Page 44 - Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine

Li et al. Stem Cell Research & Therapy (2019) 10:278 Page 7 of 10

protein and nucleic acid contents, the research of exo- highly purified exosomes with stable functional efficacy.
some biomarkers for eye diseases appears to have suffi- Exosome research in the eye is still a relatively young
ciently hopeful prospects. field, awaiting more extensive investigations into the
precise biological mechanisms and clinical potential of
exosomes in ocular diseases.
Exosomes as drug delivery vesicles
The conventional route of treatment for eye disease,
Abbreviations
especially involving the anterior segment, is topical in-
AAV-2: Adeno-associated virus type 2; AH: Aqueous humor; AMD: Age-
stillation of eye drops, which is accompanied with limita- related macular degeneration; AQP5: Aquaporin 5; BAFF: B cell activating
tions such as the need for frequent administration and factor; BBB: Blood-brain barrier; CFH: Complement factor H; CNV: Choroidal
neovascularization; DCs: Dendritic cells; EAU: Experimental autoimmune
low bioavailability. During recent years, various synthetic
uveoretinitis; EBV: Epstein-Barr virus; ESCRT: Endosomal sorting complex
drug vehicles have been developed for encasing existing required for transport; EVs: Extracellular vesicles; FH: Factor H; FHL-1: Factor H
drugs to enhance the therapeutic effect [111]. However, like 1; HMGB1: High-mobility group box 1; hUC-MSC-Exos: Human umbilical
cord-derived MSC-Exos; IFN: Interferon; ILV: Intraluminal vesicles;
troubling issues including their immunotoxicity [112]
iNOS: Inducible nitric oxide synthase; IRBP: Interphotoreceptor retinoid-
and quick clearance by the mononuclear phagocyte sys- binding protein; LGs: Lacrimal glands; MHC: Major histocompatibility
tem (MPS) or the reticuloendothelial system (RES) [113] complex; MPS: Mononuclear phagocyte system; MSC-Exos: Mesenchymal
stem cells-derived exosomes; MSCs: Mesenchymal stem cells;
still exist. Fortunately, exosomes, regarded as natural
MVBs: Multivesicular bodies; NK: Natural killer; PD-L1: Programmed death-
nanocarriers, have plenty of the highly desired qualities ligand 1; RES: Reticuloendothelial system; RNPs: Ribonucleoproteins;
that drug delivery vehicles should have. These small ves- RPE: Retinal pigment epithelium; SGECs: Salivary gland epithelial cells;
SNARE: Soluble N-ethylmaleimide-sensitive fusion attachment protein
icles are capable of penetrating the blood-brain barrier
receptor; SNPs: Single nucleotide polymorphisms; SS: Sjögren’s syndrome;
(BBB), delivering their cargoes across cell membranes STIM1: Stromal interacting molecule 1; TLRs: Toll-like receptors;
and targeting specific cell types after artificial modifica- Tregs: Regulatory T cells; TSG101: Tumor susceptibility gene 101;
VEGF: Vascular endothelial growth factor; VH: Vitreous humor
tions [114]. Collectively, exosomes have been shown to
serve as possible nanocarriers for functional RNA
Acknowledgements
strands (mRNA, miRNA, siRNA, and lncRNA), DNA The authors would like to thank the National Natural Science Foundation of
molecules, peptides, or synthetic drugs [115, 116]. For China (81770901, 81570834), the Scientific Research Foundation for the
instance, exosomes from adeno-associated virus type 2 Returned Overseas Chinese Scholars, State Education Ministry (No. 48), and
the Tianjin Clinical Key Discipline Project (TJLCZDXKT003). The authors would
(AAV-2)-producing 293 T cells showed higher efficiency like to thank Tianjin Medical University Eye Hospital, Eye Institute, for its
in retinal transduction than conventional AAV-2 after supports in developing this paper.
intravitreal injection and were regarded as robust tools
for intravitreal gene transfer into the retina [117]. Be- Authors’ contributions
sides, MSC-Exos loaded with exogenous miRNA-126 NL read the literature related to the topic and participated in drafting the
manuscript. LZ and YW participated in searching and archived the literature
were reported to alleviate hyperglycemia-induced retinal related to the topic and discussed the contents of the manuscript. VE revised
inflammation via suppressing the high-mobility group the manuscript. HN and RW participated in the design, revision, and final
box 1 (HMGB1) signal pathway [66]. Moreover, chemo- approval of the manuscript. All authors read and approved the final
manuscript.
therapeutic drug-loaded exosomes showed higher effi-
cacy and better bioavailability compared to free drug
Authors’ information
[118, 119], which sheds new light on ocular pharma- Na Li, Postgraduate, is studying in Tianjin Key Laboratory of Retinal Functions
cotherapeutics. So far, there has been sparse research and Diseases, Eye Institute and School of Optometry, Tianjin Medical
University Eye Hospital, No. 251, Fukang Road, Nankai District, Tianjin 300384,
focused on the latent role of loading exosomes with
China. Lu Zhao, Postgraduate, is studying in Tianjin Key Laboratory of Retinal
exogenous functional cargoes in eye diseases. Therefore, Functions and Diseases, Eye Institute and School of Optometry, Tianjin
significant endeavors are needed to develop such therap- Medical University Eye Hospital, No. 251, Fukang Road, Nankai District, Tianjin
300384, China. Yankai Wei, Ph.D., candidate, is studying in Tianjin Key
ies in ophthalmology.
Laboratory of Retinal Functions and Diseases, Eye Institute and School of
Optometry, Tianjin Medical University Eye Hospital, No. 251, Fukang Road,
Nankai District, Tianjin 300384, China. Vicki L. Ea, Researcher, is working in
Conclusions Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and
Taken together, the extensive implication of exosomes School of Optometry, Tianjin Medical University Eye Hospital, No. 251,
Fukang Road, Nankai District, Tianjin 300384, China. Her research focus was
in regulating various aspects of the immunity makes
on diabetic retinopathy. Hong Nian, PhD, is a Principal Investigator in Tianjin
exosomes attractive diagnostic and therapeutic candi- Key Laboratory of Retinal Functions and Diseases, Eye Institute and School of
dates for immune-mediated eye diseases (Fig. 2). Optometry, Tianjin Medical University Eye Hospital, No. 251, Fukang Road,
Nankai District, Tianjin 300384, China. She focused on studying the
Because of their multiple functions, elucidating the
mechanisms of autoimmune diseases, including autoimmune dacryoadenitis
contents of exosomes and understanding how each of and autoimmune uveitis. Ruihua Wei, MD, Chief Consultant, is working in
them function are necessary. Additionally, for success- Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and
School of Optometry, Tianjin Medical University Eye Hospital, No. 251,
ful translation into clinical therapies, novel and
Fukang Road, Nankai District, Tianjin 300384, China. She is engaged in the
advanced technology is urgently needed to obtain mass diagnosis and treatment of ocular surface diseases and myopia.