Page 50 - Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine

Int J Ophthalmol, Vol. 13, No. 9, Sep.18, 2020 www.ijo.cn
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dependent diabetes, is an autoimmune disease. According to a retinal ischemia, which leads to a large number of vulnerable
study by Nojehdehi et al , explanted adipose mesenchymal neovascularization growth, resulting in a series of serious
[15]
stem cells exosomes (AMSC-Exo) from rats in a ureazide- clinical symptoms (such as fundus hemorrhage). Surgery and
induced model of T1DM were compared to control group. drug treatment cannot fundamentally solve the growth of
Rat blood glucose levels remained stable. In the study, they new blood vessels in the fundus. At present, it is believed that
found that levels of TGF-β, IL-4, and IL-10 were significantly exosomes can be used not only as a biomarker, but also as an
increased in AMSC-Exo treated rats, while IL-17 and effective therapeutic target for neovascularization .
[24]
interferon-γ levels were decreased. The conclusion of the Exosomes and Eye Diseases
Nojehdehi et al experiment is that AMSC-Exo plays a role Exosomes and autoimmune diseases of the eye The eyeball
[15]
in stabilizing T1DM blood glucose levels by increasing the acts as a visual function organ with immune gratification
regulatory T cell types and their products. Autoimmune uveitis characteristics, and its immune regulation process is extremely
[25]
is one of the main causes of vision decline in young women. complicated . This immune privilege feature removes both
Generally, long-term hormone or immunosuppressive agents local pathogenic microorganisms and protects the eye tissue
are used for treatment. These drugs have large systemic side from immune attack and ultimately affects vision. Once the
effects, and even aggravate the development of glaucoma and immune system of the eye is destroyed, various autoimmune
cataract. Therefore, new treatment methods are needed to treat diseases occur. For example, keratopathy, uveitis, Graves’
ocular autoimmune diseases. Bai et al [16] treated mice with ophthalmopathy, sympathetic ophthalmia, dry syndrome,
autoimmune uveitis by injection of MSC-exo. The results of optic neuritis, etc [26] . Liao et al [27] obtained exosomes by
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histopathological analysis showed that the number of Gr-1 ultracentrifugation of rabbit aqueous humor, and Western
granulocytes, CD4 T cells, CD68 macrophages and CD161 blot revealed that the exosomes contain a large number of
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natural killer (NK) cells in the retina decreased significantly. immunosuppressive molecules like TGF-β, thereby inhibiting
MSC-exo can inhibit the occurrence of intraocular T lymphocyte proliferation. This indicates that aqueous humor
inflammation by inhibiting the effects of CCL2 and CCL21 exosomes can effectively increase ocular immune tolerance to
chemokines. prevent ocular autoimmune diseases and reduce rejection after
Exosomes can affect angiogenesis A large number of studies corneal transplantation.
in recent years have shown that exosomes can significantly Exosomes and large area corneal damage As a kind of
promote angiogenesis. Mathiyalagan et al [17-18] and Sahoo nano vesicle, exosomes can transfer protein and RNA to
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et al [19] reported that CD34 stem cell-derived exosomes receptor cells. Studies have confirmed that human corneal
can significantly induce angiogenesis. By injecting CD34 mesenchymal cell-derived exosomes can accelerate wound
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[28]
stem cell-derived exosomes into limb ischemia mice, the healing of corneal epithelial cells , providing a new approach
[29]
level of miRNA-126-3p in the ischemic limb was increased, for the treatment of large corneal lesions. Han et al found
so as to inhibit the expression of SPRED1 and promote that mouse corneal epithelial-derived exosomes induce corneal
angiogenesis. At the same time, miRNA-126-3p can modulate myofibroblastic transformation by binding to the corneal
the gene expression involved in angiogenesis, such as cell matrix. The presence of exosomal vesicles was detected
vascular endothelial growth factor (VEGF), ANG1, ANG2, between the epithelial cells and the stroma after observation
MMP9, TSP1 etc. The study found that exosomes extracted of the damaged corneal epithelium in the rat by electron
from pericardial effusion in patients with heart failure can microscopy. However, in the uninjured rat corneal epithelium,
significantly induce therapeutic angiogenesis [20-21] . Similarly, in the presence of exosomal vesicles was not found in the same
animal models of bone defects, endothelial progenitor-derived area. By fluorescent staining, it was demonstrated that mouse
exosomes accelerate bone regeneration during distraction corneal epithelial-derived exosomes cause mouse corneal
osteogenesis by stimulating angiogenesis, whereas endothelial fibroblast proliferation by inducing α-SMA recombination.
progenitor exosomes rely primarily on miRNA-126 . Exosomes and retinopathy of prematurity Retinal tissue
[22]
Although most studies have shown that MSCs are expressed as metabolism is extremely strong, and the blood supply to
pro-angiogenic, some studies have shown that tumor-derived the inner layer is derived from the retinal blood vessels of
MSC-derived exosomes can inhibit angiogenesis by reducing the terminal branches, so ischemic lesions are highly prone
[23]
the level of VEGF , but the specific mechanism is not yet to occur. The retinal tissue is where the visual neurons are
clear. Whether the final MSCs can promote angiogenesis varies located. Once ischemia occurs, the damage to the vision is
with the microenvironment of the tumor, and the mechanism extremely serious. Among them, retinopathy of prematurity
of action is different, and the results are different. (ROP) is an ischemic neovascularization disease mainly
The proliferative stage of diabetic retinopathy is mainly due to affecting premature infants. It is one of the main causes of

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