Skip to main content

Advertisement

Log in

Role of interleukin-1β in hypoxia-induced depression of glutamate uptake in retinal Müller cells

  • Basic Science
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Background

It is suggested that hypoxic–ischemic retinal diseases induce loss of retinal ganglion cells. Excess glutamate release is involved in these conditions. A predominant function of Müller cells is to regulate glutamate levels, but in these diseases the function is compromised. The present study was performed to investigate the role of interleukin-1β(IL-1β)on the glutamate uptake in retinal Müller cells under hypoxia and to study the possible mechanism.

Methods

The levels of IL-1β,Kir4.1, and GLAST in retinal Müller cells under hypoxia were analyzed by Western blotting and realtime-RT-PCR, and glutamate uptake assay was undertaken to investigate the activity of GLAST. After being treated with IL-1βunder normoxia, these proteins (Kir4.1 and GLAST) and their mRNAs, and glutamate uptake activity in Müller cells were investigated. To confirm the effect of IL-1βon glutamate uptake activity in Müller cells, addition of IL-1ra was used.

Results

Under hypoxia, Müller cells glutamate uptake, Kir4.1 and GLAST expressions were decreased significantly; however, IL-1βexpression was increased. IL-1βtreatment induced depression of glutamate uptake, decrease of Kir4.1 and GLAST expressions in retinal Müller cells under normoxia. Moreover, addition of IL-1ra significantly ameliorated decreases in Kir4.1 and GLAST expressions, and compromise of glutamate uptake activity in retinal Müller cells under hypoxia.

Conclusions

These findings indicated that decreases in Kir4.1 and GLAST expressions and depression of glutamate uptake in retinal Müller cells under hypoxia may be induced by the inflammatory cytokine IL-1β.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Stahl A, Agostini H, Hansen LL, Feltgen N (2007) Bevacizumab in retinal vein occlusion—results of a prospective case series. Graefes Arch Clin Exp Ophthalmol 245:1429–1436

    Article  CAS  PubMed  Google Scholar 

  2. Linsenmeier RA, Braun RD, McRipley MA, Padnick LB, Ahmed J, Hatchell DL, McLeod DS, Lutty GA (1998) Retinal hypoxia in long-term diabetic cats. Invest Ophthalmol Vis Sci 39:1647–1657

    CAS  PubMed  Google Scholar 

  3. Flammer J (1994) The vascular concept of glaucoma. Surv Ophthalmol 38(Suppl):S3–S6

    Article  PubMed  Google Scholar 

  4. Tezel G, Wax MB (2004) The immune system and glaucoma. Curr Opin Ophthalmol 15:80–84

    Article  PubMed  Google Scholar 

  5. Park SW, Cho CS, Jun HO, Ryu NH, Kim JH, Yu YS, Kim JS, Kim JH (2012) Anti-angiogenic effect of luteolin on retinal neovascularization via blockade of reactive oxygen species production. Invest Ophthalmol Vis Sci 53:7718–7726

    Article  PubMed  Google Scholar 

  6. Tezel G, Yang X (2004) Caspase-independent component of retinal ganglion cell death, in vitro. Invest Ophthalmol Vis Sci 45:4049–4059

    Article  PubMed  Google Scholar 

  7. Tinjust D, Kergoat H, Lovasik JV (2002) Neuroretinal function during mild systemic hypoxia. Aviat Space Environ Med 73:1189–1194

    PubMed  Google Scholar 

  8. Neal MJ, Cunningham JR, Hutson PH, Hogg J (1994) Effects of ischaemia on neurotransmitter release from the isolated retina. J Neurochem 62:1025–1033

    Article  CAS  PubMed  Google Scholar 

  9. Ohia SE, Awe OS, Opere CA, LeDay AM, Harris LC, Sharif NA (2001) Hypoxia-induced [(3)H]D-aspartate release from isolated bovine retina: modulation by calcium-channel blockers and glutamatergic agonists and antagonists. Curr Eye Res 23:386–392

    Article  CAS  PubMed  Google Scholar 

  10. Rego AC, Santos MS, Oliveira CR (1996) Oxidative stress, hypoxia, and ischemia-like conditions increase the release of endogenous amino acids by distinct mechanisms in cultured retinal cells. J Neurochem 66:2506–2516

    Article  CAS  PubMed  Google Scholar 

  11. Tezel G, Wax MB (1999) Inhibition of caspase activity in retinal cell apoptosis induced by various stimuli in vitro. Invest Ophthalmol Vis Sci 40:2660–2667

