1,019
Views
36
CrossRef citations to date
0
Altmetric
Review

Roles of Exosomes in Ocular Diseases

, , , , , , , & show all
Pages 10519-10538 | Published online: 29 Dec 2020

References

  • Mathieu M, Martin-Jaular L, Lavieu G, Thery C. Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nat Cell Biol. 2019;21(1):9–17. doi:10.1038/s41556-018-0250-930602770
  • Hessvik NP, Llorente A. Current knowledge on exosome biogenesis and release. Cell Mol Life Sci. 2018;75(2):193–208. doi:10.1007/s00018-017-2595-928733901
  • Pan BT, Johnstone RM. Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell. 1983;33(3):967–978. doi:10.1016/0092-8674(83)90040-56307529
  • Pan BT, Teng K, Wu C, Adam M, Johnstone RM. Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J Cell Biol. 1985;101(3):942–948. doi:10.1083/jcb.101.3.9422993317
  • Johnstone RM, Adam M, Hammond JR, Orr L, Turbide C. Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J Biol Chem. 1987;262(19):9412–9420.3597417
  • Yu B, Zhang X, Li X. Exosomes derived from mesenchymal stem cells. Int J Mol Sci. 2014;15(3):4142–4157. doi:10.3390/ijms1503414224608926
  • Mueller SK, Nocera AL, Bleier BS. Exosome function in aerodigestive mucosa. Nanomedicine. 2018;14(2):269–277. doi:10.1016/j.nano.2017.10.00829127037
  • Colombo M, Raposo G, Thery C. Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol. 2014;30:255–289. doi:10.1146/annurev-cellbio-101512-12232625288114
  • Li S, Li Y, Chen B, et al. exoRBase: a database of circRNA, lncRNA and mRNA in human blood exosomes. Nucleic Acids Res. 2018;46(D1):D106–D112. doi:10.1093/nar/gkx89130053265
  • Klingeborn M, Dismuke WM, Bowes Rickman C, Stamer WD. Roles of exosomes in the normal and diseased eye. Prog Retin Eye Res. 2017;59:158–177. doi:10.1016/j.preteyeres.2017.04.00428465248
  • Kang X, Zuo Z, Hong W, Tang H, Geng W. Progress of research on exosomes in the protection against ischemic brain injury. Front Neurosci. 2019;13:1149. doi:10.3389/fnins.2019.0114931736691
  • Yamashita T, Takahashi Y, Takakura Y. Possibility of exosome-based therapeutics and challenges in production of exosomes eligible for therapeutic application. Biol Pharm Bull. 2018;41(6):835–842. doi:10.1248/bpb.b18-0013329863072
  • Akbari A, Jabbari N, Sharifi R, et al. Free and hydrogel encapsulated exosome-based therapies in regenerative medicine. Life Sci. 2020. doi:10.1016/j.lfs.2020.117447
  • Zhang L, Liu H, Jia L, et al. Exosomes mediate hippocampal and cortical neuronal injury induced by hepatic ischemia-reperfusion injury through activating pyroptosis in rats. Oxid Med Cell Longev. 2019;2019:1–17. doi:10.1155/2019/3753485
  • Li N, Zhao L, Wei Y, Ea VL, Nian H, Wei R. Recent advances of exosomes in immune-mediated eye diseases. Stem Cell Res Ther. 2019;10(1):278. doi:10.1186/s13287-019-1372-031470892
  • Tkach M, Thery C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164(6):1226–1232. doi:10.1016/j.cell.2016.01.04326967288
  • Edgar JR. Q&A: what are exosomes, exactly? BMC Biol. 2016;14:46. doi:10.1186/s12915-016-0268-z27296830
  • Mulcahy LA, Pink RC, Carter DR. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles. 2014;3doi 10.3402/jev.v3.24641.
  • McKelvey KJ, Powell KL, Ashton AW, Morris JM, McCracken SA. Exosomes: mechanisms of uptake. J Circ Biomark. 2015;4:7. doi:10.5772/6118628936243
  • Nedaeinia R, Manian M, Jazayeri M, et al. Circulating exosomes and exosomal microRNAs as biomarkers in gastrointestinal cancer. Cancer Gene Ther. 2017;24(2):48–56. doi:10.1038/cgt.2016.7727982021
  • Cho S, Yang H, Rhee W. Simultaneous multiplexed detection of exosomal microRNAs and surface proteins for prostate cancer diagnosis. Biosens Bioelectron. 2019;146:111749. doi:10.1016/j.bios.2019.11174931600625
  • Xia X, Wang Y, Huang Y, Zhang H, Lu H, Zheng JC. Exosomal miRNAs in central nervous system diseases: biomarkers, pathological mediators, protective factors and therapeutic agents. Prog Neurobiol. 2019;183:101694. doi:10.1016/j.pneurobio.2019.10169431542363
  • Betzer O, Perets N, Angel A, et al. In vivo neuroimaging of exosomes using gold nanoparticles. ACS Nano. 2017;11(11):10883–10893. doi:10.1021/acsnano.7b0449528960957
  • Haney MJ, Klyachko NL, Zhao Y, et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release. 2015;207:18–30. doi:10.1016/j.jconrel.2015.03.03325836593
  • Ha D, Yang N, Nadithe V. Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm Sin B. 2016;6(4):287–296. doi:10.1016/j.apsb.2016.02.00127471669
  • Kibria G, Ramos EK, Wan Y, Gius DR, Liu H. Exosomes as a drug delivery system in cancer therapy: potential and challenges. Mol Pharm. 2018;15(9):3625–3633. doi:10.1021/acs.molpharmaceut.8b0027729771531
