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NA Afshari, CB T McMullen, JE Moore, IL Campbell, T Usui, Z Haskova, B Kasander, AP Adamis; Corneal Gene Therapy with IL-1 RA Inhibits Corneal Neovascularisation & Suppresses Rejection in Penetrating Keratoplasty . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2271.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: The purpose of this study was to modulate the inflammatory environment associated with penetrating keratoplasty via gene therapy with the anti-inflammatory cytokine IL-1 RA in an attempt to alter graft survival and reduce vascularization. Methods: In a mouse model, donor corneas were transfected with IL-1 RA by injection of naked plasmid vector pIRES-EGFP-IL-1 RA 24 hours prior to penetrating keratoplasty. Corneas transfected with pIRES-EGFP (green fluorescent protein) plasmid served as controls. Statement of corneal IL-1 RA following transfection with pIRES-EGFP-IL-1 RA was assessed at 24 hours post transfection using real time PCR and Western blotting. Graft survival and graft vascularization was monitored for 56 days post engraftment. In addition, corneal VEGF protein statement was measured using ELISA at 2.5 days post engraftment with and without IL-1 RA transfection. Results: Naked gene transfer of IL-1 RA to corneal buttons 24 hours prior to their use in penetrating keratoplasty resulted in a statistically significant increase in graft survival (Kaplan Meier Survival curve, p<0.05 n=15 mice) and a decrease in graft vascularization. 2.5 days post penetrating keratoplasty corneal VEGF protein expression increased (control vs. penetrating keratoplasty, 9.9 pg/ml vs. 110 pg/ml n=4 mice p<0.05). In corneas where the button was transfected with IL-1 RA prior to transplantation a statistically significant reduction was noted in the amount of VEGF protein expressed in corneas 2.5 days post penetrating keratoplasty (IL-1 RA transfected vs. control GFP transfected, 78 pg/ml vs. 110 pg/ml, n=5 mice p=0.012). Conclusion: Transfection of a corneal donor button with IL-1 RA prior to penetrating keratoplasty produced a significant alteration in the cytokine profile which suppressed corneal neovascularization and also enhanced graft survival. VEGF levels were increased post keratoplasty but corneal transfection with IL-1RA suppressed this increase. These findings demonstrate the feasibility of using transient cytokine gene statement, either in donor or recipient corneal tissue, to beneficially alter the interaction between grafted tissue and host.
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