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Title: Effects of a selective glucocorticoid receptor agonist on experimental keratoplasty. Author: Pleyer U, Yang J, Knapp S, Schäcke H, Schmees N, Orlic N, Otasevic L, De Ruijter M, Ritter T, Keipert S. Journal: Graefes Arch Clin Exp Ophthalmol; 2005 May; 243(5):450-5. PubMed ID: 15821926. Abstract: 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.[Abstract] [Full Text] [Related] [New Search]