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C. Yu, Y. Guo, R.M. Mahdi, S. Ebong, R.M. Darrow, D.T. Organisciak, C.E. Egwuagu; SOCS Proteins Have Neuroprotective Role in the Mammalian Retina . Invest. Ophthalmol. Vis. Sci. 2003;44(13):5245.
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© ARVO (1962-2015); The Authors (2016-present)
Purposes: Many cells of the vertebrate retina that play critical roles in vision are terminally differentiated. Cumulative insults resulting from environmental stress or exposure to cytotoxic chemicals can lead to permanent loss of these cells and severe visual impairment. Although cytokines such as IFNg and IL-4 that are produced during intra-ocular inflammation are essential to host immunity, they are cytotoxic and mechanisms by which retinal cells are protected from their cytotoxic effects is not well understood. Suppressors of cytokine signaling (SOCS) are newly described negative feedback regulators of cytokine activities. In this study, we have investigated the potential role of SOCS proteins in the protection of retinal cells from toxic effects of pro-inflammatory cytokines and high intensity light.Methods: Human RPE or Muller cell line was stimulated with IFNg or IL-4 for 30 or 60 min. Activation of the requisite cytokine signaling pathways was characterized and verified by electrophoretic mobility shift assay (EMSA) and by immunoblotting using anti-phosphotyrosine Abs. RNA was isolated from retina of rats exposed to various intensities of light. Analysis and quantitation of SOCS gene expression was by RNAse protection assay (RPA), Western blotting and real-time PCR.Results: We found that SOCS5, SOCS6, SOCS7 are constitutively expressed in both cell types while SOCS1, SOCS3 and CIS are differentially induced by IL-4 or IFNg in RPE or Muller cells. In addition, we found significant induction of SOCS3 expression in the rat retina following exposure to high intensity light.Conclusion: We provide evidence that SOCS proteins are constitutively expressed in retinal cell lines and mammalian retina. These results are remarkable because SOCS proteins generally have a short half-life and are not constitutively expressed in many tissues. We also show that retinal cells respond to exposure to cytotoxic cytokines or mitigate the injurious effects of high intensity light by upregulating SOCS expression. Thus, SOCS proteins may have a neuroprotective role in the mammalian retina.
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