综述
ENGLISH ABSTRACT
外泌体在青光眼诊疗中的作用研究进展
酆欣婷
张旭 [综述]
作者及单位信息
·
DOI: 10.3760/cma.j.cn115989-20220429-00186
Advances in the study of exosomes in glaucoma diagnosis and treatment
Feng Xinting
Zhang Xu
Authors Info & Affiliations
Feng Xinting
Affiliated Eye Hospital of Nanchang University, Nanchang University School of Ophthalmology & Optometry, Nanchang 330006, China
Zhang Xu
Affiliated Eye Hospital of Nanchang University, Nanchang University School of Ophthalmology & Optometry, Nanchang 330006, China
·
DOI: 10.3760/cma.j.cn115989-20220429-00186
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摘要

外泌体是由各种细胞分泌产生,广泛存在于生物体液中的纳米级脂质双分子层结构小囊泡,其内容物复杂,具有多种生物学功能。外泌体在青光眼的发生和发展中扮演重要作用,眼内外泌体通过运输青光眼相关蛋白、调节Wnt信号通路、影响细胞外基质周转等参与小梁网细胞调节,从而影响房水循环;小胶质细胞外泌体介导视网膜神经炎症和相关的炎症信号通路。此外,眼内液中外泌体稳定存在,其中差异性表达的蛋白质、RNA等内容物使外泌体具有作为青光眼生物标志物的潜力。在青光眼治疗方面,干细胞源性外泌体抑制胶质细胞活化及神经炎症,减少视网膜神经节细胞的损失,起到神经保护作用。外泌体可通过血-视网膜屏障,输送神经营养因子、药物或其他治疗分子到靶细胞中,调节靶细胞的功能,为青光眼视神经退行性病变提供了新的治疗手段。本文总结国内外青光眼与外泌体领域的研究进展,并对外泌体在青光眼的发生和发展、诊断及治疗中的作用及机制进行综述,以期为早期诊断和治疗青光眼提供新思路。

外泌体;青光眼;干细胞;细胞通讯;神经保护
ABSTRACT

Exosomes are small vesicles with nanoscale lipid bilayer structures, which are secreted by various cells and are widely present in biological fluids, with complex contents and multiple biological functions.Exosomes play an important role in the development of glaucoma.Exosomes in the eye are involved in trabecular meshwork cell regulation by transporting glaucoma-associated proteins, regulating the Wnt signaling pathway, and affecting extracellular matrix turnover, thereby affecting the atrial circulation.Microglial exosomes mediate retinal neuroinflammation and related inflammatory signaling pathways.In addition, the stable presence of exosomes in intraocular fluid, in which differentially expressed proteins, RNA and other contents give exosomes potential as glaucoma biomarkers.In the treatment of glaucoma, stem cell-derived exosomes inhibit glial cell activation and neuroinflammation, reduce the loss of retinal ganglion cells, and act as neuroprotective agents.Exosomes can cross the blood-retinal barrier, deliver neurotrophic factors, drugs or other therapeutic molecules to target cells, regulate the function of target cells, and provide a new therapeutic tool for glaucomatous optic nerve degeneration.This paper summarized the research progress in the field of glaucoma and exosomes at home and abroad, and reviewed the role of exosomes and related mechanisms in the development, diagnosis, and treatment of glaucoma, expecting to provide new ideas for the early diagnosis and treatment of glaucoma.

Exosomes;Glaucoma;Stem cells;Cell communication;Neuroprotection
Zhang Xu, Email: mocdef.3ab6191gnahzux
引用本文

酆欣婷,张旭. 外泌体在青光眼诊疗中的作用研究进展[J]. 中华实验眼科杂志,2023,41(02):173-177.

DOI:10.3760/cma.j.cn115989-20220429-00186

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外泌体是目前发现最小的一种细胞外囊泡,广泛分布于人体血液、唾液、脑脊液、尿液等各种体液中 [ 1 ]。由于外泌体在人生理状态和疾病中的重要作用,以及在疾病诊疗中潜在的临床应用价值,近年来对其研究越来越多。青光眼是全球首位不可逆性致盲眼病,其特征是视网膜神经节细胞(retinal ganglion cells,RGCs)及其轴突进行性丧失,并伴随视野缺损 [ 2 ]。原发性青光眼早期症状隐匿,不易被发现,在我国一半以上的患者被诊断为青光眼时即有严重视野缺损 [ 3 ],错失了最佳治疗时机,这提示早期诊断对于降低视力损害的风险至关重要。研究表明,外泌体是参与青光眼发病及进展的重要介质,同时可能作为青光眼早期诊断的潜在标志物及治疗载体。此类纳米级细胞外囊泡可以穿过生物屏障,直接靶向目标受体细胞,递送治疗分子,可能为青光眼视神经退行性病变的治疗提供新思路。本文就外泌体在青光眼发生和诊疗中的研究进展进行综述。
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参考文献
[1]
Liu J Jiang F Jiang Y et al. Roles of exosomes in ocular diseases[J/OL]Int J Nanomedicine 2020151051910538[2022-07-10]https://pubmed.ncbi.nlm.nih.gov/33402823/. DOI: 10.2147/IJN.S277190 .
