Downregulation of endotoxin-induced uveitis by intravitreal injection of vasoactive intestinal Peptide encapsulated in liposomes.

Détails

ID Serval
serval:BIB_FB0E148D8D99
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Downregulation of endotoxin-induced uveitis by intravitreal injection of vasoactive intestinal Peptide encapsulated in liposomes.
Périodique
Investigative Ophthalmology and Visual Science
Auteur(s)
Lajavardi L., Bochot A., Camelo S., Goldenberg B., Naud M.C., Behar-Cohen F., Fattal E., de Kozak Y.
ISSN
0146-0404 (Print)
ISSN-L
0146-0404
Statut éditorial
Publié
Date de publication
2007
Peer-reviewed
Oui
Volume
48
Numéro
7
Pages
3230-3238
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov'tPublication Status: ppublish
Résumé
PURPOSE: To reestablish the immunosuppressive microenvironment of the eye, disrupted by ocular inflammation during endotoxin-induced uveitis (EIU), by means of intravitreal injection of vasoactive intestinal peptide (VIP) in saline or encapsulated in liposomes, to increase its bioavailability and efficiency.
METHODS: EIU was induced in Lewis rats by subcutaneous injection of lipopolysaccharide (LPS). Simultaneously, animals were intravitreally injected with saline, saline/VIP, VIP-loaded liposomes (VIP-Lip), or unloaded liposomes. EIU severity and cellular infiltration were assessed by clinical examination and specific immunostaining. VIP concentration was determined in ocular fluids by ELISA. Ocular expression of inflammatory cytokine and chemokine mRNAs was detected by semiquantitative RT-PCR. Biodistribution of rhodamine-conjugated liposomes (Rh-Lip) was analyzed by immunohistochemistry in eyes and regional cervical lymph nodes (LNs).
RESULTS: Twenty-four hours after intravitreal injection of VIP-Lip, VIP concentration in ocular fluids was 15 times higher than after saline/VIP injection. At that time, EIU clinical severity, ocular infiltrating polymorphonuclear leukocytes (PMNs), and, to a lesser extent, ED1(+) macrophages, as well as inflammatory cytokine and chemokine mRNA expression, were significantly reduced in VIP-Lip-injected rats compared with rats injected with saline/VIP, unloaded liposomes, or saline. Rh-Lip was distributed in vitreous, ciliary body, conjunctiva, retina, and sclera. It was internalized by macrophages and PMNs, and VIP colocalized with liposomes at least up to 14 days after injection. In cervical LNs, resident macrophages internalized VIP-Rh-Lip, and some adjacent lymphocytes showed VIP expression.
CONCLUSIONS: VIP was efficient at reducing EIU only when formulated in liposomes, which enhanced its immunosuppressive effect and controlled its delivery to all tissues affected by or involved in ocular inflammation.
Mots-clé
Animals, Aqueous Humor/metabolism, Cytokines/genetics, Down-Regulation, Immunotherapy, Injections, Lipopolysaccharides, Liposomes, Lymph Nodes/metabolism, Macrophages/immunology, Male, Microscopy, Confocal, Microscopy, Fluorescence, Neutrophils/immunology, Phosphatidylethanolamines, Polyethylene Glycols, RNA, Messenger/metabolism, Rats, Rats, Inbred Lew, Reverse Transcriptase Polymerase Chain Reaction, Salmonella typhimurium, Uveitis/genetics, Uveitis/metabolism, Vasoactive Intestinal Peptide/administration & dosage, Vasoactive Intestinal Peptide/pharmacokinetics, Vitreous Body/drug effects, Vitreous Body/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/08/2013 14:44
Dernière modification de la notice
20/08/2019 16:26
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