Assessment of selected adhesion molecule and proinflammatory cytokine levels in the vitreous body of patients with type 2 diabetes — role of the inflammatory–immune process in the pathogenesis of proliferative diabetic retinopathy

  • Joanna Adamiec-Mroczek
  • Jolanta Oficjalska-Młyńczak
Retinal Disorders

Abstract

Background

The aim of the study is to demonstrate the participation of the inflammatory-immune process in the pathogenesis of proliferative diabetic retinopathy (PDR).

Methods

Twenty four women and 22 men with type 2 diabetes (mean age 63.97 ± 9.00 years, mean duration of diabetes 12.56 ± 6.87 years) were enrolled in the study. Serum concentrations of soluble forms of ICAM-1, VCAM-1 as well as IL-6 and TNF-α were evaluated in all study subjects. In 19 patients, simultaneous assessment of selected parameter levels in both serum and vitreous samples was performed. Vitrectomy was performed due to intravitreal hemorrhage, accompanied in some patients by traction retinal detachment. The control group consisted of 15 patients having undergone vitrectomy for reasons other than PDR. Tests were performed using the ELISA method.

Results

Serum and intraocular concentrations of sICAM-1, sVCAM-1, IL-6, TNF-α were considerably higher in study subjects with PDR than in controls. Simultaneously, a positive correlation was found between intraocular sVCAM-1 (r = 0.590, p = 0.007), TNF-α (r = 0.822, p < 0.001) concentrations and HbA1c levels. The above-mentioned dependence was not shown for sICAM-1 and IL-6 vitreous concentration. Local vitreous VCAM-1 level increase was also dependent on vitreous TNF-α concentration growth (r = 0.470, p = 0.043). No significant correlation was found between serum and vitreous levels of the selected parameters in the group of 19 patients with PDR.

Conclusions

Increase in sICAM-1 and sVCAM-1 levels, as well as their correlation with high vitreous IL-6 and TNF-α concentrations in patients with PDR, seem to confirm the inflammatory–immune nature of this process. In diabetes, inadequate metabolic control remains an important risk factor in the development of PDR.