返回引文位置Google Scholar
百度学术
万方数据
[2]
Weinreb RN Aung T Medeiros FA . The pathophysiology and treatment of glaucoma:a review[J]JAMA 2014311(18)∶19011911. DOI: 10.1001/jama.2014.3192 .
返回引文位置Google Scholar
百度学术
万方数据
[3]
Liang Y Jiang J Ou W et al. Effect of community screening on the demographic makeup and clinical severity of glaucoma patients receiving care in urban China[J]Am J Ophthalmol 201819517. DOI: 10.1016/j.ajo.2018.07.013 .
返回引文位置Google Scholar
百度学术
万方数据
[4]
Kalluri R LeBleu VS . The biology,function,and biomedical applications of exosomes[J/OL]Science 2020367(6478)∶eaau6977[2022-07-10]https://pubmed.ncbi.nlm.nih.gov/32029601/. DOI: 10.1126/science.aau6977 .
返回引文位置Google Scholar
百度学术
万方数据
[5]
Villarroya-Beltri C Baixauli F Gutiérrez-Vázquez C et al. Sorting it out:regulation of exosome loading[J]Semin Cancer Biol 201428313. DOI: 10.1016/j.semcancer.2014.04.009 .
返回引文位置Google Scholar
百度学术
万方数据
[6]
Gurung S Perocheau D Touramanidou L et al. The exosome journey:from biogenesis to uptake and intracellular signalling[J/OL]Cell Commun Signal 202119(1)∶47[2022-07-11]https://pubmed.ncbi.nlm.nih.gov/33892745/. DOI: 10.1186/s12964-021-00730-1 .
返回引文位置Google Scholar
百度学术
万方数据
[7]
Wei H Chen Q Lin L et al. Regulation of exosome production and cargo sorting[J]Int J Biol Sci 202117(1)∶163177. DOI: 10.7150/ijbs.53671 .
返回引文位置Google Scholar
百度学术
万方数据
[8]
Noonin C Thongboonkerd V Exosome-inflammasome crosstalk and their roles in inflammatory responses[J]Theranostics 202111(9)∶44364451. DOI: 10.7150/thno.54004 .
返回引文位置Google Scholar
百度学术
万方数据
[9]
Li Q Wang H Peng H et al. Exosomes:versatile nano mediators of immune regulation[J/OL]Cancers (Basel) 201911(10)∶1557[2022-07-11]https://pubmed.ncbi.nlm.nih.gov/31615107/. DOI: 10.3390/cancers11101557 .
返回引文位置Google Scholar
百度学术
万方数据
[10]
Zhang Y Chopp M Liu XS et al. Exosomes derived from mesenchymal stromal cells promote axonal growth of cortical neurons[J]Mol Neurobiol 201754(4)∶26592673. DOI: 10.1007/s12035-016-9851-0 .
返回引文位置Google Scholar
百度学术
万方数据
[11]
Hassanpour M Rezabakhsh A Rezaie J et al. Exosomal cargos modulate autophagy in recipient cells via different signaling pathways[J/OL]Cell Biosci 20201092[2022-07-12]https://pubmed.ncbi.nlm.nih.gov/32765827/. DOI: 10.1186/s13578-020-00455-7 .
返回引文位置Google Scholar
百度学术
万方数据
[12]
Rong Y Liu W Wang J et al. Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy[J/OL]Cell Death Dis 201910(5)∶340[2022-07-12]https://pubmed.ncbi.nlm.nih.gov/31000697/. DOI: 10.1038/s41419-019-1571-8 .
返回引文位置Google Scholar
百度学术
万方数据
[13]
Klingeborn M Dismuke WM Bowes Rickman C et al. Roles of exosomes in the normal and diseased eye[J]Prog Retin Eye Res 201759158177. DOI: 10.1016/j.preteyeres.2017.04.004 .
