Abstract
Purpose :
Mild traumatic brain (mTBI) injury is commonly experienced in battlefield, accidents and full contact sports, which affect vision. Inflammation-induced neurodegeneration is expected to play a major role in such visual deficits. In this study, we hypothesized that anti-inflammatory proteins released by adipose-derived stem cells (ADSC) can rescue retinal damage and improve visual function.
Methods :
About 12 weeks old C57Bl/6 mice were subjected to 50-psi air pulse on the left side of the head, resulting in an mTBI. Sham-blast mice served as control. After blast injury, 1 µl of human ASDC conditioned medium (ADSC-CM) was delivered intravitreally. One month following injection, ocular function was assessed followed by immunohistological analysis. Efficacy of ADSC-CM in normalizing retinal vascular permeability was assessed by means of trans-endothelial resistance (TER) in the presence of TNF-α (1 ng/mL).
Results :
Blast injury mice demonstrated decrease in visual acuity compared to the sham (0.302±0.01 v/s 0.39±0.01 c/d, p<0.001), with a significant improvement observed with ADSC-CM (0.376±0.007 c/d, p<0.001). Similarly, the contrast sensitivity of blast mice showed an increase in the contrast needed to detect 0.042 c/d (79.09±11.62 v/s 4.73±0.41, p<0.0001), with a significant improvement observed with ADSC-CM (79.09±11.62 v/s 41.23±8.42, p<0.001). Blast injury also resulted in a decrease in “b” wave amplitude compared to sham (368.2±40 v/s Blast, 409±33.5 mV, 25cd.s.m2 flash intensity, p<0.04), and improved by ADSC-CM, though it did not reach statistical significance (428.7±47.3 mV, p>0.05). Immunohistological analysis of retina demonstrated increased expression of GFAP in blast group as compared to sham with a reduction observed with ADSC-CM (p<0.04). Retinal endothelial cells exposed to TNF-α showed a reduction in barrier integrity as evidenced by decreased TER (TNF, 0.399±0.03; Control, 1.0±0.0 A.U., p<0.02), which was rescued with ADSC-CM (0.596±0.04 A.U., p<0.03).
Conclusions :
Our studies suggest that blast injury leads to increased retinal degeneration, which could be ameliorated by ADSC-CM possibly through glial deactivation. Future studies are needed to explore the relationship of anti-inflammatory factors secreted in ADSC-CM with glial activation as a possible mechanism of the observed therapeutic benefit in blast-associated visual deficits.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.