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PB Williams, NE Alvarez Chedz, T Parker, A Fateh, DA Fellner, FA Lattanzio, JD Shepard; Mitigation of Corneal Rejection Following Pretreatment With Anti-Icam Oligonucleotide . Invest. Ophthalmol. Vis. Sci. 2002;43(13):135.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Eliminating corneal rejection from corneal transplantation is a highly cost effective endeavor. ISIS 9125 is an anti-sense molecule that inhibits the expression of ICAM-1, an intracellular adhesion molecule. This study assesses the protective effect of corneal donor pretreatment with ISIS 9125. Methods: Corneal allografts (3mm), removed from anesthetized donor ACI rats, were transplanted to anesthetized Lewis rats. Recipients were randomized to no steroids, daily topical steroids, or to incubation in either OptisolTM with ISIS 9125 (400µg/ml), or OptisolTM alone for 24 hr before transplantation. Rejection criteria included cornea opacity, neovascularization, keratic precipitates and conjunctival inflammation. Confocal microscopy was used to document epithelial, stromal and endothelial changes in vivo. Corneas were harvested, after 3d or when rejection criteria were met, and examined by light microscopy (H&E) and scanning electron microscopy. Results: Corneas transplanted immediately after removal from donor rats rejected an average of 5.9 d (range 4-8 d), while those treated with topical steroids lasted an average of 8.4 d (range 6-11 d). The group, whose corneas were incubated in OptisolTM alone for 24 hr, rejected an average of 4.8 d (range 3-7 d). The group, whose corneas were incubated in ISIS 9125 for 24 hr, rejected an average of 6.3 d (range 6-10 d). By day 3, the ISIS 9125 group was graded 50% better than the OptisolTM alone group for corneal opacity and neovascularization. However, the ISIS 9125 group had more corneal edema than the OptisolTM alone group. The scaled data for the corneas harvested on post-op day 3 suggest a trend toward decreased rejection in the ISIS 9125 plus group. Confocal microscopy analysis indicates there is a significant reduction in leukocyte infiltration with use of ISIS 9125. Conclusions: Topical steroids increased days to rejection by 30%, confirming the validity of the transplant model. Incubation with ISIS 9125 increased days to rejection by 25% over OptisolTM alone. Based on these preliminary data, pretreatment of the cornea with ISIS 9125 may reduce the incidence of or delay the onset of rejection reaction, as well as decrease the inflammation associated with the rejection reaction.
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