Vasoactive intestinal peptide loaded in liposomes: a new immunomodulatory agent for the local treatment of experimental autoimmune uveoretinitis (EAU)

Abstract

Abstract Purpose: Local delivery of therapeutic molecules is a promising method to treat ocular diseases, while at the same time, reducing severe systemic side effects. We tested the efficacy of one intravitreal injection (IVT) of rhodamine‐labeled liposomes loaded with Vasoactive Intestinal Peptide (VIP‐Rh‐Lip) to reduce experimental autoimmune uveoretinitis (EAU). Methods: Injection of VIP‐Rh‐Lip was performed simultaneously with or 6 or 12 days after immunization with S‐Ag in CFA. Therapeutic efficacy on EAU was determined by clinical slit lamp examination. Retinal tissue destruction was assessed by histological examination, inflammatory cells infiltration by immuno‐histochemistry. Intraocular cytokine production was determined by multiplex ELISA. The proliferation and cytokine secretion by cells isolated from inguinal LN were measured. Results: IVT injection of VIP‐Rh‐Lip simultaneously and 6 days after S‐Ag immunization decreased EAU clinical score and protected retinal tissue from destruction compared to control animals. In treated rats intraocular inflammatory cytokines and NO production by intraocular macrophages was decreased suggesting they were deactivated. In vivo and in vitro T cell reactivity to S‐Ag was reduced. IL‐10 production by cells isolated from inguinal LN, re‐stimulated in vitro in presence of S‐Ag was increased in VIP‐Rh‐Lip injected rats compared to control animals. Conclusions: A single intraocular injection of VIP‐Rh‐Lip is an effective therapeutic strategy to protect ocular tissues during uveitis, by reducing intraocular inflammation and by diminishing T cell reactivity at the systemic level.