title: Topical soluble tumor necrosis factor receptor type I suppresses ocular chemokine gene expression and rejection of allogeneic corneal transplants.
abstract: OBJECTIVE
  To determine the effect of topical soluble tumor necrosis factor receptor type I (sTNFR-I) on survival of murine orthotopic corneal transplants and on ocular chemokine gene expression after corneal transplantation.
  
  
  METHODS
  BALB/c mice (N = 50) were used as recipients of multiple minor H-disparate corneal transplants from B10.D2 donors. After orthotopic corneal transplantation, mice were randomized in a masked fashion to receive either topical sTNFR-I or vehicle 3 times daily, and all grafts were evaluated for signs of rejection and neovascularization by slitlamp biomicroscopy for 8 weeks. Ocular chemokine gene expression in sTNFR-I- and vehicle only-treated groups was determined using a multiprobe ribonuclease protection assay.
  
  
  RESULTS
  Hosts treated with topical sTNFR-I experienced significantly enhanced corneal allograft survival compared with animals treated with vehicle alone (P =.01). Moreover, postoperative messenger RNA levels of RANTES and macrophage inflammatory protein-1beta in sTNFR-I-treated eyes were substantially suppressed compared with vehicle-treated eyes. Vehicle-treated eyes bearing rejected allografts expressed higher levels of messenger RNA for both chemokines than control eyes bearing accepted allografts.
  
  
  CONCLUSIONS
  Topical treatment with sTNFR-I promotes the acceptance of allogeneic corneal transplants and inhibits gene expression of 2 chemokines (RANTES and macrophage inflammatory protein-1beta) associated with corneal graft rejection.
  
  
  CONCLUSIONS
  Our findings support the feasibility of a topical anticytokine strategy as a means of reducing corneal allograft rejection without resorting to the use of potentially toxic immunosuppressive drugs.
authors: Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
authors: Y
authors: Y
authors: Qian
authors: I
authors: I
authors: Dekaris
authors: S
authors: S
authors: Yamagami
authors: M R
authors: MR
authors: Dana
mesh_terms: D000287:Administration, Topical; D000818:Animals; D015703:Antigens, CD / Q000008:administration & dosage / Q000494:pharmacology*; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000235:genetics*; D003315:Cornea / Q000378:metabolism; D016039:Corneal Transplantation; D015870:Gene Expression / Q000187:drug effects*; D006084:Graft Rejection / Q000378:metabolism / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D019402:Macrophage Inflammatory Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D023282:Nuclease Protection Assays; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis*; D011897:Random Allocation; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage; D047888:Receptors, Tumor Necrosis Factor, Type I; D012995:Solubility; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D015703:Antigens, CD; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D009883:Ophthalmic Solutions; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha