Effect of an intravitreal cyclosporine implant on experimental uveitis in horses

The purpose of this study was to determine the effects of an intravitreal d evice releasing cyclosporine A (CsA)on recurrent inflammatory episodes in e xperimental uveitis. Nine normal horses were immunized peripherally with H3 7RA-mTB antigen twice, and then received 25 mug of H37RA-mTB antigen intrav itreally in the right eye and an equal volume of balanced salt solution int ravitreally 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 follow ing implantation of the devices, 25 mug of H37RA-mTB antigen was reinjected into the right eye of each animal. Clinical signs of ophthalmic inflammati on 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 pres ence, number, and type (CD4, 5 and 8) of infiltrating inflammatory cells an d 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 bloo d were collected at the termination of the experiments and analyzed for CsA concentration by HPLC. Within 4 h of the first intravitreal H37RA-mTB anti gen injection, each animal developed epiphora, blepharospasm, mild corneal edema, aqueous hare, myosis, and vitreous opacity. The severity of signs pe aked 48 to 72h after injection and subsequently decreased back to normal wi thin 14 days. Following the second injection, clinical signs in the eyes wi th the CsA device were less severe and significantly shorter in duration th an signs with the polymer only implant eyes. Aqueous and vitreous humor pro tein 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 c ompletely 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-inflammat ory cytokines RNA transcript levels were significantly less in those eyes i mplanted with the CsA device. (C) 2000 Elsevier Science B.V. All rights res erved.