M R Dana1, J Yamada, J W Streilein. 1. Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
Abstract
BACKGROUND: Interleukin (IL)-1 is a potent proinflammatory cytokine that plays a critical role in initiating and maintaining immunogenic inflammation. We performed a series of experiments to determine whether the topical application of IL-1 receptor antagonist (IL-1ra) can prolong corneal transplant survival in the murine model of orthotopic allotransplantation. METHODS: For all experiments, C57BL/6 corneas were transplanted into BALB/c (major histocompatibility and minor histocompatibility-disparate) eyes. "High-risk" transplants were transplants that had been sutured into BALB/c recipient beds with corneal neovascularization induced by placement of three interrupted sutures in the host cornea 2 weeks earlier. Both risk groups were divided in a masked fashion into treatment subgroups that received either 20 mg/ml of IL-1ra mixed in 0.2% sodium hyaluronate vehicle (n=28) or placebo alone (n=25). All transplants were evaluated for 8 weeks after surgery for signs of rejection. At the end of follow-up, corneal specimens were processed for enumeration of Langerhans cells and histopathological evaluation. RESULTS: Survival rates of both normal-risk and high-risk transplants increased significantly among the IL-1ra-treated animals compared with untreated controls by both stratified Mantel-Haenszel (P=0.02) and Kaplan-Meier survival (P=0.03) analyses. Furthermore, both normal- and high-risk IL-1ra-treated grafts had significantly less inflammation and Langerhans cells infiltration compared with untreated controls. CONCLUSIONS: Topical treatment with IL-1ra has a significantly positive effect in promoting corneal allograft survival.
BACKGROUND:Interleukin (IL)-1 is a potent proinflammatory cytokine that plays a critical role in initiating and maintaining immunogenic inflammation. We performed a series of experiments to determine whether the topical application of IL-1 receptor antagonist (IL-1ra) can prolong corneal transplant survival in the murine model of orthotopic allotransplantation. METHODS: For all experiments, C57BL/6 corneas were transplanted into BALB/c (major histocompatibility and minor histocompatibility-disparate) eyes. "High-risk" transplants were transplants that had been sutured into BALB/c recipient beds with corneal neovascularization induced by placement of three interrupted sutures in the host cornea 2 weeks earlier. Both risk groups were divided in a masked fashion into treatment subgroups that received either 20 mg/ml of IL-1ra mixed in 0.2% sodium hyaluronate vehicle (n=28) or placebo alone (n=25). All transplants were evaluated for 8 weeks after surgery for signs of rejection. At the end of follow-up, corneal specimens were processed for enumeration of Langerhans cells and histopathological evaluation. RESULTS: Survival rates of both normal-risk and high-risk transplants increased significantly among the IL-1ra-treated animals compared with untreated controls by both stratified Mantel-Haenszel (P=0.02) and Kaplan-Meier survival (P=0.03) analyses. Furthermore, both normal- and high-risk IL-1ra-treated grafts had significantly less inflammation and Langerhans cells infiltration compared with untreated controls. CONCLUSIONS: Topical treatment with IL-1ra has a significantly positive effect in promoting corneal allograft survival.
Authors: Brant R Ward; James V Jester; Akiko Nishibu; Mridula Vishwanath; David Shalhevet; Tadashi Kumamoto; W Matthew Petroll; H Dwight Cavanagh; Akira Takashima Journal: Immunology Date: 2007-01-22 Impact factor: 7.397
Authors: Thomas H Dohlman; Antonio Di Zazzo; Masahiro Omoto; Jing Hua; Julia Ding; Pedram Hamrah; Sunil K Chauhan; Reza Dana Journal: Transplantation Date: 2016-04 Impact factor: 4.939
Authors: Pedram Hamrah; Zdenka Haskova; Andrew W Taylor; Qiang Zhang; Bruce R Ksander; M Reza Dana Journal: Transplantation Date: 2009-07-27 Impact factor: 4.939