  • Bourne RRA, Jonas JB, Bron AM, et al. Prevalence and causes of vision loss in high-income countries and in Eastern and Central Europe in 2015: magnitude, temporal trends and projections. Br J Ophthalmol. 2018;102(5):575–585. doi:10.1136/bjophthalmol-2017-31125829545417
  • Sabanayagam C, Cheng C-Y. Global causes of vision loss in 2015: are we on track to achieve the Vision 2020 target? The Lancet Global Health. 2017;5(12):e1164–e1165. doi:10.1016/s2214-109x(17)30412-629032196
  • Flaxman SR, Bourne RRA, Resnikoff S, et al. Global causes of blindness and distance vision impairment 1990–2020: a systematic review and meta-analysis. The Lancet Global Health. 2017;5(12):e1221–e1234. doi:10.1016/S2214-109X(17)30393-529032195
  • Fricke TR, Tahhan N, Resnikoff S, et al. Global prevalence of presbyopia and vision impairment from uncorrected presbyopia: systematic review, meta-analysis, and modelling. Ophthalmology. 2018;125(10):1492–1499. doi:10.1016/j.ophtha.2018.04.01329753495
  • DelMonte D, Kim T. Anatomy and physiology of the cornea. J Cataract Refract Surg. 2011;37(3):588–598. doi:10.1016/j.jcrs.2010.12.03721333881
  • Vallabh NA, Romano V, Willoughby CE. Mitochondrial dysfunction and oxidative stress in corneal disease. Mitochondrion. 2017;36:103–113. doi:10.1016/j.mito.2017.05.00928549842
  • Forrester JV, Kuffova L, Dick AD. Autoimmunity, autoinflammation, and infection in uveitis. Am J Ophthalmol. 2018;189:77–85. doi:10.1016/j.ajo.2018.02.01929505775
  • Mathew B, Ravindran S, Liu X, et al. Mesenchymal stem cell-derived extracellular vesicles and retinal ischemia-reperfusion. Biomaterials. 2019;197:146–160. doi:10.1016/j.biomaterials.2019.01.01630654160
  • Yu B, Li XR, Zhang XM. Mesenchymal stem cell-derived extracellular vesicles as a new therapeutic strategy for ocular diseases. World J Stem Cells. 2020;12(3):178–187. doi:10.4252/wjsc.v12.i3.17832266050
  • Mead B, Tomarev S. Extracellular vesicle therapy for retinal diseases. Prog Retin Eye Res. 2020;79:100849. doi:10.1016/j.preteyeres.2020.10084932169632
  • Li SF, Han Y, Wang F, Su Y. Progress in exosomes and their potential use in ocular diseases. Int J Ophthalmol. 2020;13(9):1493–1498. doi:10.18240/ijo.2020.09.2332953591
  • Villarroya-Beltri C, Baixauli F, Gutierrez-Vazquez C, Sanchez-Madrid F, Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin Cancer Biol. 2014;28:3–13. doi:10.1016/j.semcancer.2014.04.00924769058
  • Chen L, Chen R, Kemper S, Brigstock DR. Pathways of production and delivery of hepatocyte exosomes. J Cell Commun Signal. 2018;12(1):343–357. doi:10.1007/s12079-017-0421-729063370
  • Gurunathan S, Kang MH, Jeyaraj M, Qasim M, Kim JH. Review of the isolation, characterization, biological function, and multifarious therapeutic approaches of exosomes. Cells. 2019;8(4):Apr. doi:10.3390/cells8040307
  • Alenquer M, Amorim MJ. Exosome biogenesis, regulation, and function in viral infection. Viruses. 2015;7(9):5066–5083. doi:10.3390/v709286226393640
  • Colombo M, Moita C, van Niel G, et al. Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci. 2013;126(Pt 24):5553–5565. doi:10.1242/jcs.12886824105262
  • Juan T, Fürthauer M. Biogenesis and function of ESCRT-dependent extracellular vesicles. Semin Cell Dev Biol. 2018;74:66–77. doi:10.1016/j.semcdb.2017.08.02228807885
  • Baietti MF, Zhang Z, Mortier E, et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol. 2012;14(7):677–685. doi:10.1038/ncb250222660413
  • Hikita T, Kuwahara A, Watanabe R, Miyata M, Oneyama C. Src in endosomal membranes promotes exosome secretion and tumor progression. Sci Rep. 2019;9(1):3265. doi:10.1038/s41598-019-39882-z30824759
  • Hyenne V, Labouesse M, Goetz JG. The Small GTPase Ral orchestrates MVB biogenesis and exosome secretion. Small GTPases. 2018;9(6):445–451. doi:10.1080/21541248.2016.125137827875100
  • Murrow L, Debnath J. Atg12-Atg3 coordinates basal autophagy, endolysosomal trafficking, and exosome release. Mol Cell Oncol. 2018;5(5):e1039191. doi:10.1080/23723556.2015.103919130263931
  • Yoon S, Kovalenko A, Bogdanov K, Wallach D. MLKL, the protein that mediates necroptosis, also regulates endosomal trafficking and extracellular vesicle generation. Immunity. 2017;47(1):51–65 e7. doi:10.1016/j.immuni.2017.06.00128666573
  • Zhang J, Li S, Li L, et al. Exosome and exosomal microRNA: trafficking, sorting, and function. Genomics Proteomics Bioinformatics. 2015;13(1):17–24. doi:10.1016/j.gpb.2015.02.00125724326
  • Skotland T, Sandvig K, Llorente A. Lipids in exosomes: current knowledge and the way forward. Prog Lipid Res. 2017;66:30–41. doi:10.1016/j.plipres.2017.03.00128342835
  • Pegtel DM, Gould SJ. Exosomes. Annu Rev Biochem. 2019;88:487–514. doi:10.1146/annurev-biochem-013118-11190231220978
