Abstract
Purpose :
We have generated a potent anti-IFN-γ aptamer and investigated its efficacy in a severe dry eye model by topical eye drop administration by inhibiting IFN-γ, in order to develop efficacious and fast acting medicine to treat severe dry eye conditions, including Sjögren’s syndrome related dry eye.
Methods :
Age- and weight-matched female mice were housed in a controlled environment room (20% relative humidity) with scopolamine administered to induce dry eye disease (DED) for 1-10 or 1-5 days. In first experiment, the mice received 10 mL eye drop administration t.i.d. TXB-0063, IFN-γ specific aptamer, (1 mg/mL) or Restasis® (0.5 mg/mL) or Xiidra® (50 mg/mL) on Days 3-9 for evaluating therapeutic efficacy by observing clinical scoring and the number of goblet cells and infiltrated CD4+ T-cells. In another experiment, the mice received 10 mL eye drop administration t.i.d. TXB-0063 (0.01 or 1 mg/mL), Restasis®, or Xiidra® on Days 1-4 for evaluating preventive and early onset efficacy by corneal damage, on Day 5. Corneal damage from DED induction was assessed by a clinical score. The CD4+ T-cells were evaluated by immunohistochemistry, and the goblet cells were evaluated by staining with periodic acid-Schiff reagent.
Results :
TXB-0063 showed a trend toward suppression of corneal damage, reduction of CD4+ T cell infiltration to the same level to the normal level, and significant improvement of goblet cell count to the normal levels during Days 3-9 treatment. On the other hand, an improvement by Restasis® and Xiidra® tested on CD4+ T cell infiltration and goblet cell count was limited. In addition, TXB-0063 had an inhibitory effect on corneal damage at Day 5, showing its early on-set of the efficacy, whereas Restasis® and Xiidra® which have been known as slow on-set drugs did not.
Conclusions :
TXB-0063, anti-IFN-γ DNA aptamer elucidated a prominent efficacy in the dry eye model by both therapeutic and preventive administration. The efficacy of TXB-0063 observed in the severe DED model was observed in an early on-set than that of Restasis® and Xiidra®, and it also improved CD4+ T cell infiltration to the same level to the normal and goblet cell count to the normal levels. These findings suggest that this innovative TXB-0063, anti-IFN-γ aptamer has a potential to be developed to treat severe DED including Sjögren’s syndrome related dry eye.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.