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Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion

  • Clinical Investigation
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Abstract

Background

To investigate whether vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contributes to the pathogenesis of macular edema in eyes with branch retinal vein occlusion (BRVO), the correlations between these factors were investigated.

Methods

We studied 25 patients suffering from macular edema with BRVO and 14 patients with nonischemic ocular disease (control group). The degree of retinal ischemia was evaluated in terms of the area of capillary nonperfusion using Scion Images, and the severity of macular edema was examined using optical coherence tomography. Vitreous fluid samples were obtained at the time of vitreoretinal surgery, and VEGF and IL-6 levels in the vitreous fluid and plasma were determined by means of enzyme-linked immunosorbent assays.

Results

Vitreous fluid levels of VEGF and IL-6 were significantly elevated in patients with BRVO compared with control patients (P=0.0011 and P<0.0001, respectively). Also, the vitreous level of VEGF was significantly correlated with that of IL-6 (P=0.0012), and vitreous levels of VEGF and IL-6 were correlated with the size of the BRVO nonperfusion area (P<0.0001 and P=0.0033, respectively). Furthermore, vitreous levels of VEGF and IL-6 were correlated with the severity of macular edema (P=0.0008 and P=0.0191, respectively) and the severity of macular edema of BRVO was significantly correlated with the size of the BRVO nonperfusion area (P=0.0044).

Conclusions

The levels of VEGF and IL-6 are increased in patients with macular edema with BRVO and are significantly correlated with the size of the nonperfusion area and the severity of macular edema. Therefore, they may play a role in macular edema with BRVO.

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References

  1. Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE et al (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487

    Article  PubMed  CAS  Google Scholar 

  2. Aiello LP, Northrup JM, Keyt BA, Takagi H, Iwamoto MA (1995) Hypoxic regulation of vascular endothelial growth factor in retinal cells. Arch Ophthalmol 113:1538–1544

    PubMed  CAS  Google Scholar 

  3. Ali MH, Schlidt SA, Chandel NS, Hynes KL, Schumacker PT, Gewertz BL (1999) Endothelial permeability and IL-6 production during hypoxia: role of ROS in signal transduction. Am J Physiol 277:L1057–L1065

    PubMed  CAS  Google Scholar 

  4. Arnarsson A, Stefansson E (2000) Laser treatment and the mechanism of edema reduction in branch retinal vein occlusion. Investig Ophthalmol Vis Sci 41:877–879

    CAS  Google Scholar 

  5. Battaglia PM, Saviano S, Ravalico G (1999) Grid laser treatment in macular branch retinal vein occlusion. Graefe Arch Clin Exp Ophthalmol 237:1024–1027

    Article  Google Scholar 

  6. Campochiaro PA (2004) Reduction of diabetic macular edema by oral administration of the kinase inhibitor PKC412. Investig Ophthalmol Vis Sci 45:922–931

    Article  Google Scholar 

  7. Chahal PS, Fallon TJ, Kohner EM (1986) Measurement of blood–retinal barrier function in central retinal vein occlusion. Arch Ophthalmol 104:554–557

    PubMed  CAS  Google Scholar 

  8. Cohen T, Nahari D, Cerem LW, Neufeld G, Levi BZ (1996) Interleukin 6 induces the expression of vascular endothelial growth factor. J Biol Chem 271:736–741

    Article  PubMed  CAS  Google Scholar 

  9. Desai TR, Leeper NJ, Hynes KL, Gewertz BL (2002) Interleukin-6 causes endothelial barrier dysfunction via the protein kinase C pathway. J Surg Res 104:118–123

    Article  PubMed  CAS  Google Scholar 

  10. Funatsu H, Yamashita H, Ikeda T, Mimura T, Eguchi S, Hori S (2003) Vitreous levels of interleukin-6 and vascular endothelial growth factor are related to diabetic macular edema. Ophthalmology 110:1690–1696

    Article  PubMed  Google Scholar 

  11. Funatsu H, Yamashita H, Noma H, Mimura T, Yamashita T, Hori S (2002) Increased levels of vascular endothelial growth factor and interleukin-6 in the aqueous humor of diabetics with macular edema. Am J Ophthalmol 133:70–77

    Article  PubMed  CAS  Google Scholar 

  12. Gardner TW, Antonetti DA, Barber AJ, Lieth E, Tarbell JA (1999) The molecular structure and function of the inner blood–retinal barrier. Penn State Retina Research Group. Doc Ophthalmol 97:229–237

    Article  PubMed  CAS  Google Scholar 

  13. Gutman FA, Zegarra H (1974) The natural course of temporal retinal branch vein occlusion. Trans Am Acad Ophthalmol Otolaryngol 78:178–192

