Abstract
Purpose :
To explore the impact of rVA576, a recombinant bifunctional protein that inhibits LTB4 and C5, when administered intravitreally or topically during active EAU.
Methods :
To induce EAU, C57B6 mice (female, 5-8 weeks old) were immunized with IRBP1-20 as previously described1. Mice were clinically scored by retinal fundoscopy and, on day 14-16 post immunization, rVA576 (0.5%) or saline was administered intravitreally. Disease progression was graded clinically by retinal fundoscopy and scored histologically. We also investigated the effect of rVA576 on CD4+ T cell subsets using retinal flow cytometry (Fortessa, BD).
Results :
We found that rVA576 mitigated disease progression at one day post intravitreal administration as determined by clinical scoring (mean score±SD; 5.167±1.327; n=6) relative to saline controls (10.33 ± 1.202; n=3; P= 0.043). A significant decrease in retinal Th17 cells in the rVA576 treated group (mean percentage±SD; 46.28±7.079; n=6) was detected relative to controls (83.33±4.842; n=3; P=0.015). A decrease in retinal double-positive Th1+Th17+ (RORγt+T-bet+) levels (40.68± 7.505; n=6) was also observed relative to controls (82.40 ± 7.969; n=3; P=0.011). In addition, decreases in RORγt+IFNγ+ cells (28.78±4.527; n=6) were detected in rVA576-treated mice in comparison with controls (51.63 ± 6.583; n=3; P=0.025) after one day post administration while there was no significant difference in the expression levels of CD4+CD25+FoxP3+ and CD4+T-bet+IFNγ+.
Conclusions :
rVA576 attenuated EAU progression which was accompanied with a decrease in Th17 and double-positive Th1+Th17+ cells. We plan to test a long-acting version of rVA576, which may offer more prolonged efficacy in murine EAU.
1 Eskandarpour M., et al., (2017)
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.