Regulation Of Cytokine Signaling Pathways In The Eye

National Eye Institute

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Abstract

Several cytokines elaborated by inflammatory cells in ocular diseases (IFNg, IL-4, IL-6, IL-10) and others that are normally secreted in anterior or posterior chamber of the eye (PDGF, EGF, IGF) mediate their biological activities through activation JAK/STAT pathways. Because many of these proteins have profound effects on gene regulation, their continuos secretion in a cell may have adverse effects on cellular physiology and several pathological conditions have been attributed to dysregulation of cytokine expression. Consequently, there is significant interest in understanding regulatory mechanisms that switch-off signals transmitted by these cytokines and understanding how their biological activities can be augmented or down-regulated. A newly described family of intracellular feed-back regulators called Suppressors of cytokine signaling (SOCS) is now a focus of intense scientific interest because of its potent inhibitory effects on a broad spectrum of cytokines. Our focus in the past fiscal year was in characterizing the repertoire of SOCS proteins in ocular tissues. Although SOCS proteins are activated in several tissues in response to cytokines or growth factors signaling, we were surprised to find constitutive expression of most SOCS members (except SOCS1) in the murine lens and lens cell lines. We also found a similar pattern of SOCS expression in RPE and Mueller cells lines suggesting that SOCS proteins may play significant roles in switching-off JAK/STAT signals in the eye. Our focus in the upcoming fiscal year will be to investigate the role of SOCS proteins in a select number ocular pathological processes such as retinal degenerative processes and uveitis.