene Ther 2013; 24(2): 119-31.
[http://dx.doi.org/10.1089/hum.2012.203] [PMID: 23330935]
[22]
Biasco L, Baricordi C, Aiuti A. Retroviral integrations in gene therapy trials. Mol Ther 2012; 20(4): 709-16.
[http://dx.doi.org/10.1038/mt.2011.289] [PMID: 22252453]
[23]
Kuşcu L, Sezer AD. Future prospects for gene delivery systems. Expert Opin Drug Deliv 2017; 14(10): 1205-15.
[http://dx.doi.org/10.1080/17425247.2017.1292248] [PMID: 28165836]
[24]
Hacein-Bey-Abina S, Garrigue A, Wang GP, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest 2008; 118(9): 3132-42.
[http://dx.doi.org/10.1172/JCI35700] [PMID: 18688285]
[25]
Feschotte C, Pritham EJ. DNA transposons and the evolution of eukaryotic genomes. Annu Rev Genet 2007; 41: 331-68.
[http://dx.doi.org/10.1146/annurev.genet.40.110405.090448] [PMID: 18076328]
[26]
Ivics Z, Izsvák Z. The expanding universe of transposon technologies for gene and cell engineering. Mob DNA 2010; 1(1): 25.
[http://dx.doi.org/10.1186/1759-8753-1-25] [PMID: 21138556]
[27]
Yant SR, Meuse L, Chiu W, Ivics Z, Izsvak Z, Kay MA. Somatic integration and long-term transgene expression in normal and haemophilic mice using a DNA transposon system. Nat Genet 2000; 25(1): 35-41.
[http://dx.doi.org/10.1038/75568] [PMID: 10802653]
[28]
Walisko O, Schorn A, Rolfs F, et al. Transcriptional activities of the sleeping beauty transposon and shielding its genetic cargo with insulators. Mol Ther 2008; 16(2): 359-69.
[http://dx.doi.org/10.1038/sj.mt.6300366] [PMID: 18071335]
[29]
Hudecek M, Izsvák Z, Johnen S, Renner M, Thumann G, Ivics Z. Going non-viral: The sleeping beauty transposon system breaks on through to the clinical side. Crit Rev Biochem Mol Biol 2017; 52(4): 355-80.
[http://dx.doi.org/10.1080/10409238.2017.1304354] [PMID: 28402189]
[30]
Zayed H, Izsvák Z, Walisko O, Ivics Z. Development of hyperactive sleeping beauty transposon vectors by mutational analysis. Mol Ther 2004; 9(2): 292-304.
[http://dx.doi.org/10.1016/j.ymthe.2003.11.024] [PMID: 14759813]
[31]
Izsvák Z, Ivics Z, Plasterk RH. Sleeping Beauty, a wide host-range transposon vector for genetic transformation in vertebrates. J Mol Biol 2000; 302(1): 93-102.
[http://dx.doi.org/10.1006/jmbi.2000.4047] [PMID: 10964563]
[32]
Potter H, Heller R. Transfection by electroporation. Curr Protocols Mol Biol. 2018; pp. 9.3.1-9.3.13.
[http://dx.doi.org/10.1002/cpmb.48]
[33]
Shirley SA, Heller R, Heller LC. Electroporation gene therapy, gene therapy of cancer: Translational approaches from preclinical studies to clinical implementation. (3rd),. Elsevier Inc. 2013. [Online]
[http://dx.doi.org/10.2174/156652310791823489]
[34]
Pastor M, Johnen S, Harmening N, et al. The antibiotic-free pfar4 vector paired with the sleeping beauty transposon system mediates efficient transgene delivery in human cells. Mol Ther - Nucleic Acids. 2018; 11: pp. 57-67.
[http://dx.doi.org/10.1016/j.omtn.2017.12.017]
[35]
Johnen S, Djalali-Talab Y, Kazanskaya O, et al. Antiangiogenic and neurogenic activities of sleeping beauty-mediated pedf-transfected rpe cells in vitro and in vivo. Biomed Res Int 2015; 2015: S63845.
[http://dx.doi.org/10.1155/2015/863845] [PMID: 26697494]
[36]
Garcia-Garcia L, Recalde S, Hernandez M, et al. Long-term pedf release in rat iris and retinal epithelial cells after sleeping beauty transposon-mediated gene delivery. Mol Ther - Nucleic Acids 2017; 9: 1-11.
[http://dx.doi.org/10.1016/j.omtn.2017.08.001]
[37]
Thumann G, Harmening N, Prat-Souteyrand C, et al. Engineering of pedf-expressing primary pigment epithelial cells by the sb transposon system delivered by pfar4 plasmids. Mol Ther - Nucleic Acids. 2017; 6: pp. 302-14.
[http://dx.doi.org/10.1016/j.omtn.2017.02.002]
[38]
Kuerten D, Johnen S, Harmening N, Souteyrand G, Walter P, Thumann G. Transplantation of PEDF-transfected pigment epithelial cells inhibits corneal neovascularization in a rabbit model. Graefes Arch Clin Exp Ophthalmol 2015; 253(7): 1061-9.
[http://dx.doi.org/10.1007/s00417-015-2954-x] [PMID: 25690979]
[39]
Mátés L, Chuah MKL, Belay E, et al. Molecular evolution of a novel hyperactive sleeping beauty transposase enables robust stable gene transfer in vertebrates. Nat Genet 2009; 41(6): 753-61.
[http://dx.doi.org/10.1038/ng.343] [PMID: 19412179]
[40]
Johnen S, Izsvák Z, Stöcker M, et al. Sleeping Beauty transposon-mediated transfection of retinal and iris pigment epithelial cells. Invest Ophthalmol Vis Sci 2012; 53(8): 4787-96.
[http://dx.doi.org/10.1167/iovs.12-9951] [PMID: 22729435]
[41]
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Δ Δ C(T)) Method. Methods 2001; 25(4): 402-8.
[http://dx.doi.org/10.1006/meth.2001.1262] [PMID: 11846609]
[42]
Kolacsek O, Krízsik V, Schamberger A, et al. Reliable transgene-independent method for determining sleeping beauty transposon copy numbers. Mob DNA 2011; 2(1): 5.
[http://dx.doi.org/10.1186/1759-8753-2-5] [PMID: 21371313]
[43]
Kaempf S, Johnen S, Salz AK, Weinberger A, Walter P, Thumann G. Effects of bevacizumab (Avastin) on retinal cells in organotypic culture. Invest Ophthalmol Vis Sci 2008; 49(7): 3164-71.
[http://dx.doi.org/10.1167/iovs.07-1265] [PMID: 18344448]
[44]
Kaempf S, Walter P, Salz AK, Thumann G. Novel organotypic culture model of adult mammalian neurosensory retina in co-culture with retinal pigment epithelium. J Neurosci Methods 2008; 173(1): 47-58.
[http://dx.doi.org/10.1016/j.jneumeth.2008.05.018] [PMID: 18632159]
[45]
Hurst J, Kuehn S, Jashari A, et al. A novel porcine ex vivo retina culture model for oxidative stress induced by H2O2. Altern Lab Anim 2017; 45(1): 11-25.
[http://dx.doi.org/10.1177/026119291704500105] [PMID: 28409994]
[46]
Geurts AM, Hackett CS, Bell JB, et al. Structure-based prediction of insertion-site preferences of transposons into chromosomes. Nucleic Acids Res 2006; 34(9): 2803-11.
[http://dx.doi.org/10.1093/nar/gkl301] [PMID: 16717285]
[47]
Kebriaei P, Izsvák Z, Narayanavari SA, Singh H, Ivics Z. Gene therapy with the sleeping beauty transposon system. Trends Genet 2017; 33(11): 852-70.
[http://dx.doi.org/10.1016/j.tig.2017.08.008] [PMID: 28964527]
[48]
Yant SR, Wu X, Huang Y, Garrison B, Burgess SM, Kay MA. High-resolution genome-wide mapping of transposon integration in mammals. Mol Cell Biol 2005; 25(6): 2085-94.
[http://dx.doi.org/10.1128/MCB.25.6.2085-2094.2005] [PMID: 15743807]
[49]
Bolhassani A, Khavari A, Oraf Z. Electroporation – In: advantages and drawbacks for delivery of drug, gene and vaccine. Application of Nanotechnology in Drug Delivery UK: Intech Open. 2014; pp. 369-98.
[http://dx.doi.org/10.5772/58376]
[50]
NIH. Available from: ClinicalTrials.gov [Accessed November 05, 2020]
[51]
Mashel TV, Tarakanchikova YV, Muslimov AR, et al. Overcoming the delivery problem for therapeutic genome editing: Current status and perspective of non-viral methods. Biomaterials 2020; 258: 120282.
[http://dx.doi.org/10.1016/j.biomaterials.2020.120282] [PMID: 32798742]
[52]
Kim JA, Cho K, Shin MS, et al. A novel electroporation method using a capillary and wire-type electrode. Biosens Bioelectron 2008; 23(9): 1353-60.