  • Yim N, Ryu S-W, Choi K, et al. Exosome engineering for efficient intracellular delivery of soluble proteins using optically reversible protein–protein interaction module. Nat Commun. 2016;7. doi:10.1038/ncomms12277
  • He C, Zheng S, Luo Y, Wang B. Exosome theranostics: biology and translational medicine. Theranostics. 2018;8(1):237–255. doi:10.7150/thno.2194529290805
  • Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007;9(6):654–659. doi:10.1038/ncb159617486113
  • Cheng J, Meng J, Zhu L, Peng Y. Exosomal noncoding RNAs in Glioma: biological functions and potential clinical applications. Mol Cancer. 2020;19(1):66. doi:10.1186/s12943-020-01189-332213181
  • Farooqi AA, Desai NN, Qureshi MZ, et al. Exosome biogenesis, bioactivities and functions as new delivery systems of natural compounds. Biotechnol Adv. 2018;36(1):328–334. doi:10.1016/j.biotechadv.2017.12.01029248680
  • Abels ER, Breakefield XO. Introduction to extracellular vesicles: biogenesis, RNA cargo selection, content, release, and uptake. Cell Mol Neurobiol. 2016;36(3):301–312. doi:10.1007/s10571-016-0366-z27053351
  • Horibe S, Tanahashi T, Kawauchi S, Murakami Y, Rikitake Y. Mechanism of recipient cell-dependent differences in exosome uptake. BMC Cancer. 2018;18(1):47. doi:10.1186/s12885-017-3958-129306323
  • Ren R, Tan X-H, Zhao J-H, et al. Bone marrow mesenchymal stem cell-derived exosome uptake and retrograde transport can occur at peripheral nerve endings. Artif Cells, Nanomed Biotechnol. 2019;47(1):2918–2929. doi:10.1080/21691401.2019.164071331317777
  • McKay TB, Hutcheon AEK, Zieske JD, Ciolino JB. Extracellular vesicles secreted by corneal epithelial cells promote myofibroblast differentiation. Cells. 2020;9(5):1080. doi:10.3390/cells9051080
  • Samaeekia R, Rabiee B, Putra I, et al. Effect of human corneal mesenchymal stromal cell-derived exosomes on corneal epithelial wound healing. Invest Ophthalmol Vis Sci. 2018;59(12):5194–5200. doi:10.1167/iovs.18-2480330372747
  • Mead B, Tomarev S. Bone marrow-derived mesenchymal stem cells-derived exosomes promote survival of retinal ganglion cells through miRNA-dependent mechanisms. Stem Cells Transl Med. 2017;6(4):1273–1285. doi:10.1002/sctm.16-042828198592
  • Thery 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 Extracell Vesicles. 2018;7(1):1535750. doi:10.1080/20013078.2018.153575030637094
  • Tkach M, Kowal J, Thery C. Why the need and how to approach the functional diversity of extracellular vesicles. Philos Trans R Soc Lond B Biol Sci. 2018;373(1737):20160479. doi:10.1098/rstb.2016.047929158309
  • Witwer KW, Thery C. Extracellular vesicles or exosomes? On primacy, precision, and popularity influencing a choice of nomenclature. J Extracell Vesicles. 2019;8(1):1648167. doi:10.1080/20013078.2019.164816731489144
  • Li P, Kaslan M, Lee SH, Yao J, Gao Z. Progress in exosome isolation techniques. Theranostics. 2017;7(3):789–804. doi:10.7150/thno.1813328255367
  • Lucchetti D, Fattorossi A, Sgambato A. Extracellular vesicles in oncology: progress and pitfalls in the methods of isolation and analysis. Biotechnol J. 2019;14(1):e1700716. doi:10.1002/biot.20170071629878510
  • Théry C, Amigorena S, Raposo G, Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Current Protocols Cell Biol. 2006;Unit 3.22. doi:10.1002/0471143030.cb0322s30
  • Purushothaman A. Exosomes from cell culture-conditioned medium: isolation by ultracentrifugation and characterization. Methods Mol Biol. 2019;1952:233–244. doi:10.1007/978-1-4939-9133-4_1930825179
  • Livshits MA, Khomyakova E, Evtushenko EG, et al. Isolation of exosomes by differential centrifugation: theoretical analysis of a commonly used protocol. Sci Rep. 2015;5:17319. doi:10.1038/srep1731926616523
  • Momen-Heravi F. Isolation of extracellular vesicles by ultracentrifugation. Methods Mol Biol. 2017;1660:25–32. doi:10.1007/978-1-4939-7253-1_328828645
  • Mincheva‐Nilsson L, Baranov V, Nagaeva O, Dehlin E. Isolation and characterization of exosomes from cultures of tissue explants and cell lines. Curr Protoc Immunol. 2016;115(1):1442 1–14 42 21. doi:10.1002/cpim.17
  • Gupta S, Rawat S, Arora V, et al. An improvised one-step sucrose cushion ultracentrifugation method for exosome isolation from culture supernatants of mesenchymal stem cells. Stem Cell Res Ther. 2018;9(1):180. doi:10.1186/s13287-018-0923-029973270
  • Greening DW, Xu R, Ji H, Tauro BJ, Simpson RJ. A protocol for exosome isolation and characterization: evaluation of ultracentrifugation, density-gradient separation, and immunoaffinity capture methods. Methods Mol Biol. 2015;1295:179–209. doi:10.1007/978-1-4939-2550-6_1525820723