    CAS  PubMed  Google Scholar 

  12. Li Q, Puro DG (2002) Diabetes-induced dysfunction of the glutamate transporter in retinal Müller cells. Invest ophthalmol Vis Sci 43:3109–3116

    PubMed  Google Scholar 

  13. Maragakis NJ, Rothstein JD (2001) Glutamate transporters in neurologic disease. Arch Neurol 58:365–370

    Article  CAS  PubMed  Google Scholar 

  14. Harada T, Harada C, Watanabe M, Inoue Y, Sakagawa T, Nakayama N, Sasaki S, Okuyama S, Watase K, Wada K, Tanaka K (1998) Functions of the two glutamate transporters GLAST and GLT-1 in the retina. Proc Natl Acad Sci U S A 958:4663–4666

    Article  Google Scholar 

  15. Rauen T, Taylor WR, Kuhlbrodt K, Wiessner M (1998) High-affinity glutamate transporters in the rat retina: a major role of the glial glutamate transporter GLAST-1 in transmitter clearance. Cell Tissue Res 291:19–31

    Article  CAS  PubMed  Google Scholar 

  16. Lehre KP, Davanger S, Danbolt NC (1997) Localization of the glutamate transporter protein GLAST in rat retina. Brain Res 744:129–137

    Article  CAS  PubMed  Google Scholar 

  17. Xie B, Qin Jiao Y, Cheng YZ, Shen X (2012) Effect of pigment epithelium derived factor on the glutamate uptake in retinal Müller cells under high glucose conditions. Invest Ophthal Vis Sci 53:1023–1032

    Article  CAS  PubMed  Google Scholar 

  18. Francke M, Faude F, Pannicke T, Bringmann A, Eckstein P, Reichelt W, Wiedemann P, Reichenbach A (2001) Electrophysiology of rabbit Müller (glial) cells in experimental retinal detachment and PVR. Invest Ophthalmol Vis Sci 42:1072–1079

    CAS  PubMed  Google Scholar 

  19. Napper GA, Pianta MJ, Kalloniatis M (1999) Reduced glutamate uptake by retinal glial cells under ischemic/hypoxic conditions. Vis Neurosci 16:149–158

    CAS  PubMed  Google Scholar 

  20. Rehak M, Hollborn M, Iandiev I, Pannicke T, Karl A, Wurm A, Kohen L, Reichenbach A, Wiedemann P, Bringmann A (2009) Retinal gene expression and Müller cell responses after branch retinal vein occlusion in the rat. Invest Ophthalmol Vis Sci 50:2359–2367

    Article  PubMed  Google Scholar 

  21. Zurolo E, de Groot M, Iyer A, Anink J, van Vliet EA, Heimans JJ, Reijneveld JC, Gorter JA, Aronica E (2012) Regulation of Kir4.1 expression in astrocytes and astrocytic tumors: a role for interleukin-1 β. J Neuroinflammation 9:280–297

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Li SY, Fung FK, Fu ZJ, Wong D, Chan HH, Lo AC (2012) Anti-inflammatory effects of lutein in retinal ischemic/hypoxic injury: in vivo and in vitro studies. Invest Ophthalmol Vis Sci 53:5976–5984

    Article  CAS  PubMed  Google Scholar 

  23. Paine SK, Basu A, Mondal LK, Sen A, Choudhuri S, Chowdhury IH, Saha A, Bhadhuri G, Mukherjee A, Bhattacharya B (2012) Association of vascular endothelial growth factor, transforming growth factor beta, and interferon gamma gene polymorphisms with proliferative diabetic retinopathy in patients with type 2 diabetes. Mol Vis 18:2749–2757

    CAS  PubMed  Google Scholar 

  24. Xin X, Rodrigues M, Umapathi M, Kashiwabuchi F, Ma T, Babapoor-Farrokhran S, Wang S, Hu J, Bhutto I, Welsbie DS, Duh EJ, Handa JT, Eberhart CG, Lutty G, Semenza GL, Montaner S, Sodhi A (2013) Hypoxic retinal Muller cells promote vascular permeability by HIF-1-dependent up-regulation of angiopoietin-like 4. Proc Natl Acad Sci U S A 110:E3425–E3434

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Sivakumar V, Foulds WS, Luu CD, Ling EA, Kaur C (2011) Retinal ganglion cell death is induced by microglia derived pro-inflammatory cytokines in the hypoxic neonatal retina. J Pathol 224:245–260

