Page 38 - Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine
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Li et al. Stem Cell Research & Therapy          (2019) 10:278
            https://doi.org/10.1186/s13287-019-1372-0





             REVIEW                                                                          Open Access

            Recent advances of exosomes in immune-


            mediated eye diseases

                                                      *
            Na Li, Lu Zhao, Yankai Wei, Vicki L. Ea, Hong Nian and Ruihua Wei *


                                                              Encapsulated in a bilayer membrane, exosomes are
              Abstract
                                                              enriched in various bioactive molecules, including pro-
              Exosomes, nanosized extracellular vesicles of 30–150  teins, lipids, RNAs (mRNA, circular RNA, microRNA,
              nm, are shed by almost all cell types. Bearing proteins,  long noncoding RNA), and DNAs (genomic DNA, cDNA,
              lipids, RNAs, and DNAs, exosomes have emerged as  and mitochondrial DNA) [7–9]. These molecular compo-
              vital biological mediators in cell-to-cell      nents are capable of inducing functional responses in re-
              communication, affecting a plethora of physiological  cipient cells and are extraordinarily variable depending on
              and pathological processes. Particularly, mounting  the cellular origin and cell exposure context [10–13]. By
              evidence indicates that immunologically active  transferring these functional molecules between cells, exo-
              exosomes can regulate both innate and adaptive  somes act as potent mediators in intercellular communi-
              immune responses. Herein, we review recent      cation and participate in numerous physiological and
              advances in the research of exosomes in several  pathological processes [14]. Exosomes from both immune
              immune-mediated eye diseases, including Sjögren’s  cells and non-immune cells exert pivotal roles in the regu-
              syndrome (SS) dry eye, corneal allograft rejection,  lation of immunity [15] and have been reported to be in-
              autoimmune uveitis, and age-related macular     volved in the development and treatment of inflammatory
              degeneration (AMD). Additionally, we discuss the  and autoimmune diseases [16, 17].
              potential of exosomes as novel biomarkers and drug  The eye, a unique sensory organ of vision, is
              delivery vesicles for the diagnosis and treatment of  regarded as an immune-privileged site that prevents
              eye diseases.                                   immunogenic inflammation [18]. Still, there are sev-
                                                              eral inflammatory and immune-mediated diseases
              Keywords: Exosomes, Sjögren’s syndrome, Corneal
                                                              which involve the anterior or posterior segment of
              allograft rejection, Autoimmune uveitis, Age-related
                                                              the eye, even in severe cases resulting in sight-threat-
              macular degeneration, Biomarkers, Drug delivery
                                                              ening conditions, such as Sjögren’s syndrome (SS) dry
                                                              eye, corneal allograft rejection, uveitis, and age-related
                                                              macular degeneration (AMD) [19–21]. Of these dis-
            Introduction                                      eases, the action of immune cells and the expression
            Exosomes were first described as 50-nm diameter-sized  of pro-inflammatory cytokines and chemokines induce
            vesicles secreted from maturing sheep reticulocytes in  local inflammatory responses which ultimately cause
            the early 1980s [1, 2]. These nanovesicles sparked scien-  ocular tissue damage. Although therapeutic strategies
            tists’ interest, as they appeared to function from cellular  have undergone substantial transformation, there are
            garbage disposals to potent intercellular communication  still some challenges remaining [22, 23].
            mediators. Typically, exosomes are a subtype of extracel-  In this review, we highlight and discuss the recent
            lular vesicles (EVs) (30–150 nm) secreted by almost all  research advances about exosomes in several immune-re-
            cell types [3, 4]. They widely exist in numerous bio-  lated eye diseases and their potential as biomarkers and
            logical fluids including serum, urine, breast milk, tear  drug delivery vesicles in the eye.
            fluid, vitreous humor, saliva, and aqueous humor, under
            both healthy and pathological conditions [5, 6].
                                                              Biogenesis and function of exosomes
            * Correspondence: nianhong@126.com; rwei@tmu.edu.cn  Exosome generation starts with the invagination of the
            Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and
            School of Optometry, Tianjin Medical University Eye Hospital, No.251 Fukang  plasma membrane to form early endosomes. As the early
            Road, Nankai District, Tianjin 300384, People’s Republic of China  endosomes mature, intraluminal vesicles (ILV) are
                                     © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
                                     International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and
                                     reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
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