返回引文位置Google Scholar
百度学术
万方数据
[14]
廖志雄楼正青肖中兔房水来源exosomes的分离与鉴定及其免疫抑制功能的研究[J]浙江大学学报(医学版) 201241(3)∶315319. DOI: 10.3785/j.issn.1008-9292.2012.03.014 .
返回引文位置Google Scholar
百度学术
万方数据
Liao ZX Lou ZQ Xiao Z Isolation of rabbit aqueous humor-derived exosomes and their immunosuppression function[J]J Zhejiang Univ (Medical Sciences) 201241(3)∶315319. DOI: 10.3785/j.issn.1008-9292.2012.03.014 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[15]
Knickelbein JE Liu B Arakelyan A et al. Modulation of immune responses by extracellular vesicles from retinal pigment epithelium[J]Invest Ophthalmol Vis Sci 201657(10)∶41014107. DOI: 10.1167/iovs.15-18353 .
返回引文位置Google Scholar
百度学术
万方数据
[16]
Vidal-Sanz M Salinas-Navarro M Nadal-Nicolás FM et al. Understanding glaucomatous damage:anatomical and functional data from ocular hypertensive rodent retinas[J]Prog Retin Eye Res 201231(1)∶127. DOI: 10.1016/j.preteyeres.2011.08.001 .
返回引文位置Google Scholar
百度学术
万方数据
[17]
Lerner N Schreiber-Avissar S Beit-Yannai E Extracellular vesicle-mediated crosstalk between NPCE cells and TM cells result in modulation of Wnt signalling pathway and ECM remodelling[J]J Cell Mol Med 202024(8)∶46464658. DOI: 10.1111/jcmm.15129 .
返回引文位置Google Scholar
百度学术
万方数据
[18]
Borrás T The effects of myocilin expression on functionally relevant trabecular meshwork genes:a mini-review[J]J Ocul Pharmacol Ther 201430(2-3)∶202212. DOI: 10.1089/jop.2013.0218 .
返回引文位置Google Scholar
百度学术
万方数据
[19]
Stamer WD Hoffman EA Luther JM et al. Protein profile of exosomes from trabecular meshwork cells[J]J Proteomics 201174(6)∶796804. DOI: 10.1016/j.jprot.2011.02.024 .
返回引文位置Google Scholar
百度学术
万方数据
[20]
Tabak S Schreiber-Avissar S Beit-Yannai E Extracellular vesicles have variable dose-dependent effects on cultured draining cells in the eye[J]J Cell Mol Med 201822(3)∶19922000. DOI: 10.1111/jcmm.13505 .
返回引文位置Google Scholar
百度学术
万方数据
[21]
Dismuke WM Klingeborn M Stamer WD . Mechanism of fibronectin binding to human trabecular meshwork exosomes and its modulation by dexamethasone[J/OL]PLoS One 201611(10)∶e0165326[2022-07-13]https://pubmed.ncbi.nlm.nih.gov/27783649/. DOI: 10.1371/journal.pone.0165326 .
返回引文位置Google Scholar
百度学术
万方数据
[22]
Madeira MH Boia R Santos PF et al. Contribution of microglia-mediated neuroinflammation to retinal degenerative diseases[J/OL]Mediators Inflamm 20152015673090[2022-07-14]https://pubmed.ncbi.nlm.nih.gov/25873768/. DOI: 10.1155/2015/673090 .
返回引文位置Google Scholar
百度学术
万方数据
[23]
Aires ID Ribeiro-Rodrigues T Boia R et al. Exosomes derived from microglia exposed to elevated pressure amplify the neuroinflammatory response in retinal cells[J]Glia 202068(12)∶27052724. DOI: 10.1002/glia.23880 .
返回引文位置Google Scholar
百度学术
万方数据
[24]
Paolicelli RC Bergamini G Rajendran L Cell-to-cell communication by extracellular vesicles:focus on microglia[J]Neuroscience 2019405148157. DOI: 10.1016/j.neuroscience.2018.04.003 .
返回引文位置Google Scholar
百度学术
万方数据
[25]
Ramirez AI de Hoz R Salobrar-Garcia E et al. The role of microglia in retinal neurodegeneration:Alzheimer's disease,Parkinson,and glaucoma[J/OL]Front Aging Neurosci 20179214[2022-07-14]https://pubmed.ncbi.nlm.nih.gov/28729832/. DOI: 10.3389/fnagi.2017.00214 .
返回引文位置Google Scholar
百度学术
万方数据
[26]
Asai H Ikezu S Tsunoda S et al. Depletion of microglia and inhibition of exosome synthesis halt tau propagation[J]Nat Neurosci 201518(11)∶15841593. DOI: 10.1038/nn.4132 .
