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Ying Qian, MD, PhD; Iva Dekaris, MD, PhD; Satoru Yamagami, MD, PhD; M. Reza Dana, MD, MPH

Arch Ophthalmol. 2000;118:1666-1671.

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-1 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-1) 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.

From Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Mass.

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