Protective Effect of Intravitreal Administration of Exosomes Derived from Mesenchymal Stem Cells on Retinal Ischemia

Purpose: Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. Methods:...

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Vydáno v:Current eye research Ročník 42; číslo 10; s. 1358 - 1367
Hlavní autoři: Moisseiev, Elad, Anderson, Johnathon D., Oltjen, Sharon, Goswami, Mayank, Zawadzki, Robert J., Nolta, Jan A., Park, Susanna S.
Médium: Journal Article
Jazyk:angličtina
Vydáno: England Taylor & Francis 03.10.2017
Témata:
Angiogenesis
Animals
Animals, Newborn
Disease Models, Animal
exosomes
Exosomes - transplantation
Fluorescein Angiography
Humans
Intravitreal Injections
Ischemia - physiopathology
Ischemia - prevention & control
Male
mesenchymal stem cells
Mesenchymal Stem Cells - cytology
Mice
Mice, Inbred C57BL
Oxygen - toxicity
oxygen induced retinopathy
Proteomics
retinal ischemia
Retinal Neovascularization - diagnosis
Retinal Neovascularization - physiopathology
Retinal Neovascularization - prevention & control
Retinal Vessels - physiopathology
Retinopathy of Prematurity - diagnosis
Retinopathy of Prematurity - physiopathology
Retinopathy of Prematurity - prevention & control
Tomography, Optical Coherence
Angiogenesis
retinal ischemia
exosomes
mesenchymal stem cells
oxygen induced retinopathy
ISSN:0271-3683, 1460-2202, 1460-2202
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Shrnutí:Purpose: Exosomes derived from human mesenchymal stem cells (hMSCs) cultured under hypoxic conditions contain proteins and growth factors that promote angiogenesis. This study investigated the effect of intravitreal administration of these exosomes on retinal ischemia using a murine model. Methods: Oxygen-induced retinopathy (OIR) was induced by exposing one-week-old male C57BL/6J mice to 5 days of 75% hyperoxic conditioning, and returning to room air. After hyperoxic conditioning, the right eye of each mouse was injected intravitreally with 1 µl saline or exosomes derived from hMSCs and compared to control mice of the same age raised in room air without OIR injected intravitreally with saline. Two weeks post-injection, fluorescein angiography (FA) and phase-variance optical coherence tomography angiography (pvOCTA) were used to assess retinal perfusion. Retinal thickness was determined by OCT. The extent of retinal neovascularization was quantitated histologically by counting vascular nuclei on the retinal surface. Results: Among eyes with OIR, intravitreal exosome treatment partially preserved retinal vascular flow in vivo and reduced associated retinal thinning; retinal thickness on OCT was 111.1 ± 7.4µm with saline versus 132.1 ± 11.6µm with exosome, p < 0.001. Retinal neovascularization among OIR eyes was reduced with exosome treatment when compared to saline-treated eyes (7.75 ± 3.68 versus 2.68 ± 1.35 neovascular nuclei per section, p < 0.0001). No immunogenicity or ocular/systemic adverse effect was associated with intravitreal exosome treatment. Conclusions: Intravitreal administration of exosomes derived from hMSCs was well tolerated without immunosuppression and decreased the severity of retinal ischemia in this murine model. This appealing novel non-cellular therapeutic approach warrants further exploration.
Bibliografie:ObjectType-Article-1
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ISSN:0271-3683
1460-2202
1460-2202
DOI:10.1080/02713683.2017.1319491