  • Li K, Wong DK, Hong KY, Raffai RL. Cushioned-Density Gradient Ultracentrifugation (C-DGUC): a refined and high performance method for the isolation, characterization, and use of exosomes. Methods Mol Biol. 2018;1740:69–83. doi:10.1007/978-1-4939-7652-2_729388137
  • Baranyai T, Herczeg K, Onodi Z, et al. Isolation of exosomes from blood plasma: qualitative and quantitative comparison of ultracentrifugation and size exclusion chromatography methods. PLoS One. 2015;10(12):e0145686. doi:10.1371/journal.pone.014568626690353
  • An M, Wu J, Zhu J, Lubman DM. Comparison of an optimized ultracentrifugation method versus size-exclusion chromatography for isolation of exosomes from human serum. J Proteome Res. 2018;17(10):3599–3605. doi:10.1021/acs.jproteome.8b0047930192545
  • Lobb R, Moller A. Size exclusion chromatography: a simple and reliable method for exosome purification. Methods Mol Biol. 2017;1660:105–110. doi:10.1007/978-1-4939-7253-1_928828651
  • Monguio-Tortajada M, Galvez-Monton C, Bayes-Genis A, Roura S, Borras FE. Extracellular vesicle isolation methods: rising impact of size-exclusion chromatography. Cell Mol Life Sci. 2019;76(12):2369–2382. doi:10.1007/s00018-019-03071-y30891621
  • Oksvold MP, Neurauter A, Pedersen KW. Magnetic bead-based isolation of exosomes. Methods Mol Biol. 2015;1218:465–481. doi:10.1007/978-1-4939-1538-5_2725319668
  • Soares Martins T, Catita J, Martins Rosa I, Henriques AG. Exosome isolation from distinct biofluids using precipitation and column-based approaches. PLoS One. 2018;13(6):e0198820. doi:10.1371/journal.pone.019882029889903
  • Weng Y, Sui Z, Shan Y, et al. Effective isolation of exosomes with polyethylene glycol from cell culture supernatant for in-depth proteome profiling. Analyst. 2016;141(15):4640–4646. doi:10.1039/c6an00892e27229443
  • Kalluri R. The biology and function of exosomes in cancer. J Clin Invest. 2016;126(4):1208–1215. doi:10.1172/JCI8113527035812
  • Kourembanas S. Exosomes: vehicles of intercellular signaling, biomarkers, and vectors of cell therapy. Annu Rev Physiol. 2015;77:13–27. doi:10.1146/annurev-physiol-021014-07164125293529
  • Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 2010;73(10):1907–1920. doi:10.1016/j.jprot.2010.06.00620601276
  • French KC, Antonyak MA, Cerione RA. Extracellular vesicle docking at the cellular port: extracellular vesicle binding and uptake. Semin Cell Dev Biol. 2017;67:48–55. doi:10.1016/j.semcdb.2017.01.00228104520
  • Lerner N, Chen I, Schreiber-Avissar S, Beit-Yannai E. Extracellular vesicles mediate anti-oxidative response-in vitro study in the ocular drainage system. Int J Mol Sci. 2020;21(17):6105. doi:10.3390/ijms21176105
  • Li W, Jin L, Cui Y, Nie A, Xie N, Liang G. Bone marrow mesenchymal stem cells-induced exosomal microRNA-486-3p protects against diabetic retinopathy through TLR4/NF-κB axis repression. J Endocrinol Invest. 2020. doi:10.1007/s40618-020-01405-3
  • Kurywchak P, Tavormina J, Kalluri R. The emerging roles of exosomes in the modulation of immune responses in cancer. Genome Med. 2018;10(1):23. doi:10.1186/s13073-018-0535-429580275
  • Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W. Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol. 2015;40:72–81. doi:10.1016/j.semcdb.2015.02.00925724562
  • Kim SH, Lechman ER, Bianco N, et al. Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. J Immunol. 2005;174(10):6440–6448. doi:10.4049/jimmunol.174.10.644015879146
  • Kojima M, Costantini TW, Eliceiri BP, Chan TW, Baird A, Coimbra R. Gut epithelial cell-derived exosomes trigger posttrauma immune dysfunction. J Trauma Acute Care Surg. 2018;84(2):257–264. doi:10.1097/TA.000000000000174829194317
  • Whiteside TL. Exosomes and tumor-mediated immune suppression. J Clin Invest. 2016;126(4):1216–1223. doi:10.1172/JCI8113626927673
  • Whiteside TL. Tumor-derived exosomes and their role in cancer progression. Adv Clin Chem. 2016;74:103–141. doi:10.1016/bs.acc.2015.12.00527117662
  • Knickelbein JE, Liu B, Arakelyan A, et al. Modulation of immune responses by extracellular vesicles from retinal pigment epithelium. Invest Ophthalmol Vis Sci. 2016;57(10):4101–4107. doi:10.1167/iovs.15-1835327537259
  • Chen B, Li Q, Zhao B, Wang Y. Stem cell-derived extracellular vesicles as a novel potential therapeutic tool for tissue repair. Stem Cells Transl Med. 2017;6(9):1753–1758. doi:10.1002/sctm.16-047728653443
  • Bjorge IM, Kim SY, Mano JF, Kalionis B, Chrzanowski W. Extracellular vesicles, exosomes and shedding vesicles in regenerative medicine - a new paradigm for tissue repair. Biomater Sci. 2017;6(1):60–78. doi:10.1039/c7bm00479f29184934
  • Yue Y, Garikipati VNS, Verma SK, Goukassian DA, Kishore R. Interleukin-10 deficiency impairs reparative properties of bone marrow-derived endothelial progenitor cell exosomes. Tissue Eng Part A. 2017;23(21–22):1241–1250. doi:10.1089/ten.TEA.2017.008428471299