    Google Scholar 

  14. Joussen AM, Poulaki V, Qin W, Kirchhof B, Mitsiades N, Wiegand SJ, Rudge J, Yancopoulos GD, Adamis AP (2002) Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo. Am J Pathol 160:501–509

    PubMed  CAS  Google Scholar 

  15. Lutty GA, McLeod DS, Merges C, Diggs A, Plouet J (1996) Localization of vascular endothelial growth factor in human retina and choroids. Arch Ophthalmol 114:971–977

    PubMed  CAS  Google Scholar 

  16. Maruo N, Morita I, Shirao M, Murota S (1992) IL-6 increases endothelial permeability in vitro. Endocrinology 131:710–714

    Article  PubMed  CAS  Google Scholar 

  17. Michels RG, Gass JD (1974) The natural course of retinal branch vein obstruction. Trans Am Acad Ophthalmol Otolaryngol 78:166–177

    Google Scholar 

  18. Miyamoto K, Khosrof S, Bursell SE, Moromizato Y, Aiello LP, Ogura Y, Adamis AP (2000) Vascular endothelial growth factor (VEGF)-induced retinal vascular permeability is mediated by intercellular adhesion molecule-1 (ICAM-1). Am J Pathol 156:1733–1739

    PubMed  CAS  Google Scholar 

  19. Otani T, Kishi S (2000) Tomographic assessment of vitreous surgery for diabetic macular edema. Am J Ophthalmol 129:487–494

    Article  PubMed  CAS  Google Scholar 

  20. Pearlstein DP, Ali MH, Mungai PT, Hynes KL, Gewertz BL, Schumacker PT (2002) Role of mitochondrial oxidant generation in endothelial cell responses to hypoxia. Arterioscler Thromb Vasc Biol 22:566–573

    Article  PubMed  CAS  Google Scholar 

  21. Pe’er J, Folberg R, Itin A, Gnessin H, Hemo I, Keshet E (1998) Vascular endothelial growth factor upregulation in human central retinal vein occlusion. Ophthalmology 105:412–416

    Article  PubMed  CAS  Google Scholar 

  22. Planck SR, Dang TT, Graves D, Tara D, Ansel JC, Rosenbaum JT (1992) Retinal pigment epithelial cells secrete interleukin-6 in response to interleukin-1. Investig Ophthalmol Vis Sci 33:78–82

    CAS  Google Scholar 

  23. Saika S, Tanaka T, Miyamoto T, Ohnishi Y (2001) Surgical posterior vitreous detachment combined with gas/air tamponade for treating macular edema associated with branch retinal vein occlusion: retinal tomography and visual outcome. Graefe Arch Clin Exp Ophthalmol 239:729–732

    Article  CAS  Google Scholar 

  24. Senger DR, Galli SJ, Dvorak AM, Perruzzi CA, Harvey VS, Dvorak HF (1983) Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science 219:983–985

    Article  PubMed  CAS  Google Scholar 

  25. Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845

    Article  PubMed  CAS  Google Scholar 

  26. Silva RM, Faria de Abreu JR, Cunha-Vaz JG (1995) Blood–retina barrier in acute retinal branch vein occlusion. Graefe Arch Clin Exp Ophthalmol 233:721–726

    Article  CAS  Google Scholar 

  27. Tolentino MJ, Miller JW, Gragoudas ES, Jakobiec FA, Flynn E, Chatzistefanou K, Ferrara N, Adamis AP (1996) Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology 103:1820–1828

    PubMed  CAS  Google Scholar 

  28. Vinores SA, Derevjanik NL, Ozaki H, Okamoto N, Campochiaro PA (1999) Cellular mechanisms of blood–retinal barrier dysfunction in macular edema. Doc Ophthalmol 97:217–228

    Article  PubMed  CAS  Google Scholar 

  29. Yan SF, Tritto I, Pinsky D, Liao H, Huang J, Fuller G, Brett J, May L, Stern D (1995) Induction of interleukin 6 (IL-6) by hypoxia in vascular cells. Central role of the binding site for nuclear factor-IL-6. J Biol Chem 270:11463–11471

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Drs. Makiko Yamasaki, Koji Jian, Masaki Imada, Tomoko Yokoyama and Eiichirou Sugimoto for their assistance in collecting the vitreous and plasma samples and in performing the ophthalmological examinations. We also thank Katsunori Shimada of the Department of Biostatistics, STATZ Corporation, Tokyo, for assistance with the statistical analysis.

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Correspondence to Hiromu K. Mishima.

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Noma, H., Minamoto, A., Funatsu, H. et al. Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion. Graefe's Arch Clin Exp Ophthalmo 244, 309–315 (2006). https://doi.org/10.1007/s00417-004-1087-4

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  • DOI: https://doi.org/10.1007/s00417-004-1087-4

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