Keywords

Proliferative diabetic retinopathy Adhesion molecule IL-6 TNF-alpha, endothelium 

References

  1. 1.
    Abiko T, Abiko A, Clermont AC (2003) Characterization of retinal leukostasis and hemodynamics in insulin resistance and diabetes. Diabetes 52:829–837PubMedCrossRefGoogle Scholar
  2. 2.
    Adamis AP (2002) Is diabetic retinopathy an inflammatory disease? Br J Ophthalmol 86:363–365PubMedCrossRefGoogle Scholar
  3. 3.
    Barouch FC, Miyamoto K, Allport JR, Fujita K, Bursell SE, Aiello LP et al (2000) Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes. Invest Ophthalmol Vis Sci 41(5):1153–1158PubMedGoogle Scholar
  4. 4.
    Doganay S, Evereklioglu C, Er H, Turkoz Y, Sevinc A, Mehmet N et al (2002) Comparison of serum NO, TNF-α, IL-1β, sIl-2R, IL-6 and IL-8 levels with grades of retinopathy in patients with diabetes mellitus. Eye 16:163–170PubMedCrossRefGoogle Scholar
  5. 5.
    Hernandez C, Burgos R, Canton A, Garcia-Arumi J, Segura RM, Simo R (2001) Vitreous levels of vascular cell adhesion molecule and vascular endothelial growth factor in patients with proliferative diabetic retinopathy: a case-control study. Diabetes Care 24(3):516–521PubMedCrossRefGoogle Scholar
  6. 6.
    Matsumoto K, Sera Y, Ueki Y, Inukai G, Niiro E, Miyake S (2002) Comparison of serum concentrations of soluble adhesion molecules in diabetic microangiopathy and macroangiopathy. Diabet Med 19(10):822–826PubMedCrossRefGoogle Scholar
  7. 7.
    Olson JA, Whitelaw CM, McHardy KC, Pearson DWM, Forrester JV (2002) Soluble leucocyte adhesion molecules in diabetic retinopathy stimulate retinal capillary endothelial cell migration. Diabetologia 40:1166–1171CrossRefGoogle Scholar
  8. 8.
    Adamiec J, Oficjalska-Młyńczak J (2005) The role of cellular adhesion molecule in the development of proliferative diabetic retinopathy. Acta Ophthalmologica Polonica 107(4–6):330–333PubMedGoogle Scholar
  9. 9.
    Kao PC, Wu TJ, Ho LL, Li XJ (2000) Current trends and new approaches in the management of diabetes mellitus. Ann Clin Lab Sci 30:339–345PubMedGoogle Scholar
  10. 10.
    Meleth AD, Agrón E, Chang CC, Reed GF, Arora K, Byrnes G, Csaky KG, Ferris FL, Chew EY (2005) Serum inflammatory markers in diabetic retinopathy. Invest Ophthalmol Vis Sci 46:4295–4301PubMedCrossRefGoogle Scholar
  11. 11.
    Limb GA, Chignell AH, Green W, LeRoy F, Dumonde DC (1996) Distribution of TNF alpha and its reactive vascular adhesion molecules in fibrovascular membranes of proliferative diabetic retinopathy. Br J Ophthalmol 80(2):168–173PubMedCrossRefGoogle Scholar
  12. 12.
    Van Seventer GA, Shimizu Y, Horgan KJ, Shaws S (1990) the LFA-1 ligand ICAM-1 provides an important costimulatory signal for T-cell receptor-mediated activation of resting T cells. J Immunol 144:4579–4586PubMedGoogle Scholar
  13. 13.
    Altmann DM, Hogg N, Trowsdale J, Wilkinson D (1989) Cotransfection of ICAM-1 and HLA-DE reconstitutes human antigen-presenting cell function in mouse L cells. Nature 338:512–514PubMedCrossRefGoogle Scholar
  14. 14.
    Dougherty GJ, Murdoch S, Hogg N (1988) The function of human intercellular adhesion molecule-1 (ICAM-1) in the generation of an immune response. Eur J Immunol 18:35–39PubMedCrossRefGoogle Scholar
  15. 15.
    Cukiernik M, Hileeto D, Evans T, Mukherjee S, Downey D, Chakrabarti S (2004) Vascular endothelial growth factor in diabetes induced early retinal abnormalities. Diabetes Res Clin Pract 65(3):197–208PubMedCrossRefGoogle Scholar
  16. 16.
    Eastern and Southern European Region (2000) Recommendations for the management of patients with type 2 diabetes mellitus in the Central. Int Journ Postgraduate Train Med 8Google Scholar
  17. 17.
    Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42(6):1206–1252PubMedCrossRefGoogle Scholar
  18. 18.
    Schalkwijk CG, Chaturvedi N, Twaafhoven H, Van Hinsbergh VW, Stehouwer CD (2002) Amadori-albumin correlates with microvascular complications and precedes nephropathy in type 1 diabetic patients. Eur J Clin Invest 32:500–506PubMedCrossRefGoogle Scholar
  19. 19.
    Schram MT, Chaturvedi N, Schalkwijk C, Giorgino F, Ebeling P, Fuller JH et al (2003) Vascular risk factors and markers of endothelial function as determinants of inflammatory markers in type 1 diabetes. Diabetes Care 26:2165–2173PubMedCrossRefGoogle Scholar
  20. 20.
    Monaco C, Paleolog E (2004) Nuclear factor κB: a potential therapeutic target in atherosclerosis and thrombosis. Cardiovasc Res 61:671–682PubMedCrossRefGoogle Scholar
  21. 21.
    Schalkwijk CG, Stehouwer CDA (2005) Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin Sci 109:143–159PubMedCrossRefGoogle Scholar
  22. 22.
    American Diabetes Association (2004) Clinical practice recommendations. Diabetes Care 27(Suppl.1)Google Scholar
  23. 23.
    Bagg W, Ferri C, Desideri G, Gamble G, Ockelford P, Braatvedt GD (2001) The influences of obesity and glycemic control on endothelial activation in patients with type 2 diabetes. J Clin Endocrinol Metab 86:5491–5497PubMedCrossRefGoogle Scholar
  24. 24.
    Klein R, Klein BEK (2002) Blood pressure control and diabetic retinopathy. Br J Ophthalmol 86:365–367PubMedCrossRefGoogle Scholar
  25. 25.
    Zhang LY, Krzentowski GA, Lefebvre PJ (2001) Risk developing retinopathy in diabetes control and complications trial type 1 diabetic patients with good and poor metabolic control. Diabetes Care 23:1275–1279CrossRefGoogle Scholar
  26. 26.
    Freyberger H, Brocker M, Yakut H, Hammer J, Effert R, Schifferdecker E (2002) Increased levels of platelet-derived growth factor in vitreous fluid of patients with proliferative diabetic retinopathy. Exp Clin Endocrinol Diabetes 108:106–109CrossRefGoogle Scholar
  27. 27.
    Matz R (2000) The target for good glycemic control should be an HbA1c concentrations of less than 0.07. West J Med 173:179–180PubMedCrossRefGoogle Scholar
  28. 28.
    Őzmen B, Boyvada S (2003) The relationship between self-monitoring of blood glucose control and glycosylated haemoglobin in patients with type 2 diabetes with and without diabetic retinopathy. J Diabetes Complications 5:186–192Google Scholar
  29. 29.
    Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA et al (2000) Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35). BMJ 321:405–412PubMedCrossRefGoogle Scholar
  30. 30.
    Van Leiden HA, Dekker JJ, Moll AC, Nijpels G, Heine RJ, Bouter LM et al (2002) Blood pressure, lipids, and obesity are associated with retinopathy. Diabetes Care 25:1320–1325PubMedCrossRefGoogle Scholar
  31. 31.
    Stratton IM, Kohner EM, Aldington SJ, Turner RC, Holmann RR, Manley SE et al (2001) UKPDS 50: risk factors for incidence and progression of retinopathy in type II diabetes over 6 years from diagnosis. Diabetologia 44:156–163PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Joanna Adamiec-Mroczek
    • 1
  • Jolanta Oficjalska-Młyńczak
    • 1
  1. 1.Department of OphthalmologyWroclaw Medical UniversityWrocławPoland

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