  • Zhang S, Chuah SJ, Lai RC, Hui JHP, Lim SK, Toh WS. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials. 2018;156:16–27. doi:10.1016/j.biomaterials.2017.11.02829182933
  • Hyung S, Jeong J, Shin K, et al. Exosomes derived from chemically induced human hepatic progenitors inhibit oxidative stress induced cell death. Biotechnol Bioeng. 2020;117(9):2658–2667. doi:10.1002/bit.2744732484909
  • Hu C, Li L. Improvement of mesenchymal stromal cells and their derivatives for treating acute liver failure. J Mol Med (Berl). 2019;97(8):1065–1084. doi:10.1007/s00109-019-01804-x31197403
  • Nojima H, Freeman CM, Schuster RM, et al. Hepatocyte exosomes mediate liver repair and regeneration via sphingosine-1-phosphate. J Hepatol. 2016;64(1):60–68. doi:10.1016/j.jhep.2015.07.03026254847
  • Atienzar-Aroca S, Flores-Bellver M, Serrano-Heras G, et al. Oxidative stress in retinal pigment epithelium cells increases exosome secretion and promotes angiogenesis in endothelial cells. J Cell Mol Med. 2016;20(8):1457–1466. doi:10.1111/jcmm.1283426999719
  • Barile L, Vassalli G. Exosomes: therapy delivery tools and biomarkers of diseases. Pharmacol Ther. 2017;174:63–78. doi:10.1016/j.pharmthera.2017.02.02028202367
  • Li Y, Zheng Q, Bao C, et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res. 2015;25(8):981–984. doi:10.1038/cr.2015.8226138677
  • Xiao Y, Li Y, Yuan Y, et al. The potential of exosomes derived from colorectal cancer as a biomarker. Clin Chim Acta. 2019;490:186–193. doi:10.1016/j.cca.2018.09.00730194933
  • Melo SA, Luecke LB, Kahlert C, et al. Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature. 2015;523(7559):177–182. doi:10.1038/nature1458126106858
  • Brinton LT, Sloane HS, Kester M, Kelly KA. Formation and role of exosomes in cancer. Cell Mol Life Sci. 2015;72(4):659–671. doi:10.1007/s00018-014-1764-325336151
  • Hesari A, Golrokh Moghadam SA, Siasi A, et al. Tumor-derived exosomes: potential biomarker or therapeutic target in breast cancer? J Cell Biochem. 2018;119(6):4236–4240. doi:10.1002/jcb.2636428833502
  • Skotland T, Ekroos K, Kauhanen D, et al. Molecular lipid species in urinary exosomes as potential prostate cancer biomarkers. Eur J Cancer. 2017;70:122–132. doi:10.1016/j.ejca.2016.10.01127914242
  • Dismuke WM, Challa P, Navarro I, Stamer WD, Liu Y. Human aqueous humor exosomes. Exp Eye Res. 2015;132:73–77. doi:10.1016/j.exer.2015.01.01925619138
  • Liu Y, Bailey JC, Helwa I, et al. A common variant in MIR182 is associated with primary open-angle glaucoma in the NEIGHBORHOOD consortium. Invest Opthalmol Visual Sci. 2016;57(10):4528. doi:10.1167/iovs.16-19688
  • 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. Transl Vis Sci Technol. 2018;7(3):6. doi:10.1167/tvst.7.3.6
  • Klingeborn M, Dismuke WM, Skiba NP, Kelly U, Stamer WD, Bowes Rickman C. Directional exosome proteomes reflect polarity-specific functions in retinal pigmented epithelium monolayers. Sci Rep. 2017;7(1):4901. doi:10.1038/s41598-017-05102-928687758
  • Kang GY, Bang JY, Choi AJ, et al. Exosomal proteins in the aqueous humor as novel biomarkers in patients with neovascular age-related macular degeneration. J Proteome Res. 2014;13(2):581–595. doi:10.1021/pr400751k24400796
  • Klingeborn M, Skiba NP, Stamer WD, Bowes Rickman C. Isolation of retinal exosome biomarkers from blood by targeted immunocapture. Adv Exp Med Biol. 2019;1185:21–25. doi:10.1007/978-3-030-27378-1_431884583
  • Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin. 2017;38(6):754–763. doi:10.1038/aps.2017.1228392567
  • Ran N, Gao X, Dong X, et al. Effects of exosome-mediated delivery of myostatin propeptide on functional recovery of mdx mice. Biomaterials. 2020;236:119826. doi:10.1016/j.biomaterials.2020.11982632028167
  • Gao X, Ran N, Dong X, et al. Anchor peptide captures, targets, and loads exosomes of diverse origins for diagnostics and therapy. Sci Transl Med. 2018;10(444):eaat0195. doi:10.1126/scitranslmed.aat019529875202
  • Sterzenbach U, Putz U, Low LH, Silke J, Tan SS, Howitt J. Engineered exosomes as vehicles for biologically active proteins. Mol Ther. 2017;25(6):1269–1278. doi:10.1016/j.ymthe.2017.03.03028412169
  • Chen R, Huang H, Liu H, et al. Friend or Foe? Evidence indicates endogenous exosomes can deliver functional gRNA and Cas9 protein. Small. 2019;15(38):e1902686. doi:10.1002/smll.20190268631271518
  • Wang QL, Zhuang X, Sriwastva MK, et al. Blood exosomes regulate the tissue distribution of grapefruit-derived nanovector via CD36 and IGFR1 pathways. Theranostics. 2018;8(18):4912–4924. doi:10.7150/thno.2760830429877
