The cornea is the thin, transparent tissue at the front of the eye through which light must pass unhindered for good vision. The cornea can be damaged by disease or injury. Each year over 1,500 corneal grafts are performed in Australia to restore vision. Contrary to popular belief, corneal grafts do fail with the main reason being immunological rejection. Corneal graft rejection is believed to be driven by T cell mediated inflammatory responses. Another potentially blinding inflammatory eye disease is Acute Anterior Uveitis (AAU). AAU causes considerable pain and is a significant cause of loss of employment for young sufferers . Antibodies against specific cell markers have shown potential in blocking the types of reactions involved in development of these two diseases. Anti-inflammatory cytokines (such as IL-10) also show potential in dampening damaging immune responses. The aim of this project is to use gene therapy to express immunomodulatory proteins in ocular tissues in order to combat inflammatory eye disease. We have demonstrated gene transfer via adenovirus-based vectors in sheep, rat, pig and human corneas. Expression is concentrated at, but not limited to, the corneal endothelium. In this laboratory, expression of ovine IL-10 by the corneal endothelium prolongs corneal graft survival in the sheep (Klebe et al., 2001). To assist the extension of this work to the clinic (where all corneal graft patients are given topical steroid post-operatively), we wish to place the expression of IL-10 under steroid-inducible control. Systemic treatment with monoclonal antibodies against the cell surface marker CD4 blocked disease development in rat models of corneal graft rejection and uveitis in this laboratory. We have constructed adenovirus-based vectors to induce the expression of anti-CD4 antibody fragments in corneal endothelium, which will be trialed in the established disease models in the rat. Future aims of this project are to transfer genes expressing reagents against other cell surface molecules, including CD28, in an effort to increase long-term corneal graft survival and/or complete blockage of experimental uveitis.