Abstract
Purpose :
Our previous studies have shown the benefit of intravitreal injection of 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 that particularly target neuroinflammation shows similar benefits in the mTBI model.
Methods :
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 x 108 particles) of miR424-EVs, Control-EVs, or saline was delivered intravitreally. One month later, retinal morphology was observed through OCT, ocular function was assessed using OKN and ERG, followed by immunohistological analysis.
Results :
Both Ctrl-EVs and miR424-EVs exhibited vitreous aggregation and occasional retinal detachments. Blast injury mice with saline showed decreased visual acuity compared with the sham group (0.30±0.03 v/s 0.39±0.02 c/d, p<0.001), improved with miR424-EV (0.39±0.02 c/d, p<0.01) but not Ctrl-EV (0.33±0.04 c/d, p>0.05). Contrast sensitivity of blast mice receiving saline increased compared with the sham group (85.3±5.9 v/s 19.9±4.8, p<0.001), rescued by miR424-EV (23.6±7.3 c/d, p<0.01) and Ctrl-EV (45.6±10.7 c/d, p<0.01). Blast injury decreased “b” wave amplitude compared to sham mice (94.6±24.0 v/s 279.2±25.3 mV, p<0.01), improved with miR424-EV (173±27.2 c/d, p<0.02) and Ctrl-EV (230.2±37.1 c/d, p<0.001). Immunohistology showed increased GFAP in blast mice with saline vs. sham (1.2±0.06 vs. 0.7±0.06, p<0.01), reduced only with Ctrl-EV (1.0±0.05, p<0.05), not with miR424-EV (1.1±0.09, p>0.05).
Conclusions :
Our studies suggest that EV aggregation might be of concern at the concentration tested, resulting in retinal artifacts. Despite this, miR424 and control EVs imparted significant protection against neuroinflammatory blast-related injury. Future studies must address EV aggregation or alternative non-invasive delivery modes to curtail the challenges of translating these therapies.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.