MicroRNA-based engineered mesenchymal stem cell extracellular vesicles to treat visual deficits after blast-induced
Yasaman Anvarinia1, Nobel A Del Mar1, Ahmed M Awad2
1Department of Ophthalmology, University of Tennessee Health Science Center, 930 Madison Ave, Suite 769, Memphis, TN, 38163, USA.
Experimental Eye Research
|August 11, 2024
Summary
Mesenchymal stem cell-derived extracellular vesicles (EVs) overexpressing miR424 show promise in treating visual deficits after mild traumatic brain injury (mTBI). While effective, further research is needed to optimize EV delivery and dosage to mitigate aggregation and neuroinflammation.
Area of Science:
- Neuroscience
- Ophthalmology
- Regenerative Medicine
Background:
- Previous studies demonstrated the therapeutic potential of mesenchymal stem cell (MSC)-derived secretomes for visual deficits in mild traumatic brain injury (mTBI) mouse models.
- Extracellular vesicles (EVs) derived from MSCs are key mediators of secretome function and can be engineered for targeted delivery of therapeutic molecules like microRNAs.
Purpose of the Study:
- To investigate the efficacy of intravitreally delivered MSC-derived EVs overexpressing miR424 (miR424-EVs) in ameliorating visual dysfunction following mTBI in mice.
- To compare the therapeutic effects of miR424-EVs with native EVs and saline treatment in the mTBI model.
- To assess the safety and potential adverse effects of EV administration at the tested dosage.
Main Methods:
- Adult C57BL/6 mice were subjected to a controlled mild traumatic brain injury (mTBI) using an air pulse model.
- Intravitreal injections of miR424-EVs, native EVs, or saline were administered within one hour post-injury.
- Visual function was evaluated one month later using optical coherence tomography (OCT), optokinetic nystagmus (OKN), and electroretinogram (ERG). Immunohistological analyses were performed to assess neuroinflammation markers (GFAP, IBA1) and vascularization (αSMA, CD31).
Main Results:
- miR424-EVs significantly improved visual acuity and contrast sensitivity in mTBI mice compared to saline controls.
- Both miR424-EVs and native EVs partially rescued ERG "b" wave amplitudes and improved a-wave amplitudes, indicating functional recovery.
- While EVs reduced GFAP and IBA1 expression compared to saline, both EV types caused vitreous aggregation and increased vascular structures, with native EVs showing more pronounced effects at higher concentrations.
Conclusions:
- MSC-derived EVs, particularly miR424-EVs, demonstrate significant neuroprotective benefits and therapeutic potential for visual dysfunction after mTBI.
- EV-based therapy offers a promising avenue for treating TBI-induced visual impairments, though challenges related to aggregation and potential neuroinflammation at current dosages require further investigation.
- Optimization of EV delivery methods and dosage adjustments are crucial for enhancing therapeutic outcomes and minimizing adverse effects in future clinical applications.
