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Karen Eastlake, Philip James Banerjee, Angshumonik Angbohang, Silke Becker, David G Charteris, Peng Tee Khaw, G Astrid Limb; Müller glia-derived cytokines are predominantly increased in the gliotic human retina. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):414.
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© ARVO (1962-2015); The Authors (2016-present)
Although it is well documented that cytokines and growth factors play a key role in retinal gliosis, the effects of these molecules on the potential modulation of retinal neurogenesis by resident human Müller stem cells (hMSC) has not yet been addressed. In order to examine the role of cytokines on the promotion or inhibition of hMSC proliferation and neural differentiation within the retina, is important to investigate whether the pattern of cytokine expression by Müller glia mimics that of the gliotic retina. We therefore compared the cytokine profile of normal and gliotic retina with that of Müller cells in culture.
Normal cadaveric retina was obtained from Moorfields Eye Bank. Retinectomy specimens were obtained upon written consent from patients undergoing retinal surgery at Moorfields Eye Hospital according to guidelines from the Local Ethics Committee. Protein lysates from tissue and MIO-M1 Müller glial cells were examined for cytokine expression using a proteome profiler antibody array (R&D Systems, UK). Quantification analysis was also conducted using a multiplex immunoassay for 27 different cytokines(BioPlex-Pro, BioRad, UK).
Qualitative cytokine arrays of gliotic retinae showed that 24 cytokines exhibited >100% increase, whilst 31 showed 50-100% increase as compared with the normal retina. In addition, out of 102 factors detected in the gliotic retina, 76 were also detected in the Müller cell lysate. Quantitative cytokine arrays revealed a significant increase in the levels of 19 cytokines in the gliotic retina compared to the normal retina. Interestingly, cytokines predominantly produced by Müller glia were found to be highly upregulated in the gliotic retina as compared with the normal retina. These included eotaxin, GCSF, MCP-1, PDGF-bb, RANTES, TNFα, VEGF and TGFβ2 (P<0.05 to P<0.001).
This study has identified a significant upregulation of a wide spectrum of inflammatory and regulatory cytokines in the gliotic retina which are predominantly expressed by Müller glia. Interestingly, the pattern of cytokine expression by Müller glia mimics that of cytokines found to be highly upregulated during gliosis, suggesting that Müller glia may be the principal source of these cytokines. We expect that results from this study will lead to investigations of the effects of selective cytokines on the inhibition of the regenerative ability of Müller glia in the human retina.
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