Page 51 - Mesenchymal Stem Cell-Derived Exosomes as an Emerging Paradigm for Regenerative Therapy and Nano-Medicine

Function of exosomes in ocular diseases

childhood blindness in the world. Microglia is one of the cells by exosomes may lead to the formation of drusen. Recent
glia cell subtypes, which are not only inflammatory cells, but studies have shown that, exosomes secreted by RPE cells are
also involved in the development of normal blood vessels in considered to have neuroprotective effects and are closely
[35]
the retina [30] . Studies have shown that microglia exosomes related to the pathological processes of AMD .
downregulate the expression of VEGF and TGF-β in hypoxia- Exosomes and glaucoma Glaucoma is a group of diseases
induced photoreceptors in hypoxic-induced mouse optic characterized by optic atrophy, visual field defects and
neuropathy. It also reduces apoptosis and significantly inhibits decreased vision. Pathological increase in intraocular pressure
[36]
neovascularization. It was showed that the level of miRNA-24- is the main risk factor for its onset . When the intraocular
3p was extremely high in microglia exosomes, indicating that aqueous drainage loss leads to an increase in pathological
miRNA-24-3p is a key molecule that inhibits the expression intraocular pressure, the increased intraocular pressure causes
[31]
of IRE1α induced by hypoxia . It is predicted that microglia optic nerve damage through mechanical compression and
exosomes can promote the normal angiogenesis and visual optic nerve ischemia. The longer the duration of intraocular
[37]
enhancement of hypoxia-induced retinal mice, which provides pressure increase, the more severe the visual impairment .
a new idea for the treatment of ROP. Most of the pathological increase in intraocular pressure is
Exosomes and diabetic retinopathy Diabetic retinopathy caused by the outflow of aqueous humor, such as stenosis of
is one of the most common microvascular complications of the anterior chamber, trabecular sclerosis, abnormal substances
diabetes. Patients show signs of decreased vision and severe produced by extracellular matrix, and trabecular meshwork.
[38]
blindness. Recent studies have shown that the complement Tabak et al found that non-pigmented ciliary epithelial cells
system is a major player in vascular injury and diabetic exosomes (NPCE-Exo) affect trabecular meshwork cadherin
retinopathy. The complement system plays an important role by inducing Wnt signaling in trabecular meshwork cells,
in the host’s defense against infectious pathogens by activating reducing phosphorylated GSK3 and β-catenin expression. As
the inflammatory response. The complement system can be an important component of the extracellular matrix, cadherin
activated in three ways: the classical pathway, the alternative can increase the pore size of the trabecular meshwork, leading
pathway, and the lectin pathway. All three complement to an increase in the outflow resistance of the aqueous humor
[39]
activation pathways result in the production of C3/C5 and an increase in intraocular pressure. Pan et al studied
convertase and ultimately lead to the formation of membrane the role of umbilical cord mesenchymal stem cell-derived
[33]
[32]
attack complex (MAC) . Huang et al established a mouse exosomes (UMSCs-exo) in the rat model of optic nerve
model of diabetic retinopathy to demonstrate that exosomes squeezing. Through exosome tracking, immunohistochemical
containing IgG can cause retinal vascular damage by activating analysis, fluorescence microscopy, etc. UMSCs-exo can
the classical complement pathway, and the number of these promote the survival of RGC but does not promote axonal
exosomes is significantly increased in diabetic mice. However, regeneration. Staining by GFAP antibody showed that the
in diabetic mice lacking IgG exosomes, retinal vascular number of retinal glial cells treated by UMSCs-exo increased
damage is reduced. and the activity was enhanced. However, according to Mead
[40]
Exosome and age-related macular degeneration Age- and Tomarev , in the rat optic nerve crush model, BMSCs
related macular degeneration (AMD) refers to the degenerative exosomes significantly promoted the survival and axonal
lesions of the retinal tissue in the macular area over 45 years regeneration of RGCs through miRNA dependent mechanism
of age, and its prevalence increases with age. The cause of the (especially through miRNA-17-92 and miRNA 21).
disease is still unclear and may be related to heredity, chronic In conclusion, exosomes can be used as a therapeutic carrier
photodamage, nutritional disorders, poisoning, and immune to participate in multiple pathophysiological processes such
diseases. AMD could cause the central vision to gradually as immune response, angiogenesis, and nerve repair in ocular
decrease, and severe cases can cause blindness. AMD is related diseases. Research on the role of exosomes in ocular-
divided into two categories: atrophic (dry) and exudative related diseases is still in its infancy. Due to the extensive
(wet). The former is characterized by atrophy of the macular presence and accessibility of exosomes, it will become
area and formation of drusen. Many proteins (PDK1, ERK a potential way for the diagnosis and treatment of ocular
1/2, AMPKα1, acetyl CoA carboxylase, etc.) were detected in diseases.
the exosomes secreted by retinal pigment epithelium (RPE) ACKNOWLEDGEMENTS
cells by Bisutto et al . At the same time, these proteins were Foundations: Supported by the National Natural Science
[34]
also detected in the vitreous of AMD patients, suggesting an Foundation of China (No.81470633); the Natural Science
inevitable link between exosomes and AMD. An increase in Grant of the Heilongjiang Province of China (No.
related proteins such as αB crystal proteins released in RPE H2018035); the Innovation and Development Foundation

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