返回引文位置Google Scholar
百度学术
万方数据
[27]
González E Falcón-Pérez JM . Cell-derived extracellular vesicles as a platform to identify low-invasive disease biomarkers[J]Expert Rev Mol Diagn 201515(7)∶907923. DOI: 10.1586/14737159.2015.1043272 .
返回引文位置Google Scholar
百度学术
万方数据
[28]
Ohno Y Yako T Satoh K et al. Retinal damage alters gene expression profile in lacrimal glands of mice[J]J Pharmacol Sci 2022149(1)∶2026. DOI: 10.1016/j.jphs.2022.02.007 .
返回引文位置Google Scholar
百度学术
万方数据
[29]
Rossi C Cicalini I Cufaro MC et al. Multi-omics approach for studying tears in treatment-naïve glaucoma patients[J/OL]Int J Mol Sci 201920(16)∶4029[2022-07-15]https://pubmed.ncbi.nlm.nih.gov/31426571/. DOI: 10.3390/ijms20164029 .
返回引文位置Google Scholar
百度学术
万方数据
[30]
Hsu MY Chiu CC Wang JY et al. Paper-based microfluidic platforms for understanding the role of exosomes in the pathogenesis of major blindness-threatening diseases[J/OL]Nanomaterials (Basel) 20188(5)∶310[2022-07-15]https://pubmed.ncbi.nlm.nih.gov/29738436/. DOI: 10.3390/nano8050310 .
返回引文位置Google Scholar
百度学术
万方数据
[31]
Dismuke WM Challa P Navarro I et al. Human aqueous humor exosomes[J]Exp Eye Res 20151327377. DOI: 10.1016/j.exer.2015.01.019 .
返回引文位置Google Scholar
百度学术
万方数据
[32]
Saccà SC Centofanti M Izzotti A New proteins as vascular biomarkers in primary open angle glaucomatous aqueous humor[J]Invest Ophthalmol Vis Sci 201253(7)∶42424253. DOI: 10.1167/iovs.11-8902 .
返回引文位置Google Scholar
百度学术
万方数据
[33]
Lauwers E Wang YC Gallardo R et al. Hsp90 mediates membrane deformation and exosome release[J]Mol Cell 201871(5)∶689702. DOI: 10.1016/j.molcel.2018.07.016 .
返回引文位置Google Scholar
百度学术
万方数据
[34]
Mirzaei M Gupta VB Chick JM et al. Age-related neurodegenerative disease associated pathways identified in retinal and vitreous proteome from human glaucoma eyes[J/OL]Sci Rep 20177(1)∶12685[2022-07-15]https://pubmed.ncbi.nlm.nih.gov/28978942/. DOI: 10.1038/s41598-017-12858-7 .
返回引文位置Google Scholar
百度学术
万方数据
[35]
Zhao Y Weber SR Lease J et al. Liquid biopsy of vitreous reveals an abundant vesicle population consistent with the size and morphology of exosomes[J/OL]Transl Vis Sci Technol 20187(3)∶6[2022-07-16]https://pubmed.ncbi.nlm.nih.gov/29774170/. DOI: 10.1167/tvst.7.3.6 .
返回引文位置Google Scholar
百度学术
万方数据
[36]
池在龙张文梦关吉田血浆/血清外泌体miRNA作为青光眼诊断标志物中的应用:CN201910094763.X[P]. 2019-04-16.
返回引文位置Google Scholar
百度学术
万方数据
[37]
池在龙张文梦lncRNA TRAM2作为青光眼诊断标志物中的应用:CN201910640208.2[P]. 2019-10-29.
返回引文位置Google Scholar
百度学术
万方数据
[38]
Mead B Tomarev S Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through miRNA-dependent mechanisms[J]Stem Cells Transl Med 20176(4)∶12731285. DOI: 10.1002/sctm.16-0428 .
返回引文位置Google Scholar
百度学术
万方数据
[39]
Liu S Fan M Xu JX et al. Exosomes derived from bone-marrow mesenchymal stem cells alleviate cognitive decline in AD-like mice by improving BDNF-related neuropathology[J/OL]J Neuroinflammation 202219(1)∶35[2022-07-17]https://pubmed.ncbi.nlm.nih.gov/35130907/. DOI: 10.1186/s12974-022-02393-2 .
返回引文位置Google Scholar
百度学术
万方数据
[40]
Balbi C Piccoli M Barile L et al. First characterization of human amniotic fluid stem cell extracellular vesicles as a powerful paracrine tool endowed with regenerative potential[J]Stem Cells Transl Med 20176(5)∶13401355. DOI: 10.1002/sctm.16-0297 .
