title: Effect of an intravitreal cyclosporine implant on experimental uveitis in horses.
abstract: The purpose of this study was to determine the effects of an intravitreal device releasing cyclosporine A (CsA) on recurrent inflammatory episodes in experimental uveitis. Nine normal horses were immunized peripherally with H37RA-mTB antigen twice, and then received 25 microg of H37RA-mTB antigen intravitreally in the right eye and an equal volume of balanced salt solution intravitreally in the left eye. Two weeks later, the animals randomly received either a CsA or a polymer implant (without CsA) in both eyes 1 week following implantation of the devices, 25 microg of H37RA-mTB antigen was reinjected into the right eye of each animal. Clinical signs of ophthalmic inflammation were graded following injections and implantation. The animals from each group were euthanized at 3, 14, and 28 days following the second injection. Aqueous and vitreous humor protein concentrations were measured. The presence, number, and type (CD4, 5 and 8) of infiltrating inflammatory cells and amount of tissue destruction were determined. Total RNA was isolated and quantitative reverse transcriptase-polymerase chain reaction was performed for equine specific interleukin (IL) 2 and 4, interferon-gamma (IFN gamma) and beta-actin. In addition, aqueous and vitreous humor and peripheral blood were collected at the termination of the experiments and analyzed for CsA concentration by HPLC. Within 4h of the first intravitreal H37RA-mTB antigen injection, each animal developed epiphora, blepharospasm, mild corneal edema, aqueous flare, myosis, and vitreous opacity. The severity of signs peaked 48 to 72 h after injection and subsequently decreased back to normal within 14 days. Following the second injection, clinical signs in the eyes with the CsA device were less severe and significantly shorter in duration than signs with the polymer only implant eyes. Aqueous and vitreous humor protein levels, infiltrating cell numbers, total number of T-lymphocytes, and levels of IL-2 and IFN gamma-mRNA were significantly less in eyes with the CsA implant compared to eyes with the polymer only. CsA implants did not completely eliminate the development of a second ('recurrent') experimental inflammatory episode in these horses. However, the duration and severity of inflammation, cellular infiltration, tissue destruction, and pro-inflammatory cytokines RNA transcript levels were significantly less in those eyes implanted with the CsA device.
authors.affiliation: Comparative Ophthalmology Research Laboratories, College of Veterinary Medicine, North Carolina State University, 27606, Raleigh, NC, USA
authors.forename: B C
authors.initials: BC
authors.lastname: Gilger
authors.forename: E
authors.initials: E
authors.lastname: Malok
authors.forename: T
authors.initials: T
authors.lastname: Stewart
authors.forename: D
authors.initials: D
authors.lastname: Horohov
authors.forename: P
authors.initials: P
authors.lastname: Ashton
authors.forename: T
authors.initials: T
authors.lastname: Smith
authors.forename: G J
authors.initials: GJ
authors.lastname: Jaffe
authors.forename: J B
authors.initials: JB
authors.lastname: Allen
mesh_terms: D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D004343:Drug Implants; D006734:Horse Diseases / Q000188:drug therapy* / Q000276:immunology; D006736:Horses; D007150:Immunohistochemistry / Q000662:veterinary; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D007376:Interleukin-2 / Q000096:biosynthesis / Q000378:metabolism; D018655:Lymphocyte Count / Q000662:veterinary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D014605:Uveitis / Q000188:drug therapy / Q000276:immunology / Q000662:veterinary*
chemical_list: D004343:Drug Implants; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D012333:RNA, Messenger; D007371:Interferon-gamma; D016572:Cyclosporine