    Article  CAS  PubMed  Google Scholar 

  26. Hangai M, Yoshimura N, Yoshida M, Yabuuchi K, Honda Y (1995) Interleukin-1 gene expression in transient retinal ischemia in the rat. Invest Ophthalmol Vis Sci 36:571–578

    CAS  PubMed  Google Scholar 

  27. Ward MM, Jobling AI, Kalloniatis M, Fletcher EL (2005) Glutamate uptake in retinal glial cells during diabetes. Diabetologia 48:351–360

    Article  CAS  PubMed  Google Scholar 

  28. Shono NI, Baskaeva EM (1989) Bradford’s method of determining protein: application, advantages and disadvantages. Lab Delo 4:4–7

    PubMed  Google Scholar 

  29. Kusner L, Sarthy V, Mohr S (2004) Nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase: a role in high glucose-induced apoptosis in retinal Müller cells. Invest Ophthalmol Vis Sci 45:1553–1561

    PubMed  Google Scholar 

  30. Kowluru RA, Odenbach S (2004) Role of interleukin-1beta in the pathogenesis of diabetic retinopathy. Br J Ophthalmol 88:1343–1347

    Article  CAS  PubMed  Google Scholar 

  31. Vik H, Holen E, Dybendal T, Elsayed S (1989) Reestimations of the protein concentrations of birch pollen allergen extracts selected as candidates for the international standard (IS) preparation. Ann Allergy 62:87–90

    CAS  PubMed  Google Scholar 

  32. Gerhardinger C, McClure KD, Romeo G, Podestà F, Lorenzi M (2001) IGF-I mRNA and signaling in the diabetic retina. Diabetes 50:175–183

    Article  CAS  PubMed  Google Scholar 

  33. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29:e45

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Lange J, Yafai Y, Reichenbach A, Wiedemann P, Eichler W (2008) Regulation of pigment epithelium-derived factor production and release by retinal glial (Müller) cells under hypoxia. Invest Ophthalmol Vis Sci 49:5161–5167

    Article  PubMed  Google Scholar 

  35. Pannicke T, Iandiev I, Uckermann O, Biedermann B, Kutzera F, Wiedemann P, Wolburg H, Reichenbach A, Bringmann A (2004) A potassium channellinked mechanism of glial cell swelling in the postischemic retina. Mol Cell Neurosci 26:493–502

    Article  CAS  PubMed  Google Scholar 

  36. Birkle DL, Bazan NG (1989) Light exposure stimulates arachidonic acid metabolism in intact rat retina and isolated rod outer segments. Neurochem Res 14:185–190

    Article  CAS  PubMed  Google Scholar 

  37. Tilleux S, Hermans E (2008) Down-regulation of astrocytic GLAST by microglia-related inflammation is abrogated in dibutyryl cAMP-differentiated cultures. J Neurochem 105:2224–2236

    Article  CAS  PubMed  Google Scholar 

  38. Korn T, Magnus T, Jung S (2005) Autoantigen specific T cells inhibit glutamate uptake in astrocytes by decreasing expression of astrocytic glutamate transporter GLAST: a mechanism mediated by tumor necrosis factor-alpha. FASEBJ 19:1878–1880

    CAS  Google Scholar 

  39. Liu Y, Biarnés Costa M, Gerhardinger C (2012) IL-1β is upregulated in the diabetic retina and retinal vessels: cell-specific effect of high glucose and IL-1β autostimulation. PLoS One 7:e36949

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Beauregard C, Brandt PC, Chiou GC (2003) Induction of nitric oxide synthase and over-production of nitric oxide by interleukin-1b in cultured lacrimal gland acinar cells. Exp Eye Res 77:109–114

    Article  CAS  PubMed  Google Scholar 

Download references

ACKNOWLEDGMENTS

This study was supported by the National Nature Science Foundation of China (81170860), Shanghai Nature Science Foundation (11ZR1422000) and Natural Science Foundation of Ningbo City (2012A610216).

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Yisheng Zhong or Xi Shen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, C., Chen, H., Xu, C. et al. Role of interleukin-1β in hypoxia-induced depression of glutamate uptake in retinal Müller cells. Graefes Arch Clin Exp Ophthalmol 252, 51–58 (2014). https://doi.org/10.1007/s00417-013-2516-z

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-013-2516-z

Keywords

Navigation