  • Wassmer SJ, Carvalho LS, Gyorgy B, Vandenberghe LH, Maguire CA. Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection. Sci Rep. 2017;7:45329. doi:10.1038/srep4532928361998
  • Zhang W, Wang Y, Kong Y. Exosomes derived from mesenchymal stem cells modulate miR-126 to ameliorate hyperglycemia-induced retinal inflammation via targeting HMGB1. Invest Ophthalmol Vis Sci. 2019;60(1):294–303. doi:10.1167/iovs.18-2561730657854
  • Fu W, Lei C, Liu S, et al. CAR exosomes derived from effector CAR-T cells have potent antitumour effects and low toxicity. Nat Commun. 2019;10(1):4355. doi:10.1038/s41467-019-12321-331554797
  • Chen L, Feng Z, Yue H, et al. Exosomes derived from HIV-1-infected cells promote growth and progression of cancer via HIV TAR RNA. Nat Commun. 2018;9(1):4585. doi:10.1038/s41467-018-07006-230389917
  • Barclay RA, Schwab A, DeMarino C, et al. Exosomes from uninfected cells activate transcription of latent HIV-1. J Biol Chem. 2017;292(28):11682–11701. doi:10.1074/jbc.M117.79352128536264
  • Cho YE, Seo W, Kim DK, et al. Exogenous exosomes from mice with acetaminophen-induced liver injury promote toxicity in the recipient hepatocytes and mice. Sci Rep. 2018;8(1):16070. doi:10.1038/s41598-018-34309-730375433
  • Gao M, Dong Z, Sun J, et al. Liver-derived exosome-laden lncRNA MT1DP aggravates cadmium-induced nephrotoxicity. Environ Pollut. 2020;258:113717. doi:10.1016/j.envpol.2019.11371731864927
  • Sardar Sinha M, Ansell-Schultz A, Civitelli L, et al. Alzheimer’s disease pathology propagation by exosomes containing toxic amyloid-beta oligomers. Acta Neuropathol. 2018;136(1):41–56. doi:10.1007/s00401-018-1868-129934873
  • Huang C, Fisher KP, Hammer SS, Navitskaya S, Blanchard GJ, Busik JV. Plasma exosomes contribute to microvascular damage in diabetic retinopathy by activating the classical complement pathway. Diabetes. 2018;67(8):1639–1649. doi:10.2337/db17-158729866771
  • Ke Y, Fan X, Rui H, et al. Exosomes derived from RPE cells under oxidative stress mediate inflammation and apoptosis of normal RPE cells through Apaf1/caspase-9 axis. J Cell Biochem. 2020;121(12):4849–4861. doi:10.1002/jcb.29713
  • Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol. 2015;4:180–183. doi:10.1016/j.redox.2015.01.00225588755
  • Chettimada S, Lorenz DR, Misra V, et al. Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy. Sci Rep. 2018;8(1):7227. doi:10.1038/s41598-018-25515-429740045
  • Xiao J, Pan Y, Li XH, et al. Cardiac progenitor cell-derived exosomes prevent cardiomyocytes apoptosis through exosomal miR-21 by targeting PDCD4. Cell Death Dis. 2016;7(6):e2277. doi:10.1038/cddis.2016.18127336721
  • Saeed-Zidane M, Linden L, Salilew-Wondim D, et al. Cellular and exosome mediated molecular defense mechanism in bovine granulosa cells exposed to oxidative stress. PLoS One. 2017;12(11):e0187569. doi:10.1371/journal.pone.018756929117219
  • Hanus J, Anderson C, Wang S. RPE necroptosis in response to oxidative stress and in AMD. Ageing Res Rev. 2015;24(Pt B):286–298. doi:10.1016/j.arr.2015.09.00226369358
  • 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):2865–2883. doi:10.1042/CS2017124629203723
  • Datta S, Cano M, Ebrahimi K, Wang L, Handa JT. The impact of oxidative stress and inflammation on RPE degeneration in non-neovascular AMD. Prog Retin Eye Res. 2017;60:201–218. doi:10.1016/j.preteyeres.2017.03.00228336424
  • Stitt AW, Curtis TM, Chen M, et al. The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res. 2016;51:156–186. doi:10.1016/j.preteyeres.2015.08.00126297071
  • Wong TY, Cheung CM, Larsen M, Sharma S, Simo R. Diabetic retinopathy. Nat Rev Dis Primers. 2016;2:16012. doi:10.1038/nrdp.2016.1227159554
  • Walker R. Diabetic retinopathy: protecting the vision of people with diabetes. Br J Community Nurs. 2004;9(12):545–547. doi:10.12968/bjcn.2004.9.12.1724515655491
  • Mu H, Wang Y, Wei H, et al. Collagen peptide modified carboxymethyl cellulose as both antioxidant drug and carrier for drug delivery against retinal ischaemia/reperfusion injury. J Cell Mol Med. 2018;22(10):5008–5019. doi:10.1111/jcmm.1376830030883
  • Liu L, Sun Q, Wang R, et al. Methane attenuates retinal ischemia/reperfusion injury via anti-oxidative and anti-apoptotic pathways. Brain Res. 2016;1646:327–333. doi:10.1016/j.brainres.2016.05.03727208496
  • Moisseiev E, Anderson JD, Oltjen S, et al. Protective effect of intravitreal administration of exosomes derived from mesenchymal stem cells on retinal ischemia. Curr Eye Res. 2017;42(10):1358–1367. doi:10.1080/02713683.2017.131949128636406
  • Tokarz A, Szuścik I, Kuśnierz-Cabala B, et al. Extracellular vesicles participate in the transport of cytokines and angiogenic factors in diabetic patients with ocular complications. Folia Med Cracov. 2015;55(4):35–48.
