Abstract
Purpose :
Regulatory T cells (Tregs) are well-known to play an essential role in neuroinflammatory conditions. However, their role in visual deficits after military-relevant neurotrauma is not known. This study aims to decipher the role of CD4+ Tregs in the development of visual deficits in a mild traumatic brain injury (mTBI) mouse model.
Methods :
DEREG transgenic mice underwent Foxp3+ Treg cell ablation using Diphtheria toxin (DT, 0.05 μg/g body weight, administered IP) three days before blast injury. DT was administered every three days to sustain Treg cell depletion until 30 days post-blast injury. Mice were subjected to a 50-psi air pulse on the left side of the head, resulting in an mTBI. Mice receiving no DT served as Treg control, with sham-blast mice serving as additional controls for blast injury. One month following the injury, ocular function was assessed, followed by immunohistological analysis.
Results :
In DEREG mice, intraperitoneal DT efficiently depleted Foxp3+ Tregs in sham blast mice (8.7±1.3 vs. 14.9±3.5, p<0.03) with similar changes in blast mice (9.4±1.0 vs. 14.7±2.9, p<0.02). Blast injury mice without DT exhibited reduced visual acuity compared with the sham group (0.328±0.01 v/s 0.375±0.02 c/d, p=0.05), further decreased with DT treatment (0.290±0.01 c/d, p=0.05). Contrast sensitivity increased in blast mice without DT (44.6±7.63 v/s 20.3±0.7.3, p=0.02), further increased with DT treatment (79.8±7.64, p=0.001). Blast injury also resulted in a decrease in “b” wave amplitude compared to sham mice (87.9±12.6 v/s 137.8±14.3 mV, 1 cd.s.m2 flash intensity), further decreased with DT treatment, though it did not reach statistical significance (80.6±9.3, mV, p>0.05). Retinal GFAP expression increased in blast group without DT, worsening with DT (not statistically significant).
Conclusions :
Our studies suggest that depletion of Treg cells followed by blast injury leads to increased retinal degeneration and neuro-inflammation. This highlights the continuous requirement of Foxp3+ Treg cell activity to prevent neurodegeneration in mTBI. Future studies will fully explore the relationship of immunomodulatory Treg cells with neurodegeneration in blast-associated visual deficits. Therapeutics aiming to modulate Treg cells could be tested in DEREG blast mice.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.