Related Experiment Video
Updated: Aug 18, 2026
Evaluating Therapeutic and Chemical Toxicity Using Organ-Cultured Porcine Corneas and Epithelial Wound Healing
Published on: January 10, 2025
Effects of a selective glucocorticoid receptor agonist on experimental keratoplasty
Uwe Pleyer1, Jun Yang, Sigrid Knapp
1Department of Ophthalmology, Institute of Pharmacy, Charité, Humboldt University, Berlin, Germany. uwe.pleyer@charite.de
Background:
New insights into the molecular mechanisms of corticosteroid-mediated actions have revealed new substances, such as selective glucocorticoid receptor agonists (SEGRA), for the treatment of inflammatory diseases. We set out to evaluate the effect of a SEGRA compound following topical application on the course of experimental orthotopic corneal grafts.
Methods:
A total of 42 female Lewis rats received 3.5-mm MHC I/II-incompatible corneal grafts from DA donors. Recipients were randomly assigned to receive either no therapy, 0.25% cyclodextrin-encapsulated SEGRA compound in a new microemulsion formulation or carrier system only. All treatments started on the day of surgery and were given five times daily for 35 days. Grafts were graded every day and a rejection score was generated based on cornea clarity and edema. In addition, intragraft mRNA expression of CD3, IFN-gamma, TNF-alpha, IL-10 and IL-4 was analyzed using real-time RT-PCR analysis at day 7 after transplantation before rejection occurred in additional control animals.
Results:
Topical application of a SEGRA compound was highly effective in prolonging the mean survival time of corneal grafts (42.2+/-4.0 days) compared with untreated controls (11.7+/-1.2 days, p=0.00003) or animals that received the vehicle only (15.0+/-1.5 days, p=0.114). In addition, real-time RT-PCR analysis of SEGRA-treated grafts revealed lower mRNA expression of intragraft cytokines; the difference was significant for IL-4 (p<0.05).
Conclusions:
Our results indicate that topical application of a SEGRA compound significantly prolongs corneal graft survival in an experimental keratoplasty model. It further suggests that SEGRA can be a potentially useful drug to suppress the immune response.