  • Maisto R, Trotta MC, Petrillo F, et al. Resolvin D1 modulates the intracellular VEGF-related miRNAs of retinal photoreceptors challenged with high glucose. Front Pharmacol. 2020;11:235. doi:10.3389/fphar.2020.0023532210819
  • Liu C, Ge HM, Liu BH, et al. Targeting pericyte-endothelial cell crosstalk by circular RNA-cPWWP2A inhibition aggravates diabetes-induced microvascular dysfunction. Proc Natl Acad Sci U S A. 2019;116(15):7455–7464. doi:10.1073/pnas.181487411630914462
  • Zhang W, Dong X, Wang T, Kong Y. Exosomes derived from platelet-rich plasma mediate hyperglycemia-induced retinal endothelial injury via targeting the TLR4 signaling pathway. Exp Eye Res. 2019;189:107813. doi:10.1016/j.exer.2019.10781331560926
  • Kamalden TA, Macgregor-Das AM, Kannan SM, et al. Exosomal MicroRNA-15a transfer from the pancreas augments diabetic complications by inducing oxidative stress. Antioxid Redox Signal. 2017;27(13):913–930. doi:10.1089/ars.2016.684428173719
  • Katome T, Namekata K, Mitamura Y, et al. Expression of intraocular peroxisome proliferator-activated receptor gamma in patients with proliferative diabetic retinopathy. J Diabetes Complications. 2015;29(2):275–281. doi:10.1016/j.jdiacomp.2014.10.01025468312
  • 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. Nanomaterials (Basel). 2018;5. doi:10.3390/nano8050310
  • Tong Y, Zhou YL, Wang YX, Zhao PQ, Wang ZY. Retinal pigment epithelium cell-derived exosomes: possible relevance to CNV in wet-age related macular degeneration. Med Hypotheses. 2016;97:98–101. doi:10.1016/j.mehy.2016.10.02727876140
  • Shah N, Ishii M, Brandon C, et al. Extracellular vesicle-mediated long-range communication in stressed retinal pigment epithelial cell monolayers. Biochimica Et Biophysica Acta Mol Basis Dis. 2018;1864(8):2610–2622. doi:10.1016/j.bbadis.2018.04.016
  • Hajrasouliha AR, Jiang G, Lu Q, et al. Exosomes from retinal astrocytes contain antiangiogenic components that inhibit laser-induced choroidal neovascularization. J Biol Chem. 2013;288(39):28058–28067. doi:10.1074/jbc.M113.47076523926109
  • Atienzar-Aroca S, Serrano-Heras G, Freire Valls A, et al. Role of retinal pigment epithelium-derived exosomes and autophagy in new blood vessel formation. J Cell Mol Med. 2018;22(11):5244–5256. doi:10.1111/jcmm.1373030133118
  • Wang AL, Lukas TJ, Yuan M, Du N, Tso MO, Neufeld AH. Autophagy, exosomes and drusen formation in age-related macular degeneration. Autophagy. 2009;5(4):563–564. doi:10.4161/auto.5.4.816319270489
  • Aboul Naga SH, Dithmer M, Chitadze G, et al. Intracellular pathways following uptake of bevacizumab in RPE cells. Exp Eye Res. 2015;131:29–41. doi:10.1016/j.exer.2014.12.01025533679
  • Elbay A, Ercan Ç, Akbaş F, Bulut H, Ozdemir H. Three new circulating microRNAs may be associated with wet age-related macular degeneration. Scand J Clin Lab Invest. 2019;79(6):388–394. doi:10.1080/00365513.2019.163793131277558
  • Biasutto L, Chiechi A, Couch R, Liotta LA, Espina V. Retinal pigment epithelium (RPE) exosomes contain signaling phosphoproteins affected by oxidative stress. Exp Cell Res. 2013;319(13):2113–2123. doi:10.1016/j.yexcr.2013.05.00523669273
  • Bai L, Shao H, Wang H, et al. Effects of mesenchymal stem cell-derived exosomes on experimental autoimmune uveitis. Sci Rep. 2017;7(1):4323. doi:10.1038/s41598-017-04559-y28659587
  • Harrell CR, Simovic Markovic B, Fellabaum C, et al. Therapeutic potential of mesenchymal stem cell-derived exosomes in the treatment of eye diseases. Adv Exp Med Biol. 2018;1089:47–57. doi:10.1007/5584_2018_21929774506
  • Davis BM, Crawley L, Pahlitzsch M, Javaid F, Cordeiro MF. Glaucoma: the retina and beyond. Acta Neuropathol. 2016;132(6):807–826. doi:10.1007/s00401-016-1609-227544758
  • Razeghinejad MR, Myers JS, Katz LJ. Iatrogenic glaucoma secondary to medications. Am J Med. 2011;124(1):20–25. doi:10.1016/j.amjmed.2010.08.01121092926
  • Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311(18):1901–1911. doi:10.1001/jama.2014.319224825645
  • Casson RJ, Chidlow G, Wood JP, Crowston JG, Goldberg I. Definition of glaucoma: clinical and experimental concepts. Clin Exp Ophthalmol. 2012;40(4):341–349. doi:10.1111/j.1442-9071.2012.02773.x22356435
  • Almasieh M, Wilson A, Morquette B, Cueva Vargas J, Di Polo A. The molecular basis of retinal ganglion cell death in glaucoma. Prog Retin Eye Res. 2012;31(2):152–181. doi:10.1016/j.preteyeres.2011.11.00222155051