返回引文位置Google Scholar
百度学术
万方数据
[41]
Mead B Chamling X Zack DJ et al. TNFα-mediated priming of mesenchymal stem cells enhances their neuroprotective effect on retinal ganglion cells[J/OL]Invest Ophthalmol Vis Sci 202061(2)∶6[2022-07-18]https://pubmed.ncbi.nlm.nih.gov/32031578/. DOI: 10.1167/iovs.61.2.6
返回引文位置Google Scholar
百度学术
万方数据
[42]
Mathew B Ravindran S Liu X et al. Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion[J]Biomaterials 2019197146160. DOI: 10.1016/j.biomaterials.2019.01.016 .
返回引文位置Google Scholar
百度学术
万方数据
[43]
Mead B Ahmed Z Tomarev S Mesenchymal stem cell-derived small extracellular vesicles promote neuroprotection in a genetic DBA/2J mouse model of glaucoma[J]Invest Ophthalmol Vis Sci 201859(13)∶54735480. DOI: 10.1167/iovs.18-25310 .
返回引文位置Google Scholar
百度学术
万方数据
[44]
Mead B Amaral J Tomarev S Mesenchymal stem cell-derived small extracellular vesicles promote neuroprotection in rodent models of glaucoma[J]Invest Ophthalmol Vis Sci 201859(2)∶702714. DOI: 10.1167/iovs.17-22855 .
返回引文位置Google Scholar
百度学术
万方数据
[45]
Pan D Chang X Xu M et al. UMSC-derived exosomes promote retinal ganglion cells survival in a rat model of optic nerve crush[J]J Chem Neuroanat 201996134139. DOI: 10.1016/j.jchemneu.2019.01.006 .
返回引文位置Google Scholar
百度学术
万方数据
[46]
Seyedrazizadeh SZ Poosti S Nazari A et al. Extracellular vesicles derived from human ES-MSCs protect retinal ganglion cells and preserve retinal function in a rodent model of optic nerve injury[J/OL]Stem Cell Res Ther 202011(1)∶203[2022-07-19]https://pubmed.ncbi.nlm.nih.gov/32460894/. DOI: 10.1186/s13287-020-01702-x .
返回引文位置Google Scholar
百度学术
万方数据
[47]
Sun D Zhuang X Xiang X et al. A novel nanoparticle drug delivery system:the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes[J]Mol Ther 201018(9)∶16061614. DOI: 10.1038/mt.2010.105 .
返回引文位置Google Scholar
百度学术
万方数据
[48]
林浩王颖间充质干细胞来源外泌体靶向修饰在眼病治疗中的应用前景[J]中华实验眼科杂志 202038(10)∶890894. DOI: 10.3760/cma.j.cn115989-20200319-00186 .
返回引文位置Google Scholar
百度学术
万方数据
Lin H Wang Y Modification of mesenchymal stem cell derived exosomes and its application prospects in the treatment of eye disease[J]Chin J Exp Ophthalmol 202038(10)∶890894. DOI: 10.3760/cma.j.cn115989-20200319-00186 .
Goto CitationGoogle Scholar
Baidu Scholar
Wanfang Data
[49]
Zhang X Zhang H Gu J et al. Engineered extracellular vesicles for cancer therapy[J/OL]Adv Mater 202133(14)∶e2005709[2022-07-20]https://pubmed.ncbi.nlm.nih.gov/33644908/. DOI: 10.1002/adma.202005709 .
返回引文位置Google Scholar
百度学术
万方数据
[50]
Théry C Witwer KW Aikawa E et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018)∶a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines[J/OL]J Extracell Vesicles 20187(1)∶1535750[2022-07-20]https://pubmed.ncbi.nlm.nih.gov/30637094/. DOI: 10.1080/20013078.2018.1535750 .
返回引文位置Google Scholar
百度学术
万方数据
[51]
Mathew B Torres LA Gamboa Acha L et al. Uptake and distribution of administered bone marrow mesenchymal stem cell extracellular vesicles in retina[J/OL]Cells 202110(4)∶730[2022-07-21]https://pubmed.ncbi.nlm.nih.gov/33806128/. DOI: 10.3390/cells10040730 .
返回引文位置Google Scholar
百度学术
万方数据
备注信息
A
张旭,Email: mocdef.3ab6191gnahzux
B
所有作者均声明不存在利益冲突
C
感谢南昌大学眼视光学院彭振对本文的指导
D
国家自然科学基金项目 (81860170)
江西省自然科学基金项目 (20181ACG70010)
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