Local release of rapamycin by microparticles delays islet rejection within the anterior chamber of the eye

The anterior chamber of the eye (ACE) has emerged as a promising clinical islettransplantation site because of its multiple advantages over the conventional intra-hepatic portal site. This includes reduced surgical invasiveness and increased isletgraft survival rate. It also allows for enhanced accessibility and monitoring of the islets. Although the ACE is initially an immuno-privileged site, this privilege is disrupted once the isletgrafts are re-vascularized. Given that the ACE is a confined space, achieving graft immune tolerancethrough local immunosuppressive drugdelivery is therefore feasible. Here, we show that isletrejection in the ACE of mice can be significantly suppressed through local delivery of rapamycin by carefully designed sustained-release microparticles. In this 30-day study, allogeneic isletgrafts with blank microparticleswere completely rejected 18 days post-transplantation into mice. Importantly, allogeneic isletgrafts co-injected with rapamycin releasing microparticlesinto a different eye of the same recipient were preserved much longer, with some grafts surviving for more than 30 days. Hence, isletallograft survival was enhanced by a localized and prolonged delivery of an immunosuppressive drug. We envisage that this procedure will relieve diabetic transplant recipients from harsh systemic immune suppression, while achieving improved glycemic control and reduced insulin dependence.