  • Harrell CR, Fellabaum C, Arsenijevic A, Markovic BS, Djonov V, Volarevic V. Therapeutic potential of mesenchymal stem cells and their secretome in the treatment of glaucoma. Stem Cells Int. 2019;2019:1–11. doi:10.1155/2019/7869130
  • 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 Cell Mol Med. 2020;24(8):4646–4658. doi:10.1111/jcmm.1512932168427
  • Lerner N, Avissar S, Beit-Yannai E. Extracellular vesicles mediate signaling between the aqueous humor producing and draining cells in the ocular system. PLoS One. 2017;12(2):e0171153. doi:10.1371/journal.pone.017115328241021
  • Liu Y, Allingham RR, Qin X, et al. Gene expression profile in human trabecular meshwork from patients with primary open-angle glaucoma. Invest Opthalmol Visual Sci. 2013;54(9):6382. doi:10.1167/iovs.13-12128
  • Stamer WD, Hoffman EA, Luther JM, Hachey DL, Schey KL. Protein profile of exosomes from trabecular meshwork cells. J Proteomics. 2011;74(6):796–804. doi:10.1016/j.jprot.2011.02.02421362503
  • Mead B, Ahmed Z, Tomarev S. Mesenchymal stem cell-derived small extracellular vesicles promote neuroprotection in a genetic DBA/2J mouse model of glaucoma. Invest Ophthalmol Vis Sci. 2018;59(13):5473–5480. doi:10.1167/iovs.18-2531030452601
  • 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 Chem Neuroanat. 2019;96:134–139. doi:10.1016/j.jchemneu.2019.01.00630639447
  • Coulson-Thomas VJ, Caterson B, Kao WWY. Transplantation of human umbilical mesenchymal stem cells cures the corneal defects of mucopolysaccharidosis VII mice. Stem Cells. 2013;31(10):2116–2126. doi:10.1002/stem.148123897660
  • Han KY, Dugas-Ford J, Seiki M, Chang JH, Azar DT. Evidence for the Involvement of MMP14 in MMP2 processing and recruitment in exosomes of corneal fibroblasts. Invest Ophthalmol Vis Sci. 2015;56(9):5323–5329. doi:10.1167/iovs.14-1441725015352
  • Kong L, Fry M, Al-Samarraie M, Gilbert C, Steinkuller PG. An update on progress and the changing epidemiology of causes of childhood blindness worldwide. J AAPOS. 2012;16(6):501–507. doi:10.1016/j.jaapos.2012.09.00423237744
  • Fulton AB, Hansen RM, Moskowitz A, Akula JD. The neurovascular retina in retinopathy of prematurity. Prog Retin Eye Res. 2009;28(6):452–482. doi:10.1016/j.preteyeres.2009.06.00319563909
  • Hansen RM, Moskowitz A, Akula JD, Fulton AB. The neural retina in retinopathy of prematurity. Prog Retin Eye Res. 2017;56:32–57. doi:10.1016/j.preteyeres.2016.09.00427671171
  • Hellström A, Smith LEH, Dammann O. Retinopathy of prematurity. The Lancet. 2013;382(9902):1445–1457. doi:10.1016/s0140-6736(13)60178-6
  • Xu W, Wu Y, Hu Z, et al. Exosomes from microglia attenuate photoreceptor injury and neovascularization in an animal model of retinopathy of prematurity. Mol Ther Nucleic Acids. 2019;16:778–790. doi:10.1016/j.omtn.2019.04.02931163320
  • Salter MW, Beggs S. Sublime microglia: expanding roles for the guardians of the CNS. Cell. 2014;158(1):15–24. doi:10.1016/j.cell.2014.06.00824995975
  • Ebneter A, Kokona D, Schneider N, Zinkernagel MS. Microglia activation and recruitment of circulating macrophages during ischemic experimental branch retinal vein occlusion. Invest Ophthalmol Vis Sci. 2017;58(2):944–953. doi:10.1167/iovs.16-2047428170538
  • Lande K, Gupta J, Ranjan R, et al. Exosomes: insights from retinoblastoma and other eye cancers. Int J Mol Sci. 2020;21(19). doi:10.3390/ijms21197055
  • Chattopadhyay C, Kim DW, Gombos DS, et al. Uveal melanoma: from diagnosis to treatment and the science in between. Cancer. 2016;122(15):2299–2312. doi:10.1002/cncr.2972726991400
  • Carvajal RD, Schwartz GK, Tezel T, Marr B, Francis JH, Nathan PD. Metastatic disease from uveal melanoma: treatment options and future prospects. Br J Ophthalmol. 2017;101(1):38–44. doi:10.1136/bjophthalmol-2016-30903427574175
  • Eldh M, Olofsson Bagge R, Lässer C, et al. MicroRNA in exosomes isolated directly from the liver circulation in patients with metastatic uveal melanoma. BMC Cancer. 2014;14:962. doi:10.1186/1471-2407-14-96225510783
  • Ragusa M, Barbagallo C, Statello L, et al. miRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma patients: pathological and diagnostic implications. Cancer Biol Ther. 2015;16(9):1387–1396. doi:10.1080/15384047.2015.104602125951497