PMID- 11115261
OWN - NLM
STAT- MEDLINE
DCOM- 20001222
LR  - 20220311
IS  - 0003-9950 (Print)
IS  - 0003-9950 (Linking)
VI  - 118
IP  - 12
DP  - 2000 Dec
TI  - Topical soluble tumor necrosis factor receptor type I suppresses ocular chemokine 
      gene expression and rejection of allogeneic corneal transplants.
PG  - 1666-71
AB  - 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. 
      CLINICAL RELEVANCE: 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.
FAU - Qian, Y
AU  - Qian Y
AD  - Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical 
      School, Boston, MA, USA.
FAU - Dekaris, I
AU  - Dekaris I
FAU - Yamagami, S
AU  - Yamagami S
FAU - Dana, M R
AU  - Dana MR
LA  - eng
GR  - NEI0363/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Arch Ophthalmol
JT  - Archives of ophthalmology (Chicago, Ill. : 1960)
JID - 7706534
RN  - 0 (Antigens, CD)
RN  - 0 (Chemokine CCL4)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Macrophage Inflammatory Proteins)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Administration, Topical
MH  - Animals
MH  - Antigens, CD/administration & dosage/*pharmacology
MH  - Chemokine CCL4
MH  - Chemokine CCL5/*genetics
MH  - Cornea/metabolism
MH  - *Corneal Transplantation
MH  - Gene Expression/*drug effects
MH  - Graft Rejection/metabolism/*prevention & control
MH  - Graft Survival/drug effects
MH  - Macrophage Inflammatory Proteins/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nuclease Protection Assays
MH  - Ophthalmic Solutions/administration & dosage/pharmacology
MH  - RNA, Messenger/*biosynthesis
MH  - Random Allocation
MH  - Receptors, Tumor Necrosis Factor/administration & dosage
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Solubility
MH  - Transplantation, Homologous
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors
EDAT- 2000/12/15 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/12/15 11:00
PHST- 2000/12/15 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/15 11:00 [entrez]
AID - els90065 [pii]
AID - 10.1001/archopht.118.12.1666 [doi]
PST - ppublish
SO  - Arch Ophthalmol. 2000 Dec;118(12):1666-71. doi: 10.1001/archopht.118.12.1666.