[http://dx.doi.org/10.1016/j.bios.2007.12.009] [PMID: 18242073]
[53]
Binder S, Stolba U, Krebs I, et al. Transplantation of autologous retinal pigment epithelium in eyes with foveal neovascularization resulting from age-related macular degeneration: A pilot study. Am J Ophthalmol 2002; 133(2): 215-25.
[http://dx.doi.org/10.1016/S0002-9394(01)01373-3] [PMID: 11812425]
[54]
Binder S, Krebs I, Hilgers RD, et al. Outcome of transplantation of autologous retinal pigment epithelium in age-related macular degeneration: A prospective trial. Invest Ophthalmol Vis Sci 2004; 45(11): 4151-60.
[http://dx.doi.org/10.1167/iovs.04-0118] [PMID: 15505069]
[55]
Binder S. The macula. Diagnosis, treatment and future trends. New York: Springer-VerlaglWien 2004.
[http://dx.doi.org/10.1007/978-3-7091-7985-7]
[56]
da Cruz L, Fynes K, Georgiadis O, et al. Phase 1 clinical study of an embryonic stem cell-derived retinal pigment epithelium patch in age-related macular degeneration. Nat Biotechnol 2018; 36(4): 328-37.
[http://dx.doi.org/10.1038/nbt.4114] [PMID: 29553577]
[57]
Stanga PE, Kychenthal A, Fitzke FW, et al. Retinal pigment epithelium translocation after choroidal neovascular membrane removal in age-related macular degeneration. Ophthalmology 2002; 109(8): 1492-8.
[http://dx.doi.org/10.1016/S0161-6420(02)01099-0] [PMID: 12153801]
[58]
van Zeeburg EJT, Maaijwee KJM, Missotten TOAR, Heimann H, van Meurs JC. A free retinal pigment epithelium-choroid graft in patients with exudative age-related macular degeneration: Results up to 7 years. Am J Ophthalmol 2012; 153(1): 120-7.
[http://dx.doi.org/10.1016/j.ajo.2011.06.007] [PMID: 21907969]
[59]
Chen FK, Uppal GS, MacLaren RE, et al. Long-term visual and microperimetry outcomes following autologous retinal pigment epithelium choroid graft for neovascular age-related macular degeneration. Clin Exp Ophthalmol 2009; 37(3): 275-85.
[http://dx.doi.org/10.1111/j.1442-9071.2009.01915.x] [PMID: 19459869]
[60]
Mandai M, Watanabe A, Kurimoto Y, et al. Autologous induced stem-cell-derived retinal cells for macular degeneration. N Engl J Med 2017; 376(11): 1038-46.
[http://dx.doi.org/10.1056/NEJMoa1608368] [PMID: 28296613]
[61]
Beatty S, Koh H, Phil M, Henson D, Boulton M. The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv Ophthalmol 2000; 45(2): 115-34.
[http://dx.doi.org/10.1016/S0039-6257(00)00140-5] [PMID: 11033038]
[62]
Ung L, Pattamatta U, Carnt N, Wilkinson-Berka JL, Liew G, White AJR. Oxidative stress and reactive oxygen species: A review of their role in ocular disease. Clin Sci (Lond) 2017; 131(24): 2865-83.
[http://dx.doi.org/10.1042/CS20171246] [PMID: 29203723]
[63]
Cao W, Tombran-Tink J, Chen W, Mrazek D, Elias R, McGinnis JF. Pigment epithelium-derived factor protects cultured retinal neurons against hydrogen peroxide-induced cell death. J Neurosci Res 1999; 57(6): 789-800.
[http://dx.doi.org/10.1002/(SICI)1097-4547(19990915)57:6<789::AID-JNR4>3.0.CO;2-M] [PMID: 10467250]
[64]
Pang IH, Zeng H, Fleenor DL, Clark AF. Pigment epithelium-derived factor protects retinal ganglion cells. BMC Neurosci 2007; 8: 11.
[http://dx.doi.org/10.1186/1471-2202-8-11] [PMID: 17261189]
[65]
Wang X, Liu X, Ren Y, et al. PEDF protects human retinal pigment epithelial cells against oxidative stress via upregulation of UCP2 expression. Mol Med Rep 2019; 19(1): 59-74.
[PMID: 30431098]
[66]
Brook N, Brook E, Dharmarajan A, Chan A, Dass CR. The role of pigment epithelium-derived factor in protecting against cellular stress. Free Radic Res 2019; 53(11-12): 1166-80.
[http://dx.doi.org/10.1080/10715762.2019.1697809] [PMID: 31760841]
[67]
Choi JK, Choi BH, Ha Y, et al. Signal transduction pathways of GM-CSF in neural cell lines. Neurosci Lett 2007; 420(3): 217-22.
[http://dx.doi.org/10.1016/j.neulet.2007.03.065] [PMID: 17556097]
[68]
Chao J-R, Wang J-M, Lee S-F, et al. mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling pathway and is one component of the GM-CSF viability response. Mol Cell Biol 1998; 18(8): 4883-98.
[http://dx.doi.org/10.1128/MCB.18.8.4883] [PMID: 9671497]
[69]
Geiger RC, Waters CM, Kamp DW, Glucksberg MR. KGF prevents oxygen-mediated damage in ARPE-19 cells. Invest Ophthalmol Vis Sci 2005; 46(9): 3435-42.
[http://dx.doi.org/10.1167/iovs.04-1487] [PMID: 16123449]
[70]
Zhuge CC, Xu JY, Zhang J, et al. Fullerenol protects retinal pigment epithelial cells from oxidative stress-induced premature senescence via activating SIRT1. Invest Ophthalmol Vis Sci 2014; 55(7): 4628-38.
[http://dx.doi.org/10.1167/iovs.13-13732] [PMID: 24845634]
[71]
Tu G, Zhang YF, Wei W, et al. Allicin attenuates H2O2-induced cytotoxicity in retinal pigmented epithelial cells by regulating the levels of reactive oxygen species. Mol Med Rep 2016; 13(3): 2320-6.
[http://dx.doi.org/10.3892/mmr.2016.4797] [PMID: 26781848]
[72]
Hao Yiming, Liu Jie, Ziyuan Wang LY. Piceatannol protects human retinal pigment epithelial cells against hydrogen peroxide induced oxidative stress and apoptosis through modulating P13K/Akt signaling pathway. Nutrients 2019; 11: 1-13.
[http://dx.doi.org/10.3390/nu11071515]
[73]
Pérez-León J, Frech MJ, Schröder JE, et al. Spontaneous synaptic activity in an organotypic culture of the mouse retina. Invest Ophthalmol Vis Sci 2003; 44(3): 1376-87.
[http://dx.doi.org/10.1167/iovs.02-0702] [PMID: 12601071]
[74]
Krasnov MS, Grigorian EN, Iamskova VP. An organotypic culture of the newt retina together with other tissues of the posterior eye segment as a model for studying the effects of the cell adhesion glycoproteins. Izv Akad Nauk Ser Biol 2003; 30(1): 22-36.
[PMID: 12647537]
[75]
Li Y, Zhang Y, Qi S, Su G. Retinal organotypic culture - a candidate for research on retinas. Tissue Cell 2018; 51: 1-7.
[http://dx.doi.org/10.1016/j.tice.2018.01.005] [PMID: 29622082]
[76]
Hernández-Pinto A, Polato F, Subramanian P, et al. PEDF peptides promote photoreceptor survival in rd10 retina models. Exp Eye Res 2019; 184: 24-9.
[http://dx.doi.org/10.1016/j.exer.2019.04.008] [PMID: 30980815]
[77]
Chen Y, Yang J, Geng H, et al. Photoreceptor degeneration in microphthalmia (Mitf) mice: Partial rescue by pigment epithelium-derived factor. Dis Model Mech 2019; 12(1): 1-9.
[http://dx.doi.org/10.1242/dmm.035642] [PMID: 30651300]
[78]
Gorrini C, Harris IS, Mak TW. Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 2013; 12(12): 931-47.
[http://dx.doi.org/10.1038/nrd4002] [PMID: 24287781]
[79]
Donadelli M, Dando I, Fiorini C, Palmieri M. UCP2, a mitochondrial protein regulated at multiple levels. Cell Mol Life Sci 2014; 71(7): 1171-90.
[http://dx.doi.org/10.1007/s00018-013-1407-0] [PMID: 23807210]
[80]
Kropp M, Tobalem S, Kecik M, et al. Improved transferability of a disease model for avascular age-related macular degeneration (AMD) to evaluate cell-based gene therapies using aged mice. ISSCR Annual meeting. Boston, USA. 2020. Meeting Abstract: MDD228. Poster

Rights & Permissions Print Cite
Article Metrics
23
1
© 2025 Bentham Science Publishers | Privacy Policy