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S. Camelo, L. Lajavardi, A. Bochot, E. Fattal, B. Thillaye-Goldenberg, M.-C. Naud, F. Behar-Cohen, Y. de Kozak; A Single Intravitreal Injection of Vasoactive Intestinal Peptide-Loaded Liposomes Reduces the Severity of Experimental Autoimmune Uveoretinitis: Effects on the Local and Systemic Immune Responses. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5214.
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© ARVO (1962-2015); The Authors (2016-present)
Local delivery of therapeutic molecules encapsulated within liposomes is a promising method to treat ocular diseases while limiting complications due to repeated intraocular injections. The purpose of the present study was to test the effect of one intravitreal injection (IVT) of Vasoactive Intestinal Peptide (VIP)-loaded liposomes on the immune response during experimental autoimmune uveoretinitis (EAU).
Twenty-four hours following IVT injection of rhodamine-labeled liposomes (Rh-Lip) in normal rats, the phenotype and distribution of cells internalizing Rh-Lip in ocular tissues and lymphoid organs was determined by immuno-fluorescence. Interactions with T cells were examined in the draining lymph nodes (LN) and the spleen. The therapeutic efficacy on EAU of a single IVT injection of Rh-Lip loaded with VIP (VIP-Rh-Lip) vs. injection of saline, VIP diluted in saline or Rh-Lip was determined 6 or 12 days after footpad immunization with S-Ag in CFA. EAU severity was assessed by clinical and histological examination and by immuno-histochemistry. Systemic immune reactivity during EAU was determined at day 20 post immunization by measuring the proliferation and cytokine secretion of cells isolated from inguinal LN draining the immunization site.
In normal rats, Rh-Lip injected IVT were detected mainly in the posterior segment of the eye, internalized by Muller cells, macrophages, and neutrophils but not microglia. In the draining cervical LN, Rh-Lip were almost exclusively internalized by resident macrophages adjacent to T lymphocytes. Whereas IVT injection of VIP-Rh-Lip 12 days after S-Ag immunization had no effect on EAU, IVT injection of VIP-Rh-Lip 6 days following S-Ag-immunization decreased EAU severity and reduced the proliferation and cytokine production of cells isolated from inguinal LN and restimulated in vitro in presence of S-Ag and ConA.
Our data show that a single IVT injection of Vip-Rh-Lip reduced EAU severity and inhibited S-Ag lymphocyte proliferation in the secondary lymphoid organs. VIP encapsulation within liposomes allowed its protection and slow release in ocular tissues and LN. IVT injection of VIP-Lip appears as an effective therapeutic startegy against EAU while avoiding the problems linked with repeated intraocular injections.
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