Novel bio-signature for the topical administration of a suppressor of cytokine signaling-1 mimetic to the equine eye: implications in treatment of Recurrent Uveitis (RU)

Abstract

Abstract Recurrent uveitis (RU) is a leading cause of ocular decrement in both humans and horses, which can lead to blindness. Equine recurrent uveitis (ERU) serves as the only spontaneous model for human RU as the eye destruction in both diseases is guided by a dysregulated cytokine milieu mediated by T lymphocytes. We have recently shown that the topical administration of a peptide (SOCS1-KIR), which mimics a natural regulator of cytokine signaling, was correlated with a reduction in clinical pathology when applied to the eye of horses with ERU. This administration was without any observed toxicity. The purpose of this study is to establish the intraocular presence of topical SOCS1-KIR treatment. As such, we administered SOCS1-KIR to the eye of experimental horses (lacking ocular pathology) to evaluate peptide localization and detection of a biological signature. SOCS1-KIR peptide, that was intravitreally-injected, was readily detectable within the retina by immunofluorescence. Although we were unable to detect topically administered SOCS1-KIR by immunofluorescence, topical administration reduced levels of TNFa and IL-10 in the aqueous humor of treated eyes. Additionally, we found that SOCS1-KIR modulated TNFa, IL-6, IL-10, RANTES, and IL-8 levels within activated healthy equine PBMC. Together these results suggest a novel biological signature that is mediated by topical SOCS1-KIR administration to the equine eye that has implications for translation to the clinical setting. This work was supported by the Grayson Jockey Club grant