MicroRNA-based engineered mesenchymal stem cell extracellular vesicles to treat visual deficits after blast-induced trauma

Our previous studies have shown the benefit of intravitreal injection of a mesenchymal stem cell (MSC)- derived secretome to treat visual deficits in a mild traumatic brain injury (mTBI) mouse model. In this study, we have addressed whether MSC-derived extracellular vesicles (EV) overexpressing miR4...

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Bibliographic Details
Published in:Experimental eye research 2024-10, Vol.247, p.110031, Article 110031
Main Authors: Anvarinia, Yasaman, Del Mar, Nobel A., Awad, Ahmed M., Hossain, Shahadat, Seetharaman, Amritha TM, Ravindran, Sriram, Roth, Steven, Gangaraju, Rajashekhar
Format: Article
Language:English
Subjects:
Animals
Blast Injuries - complications
Blast Injuries - metabolism
Blast Injuries - physiopathology
Blast Injuries - therapy
Disease Models, Animal
Electroretinography
Extracellular vesicles
Extracellular Vesicles - metabolism
GFAP
Inflammation
Intravitreal Injections
Male
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal stem cells
Mesenchymal Stem Cells - metabolism
Mice
Mice, Inbred C57BL
Microglia
MicroRNAs - genetics
miRNA
Nystagmus, Optokinetic - physiology
Tomography, Optical Coherence
Vision Disorders - etiology
Vision Disorders - physiopathology
Vision Disorders - therapy
Visual Acuity - physiology
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Summary:Our previous studies have shown the benefit of intravitreal injection of a mesenchymal stem cell (MSC)- derived secretome to treat visual deficits in a mild traumatic brain injury (mTBI) mouse model. In this study, we have addressed whether MSC-derived extracellular vesicles (EV) overexpressing miR424, which particularly targets neuroinflammation, show similar benefits in the mTBI model. Adult C57BL/6 mice were subjected to a 50-psi air pulse on the left side, overlying the forebrain, resulting in mTBI. Sham-blast mice were controls. Within an hour of blast injury, 3 μl (∼7.5 × 108 particles) of miR424-EVs, native-EVs, or saline was delivered intravitreally. One month later, retinal morphology was observed through optical coherence tomography (OCT); visual function was assessed using optokinetic nystagmus (OKN) and electroretinogram (ERG), followed by immunohistological analysis. A separate study in adult mice tested the dose-response of EVs for safety. Blast injury mice with saline showed decreased visual acuity compared with the sham group (0.30 ± 0.03 vs. 0.39 ± 0.01 c/d, p 
ISSN:0014-4835
1096-0007
1096-0007
DOI:10.1016/j.exer.2024.110031