Turkiye Klinikleri Journal of Ophthalmology

.: ORIGINAL RESEARCH
Neovasküler Yaşa Bağlı Makula Dejenerasyonlu Olgularda Serum Vasküler Endotelyal Büyüme Faktörü ve Netrin-1 Düzeyinin Değerlendirilmesi: Olgu Kontrol Çalışması
Evaluation of Serum Vascular Endothelial Growth Factor and Netrin-1 Levels in Patients with Neovascular Age-Related Macular Degeneration: Case-Control Study
Murat OKUTUCUa, Hüseyin FINDIKa, Feyzahan UZUNa, Mehmet Gökhan ASLANa, Medeni ARPAa
aRecep Tayyip Erdoğan Üniversitesi Tıp Fakültesi, Göz Hastalıkları ABD, Rize, Türkiye
Turkiye Klinikleri J Ophthalmol. 2022;31(3):119-26
doi: 10.5336/ophthal.2021-86158
Article Language: TR
Full Text
ÖZET
 Amaç: Bu çalışmanın amacı, neovasküler yaşa bağlı makula dejenerasyonu (n-YBMD) hastalarında serum vasküler endotelyal büyüme faktörü [vascular endothelial growth factor (VEGF)] ve netrin-1 düzeyini sağlıklı kontrol grubu ile karşılaştırarak, bu vasküler belirteçlerin düzeyindeki değişikliğin sistemik problemlerin belirtisi olup olmadığını araştırmaktır. Gereç ve Yöntemler: Kliniğimizde n-YBMD teşhisi almış ve intravitreal enjeksiyon planlanan 37 hasta ve kontrol grubu olarak katarakt cerrahisi planlanan 34 hasta dâhil edildi. Çalışma ve kontrol grubu hastalarında serum VEGF ve netrin-1 düzeyi enzime bağlı immünosorbent deney yöntemi kullanılarak ölçüldü. Bulgular: Çalışma grubunun medyan yaş değeri 77 (61-84) kontrol grubunun ise 75 (50-87) idi. N-YBMD grubunda serum netrin-1 ve netrin-1/VEGF oranı kontrol grubuna göre anlamlı olarak düşük ve serum VEGF oranı anlamlı olarak yüksek bulundu (tümü p<0,001). Alıcı işletim karakteristiği [receiver operating characteristic (ROC)] analizine göre netrin- 1 seviyesi n-YBMD'yi tahmin etmek için orta düzeyde bir kesinliğe sahipti. ROC eğrisi altında kalan alan %83,78 [%95 GA (güven aralığı), 68-93,8)] duyarlılık ve %85,29 (%95 GA, 68,9-95) özgüllük ile 0,883 (%95 GA, 0,797-0,970) olarak bulundu. Netrin-1 seviyeleri için en iyi kesim değeri ≤485,1 mg/mL idi ve bu istatistiksel anlamlı olarak değerlendirildi (p<0,001). Sonuç: N-YBMD hastalarında bulunan yüksek VEGF ve düşük netrin-1 serum düzeyi bu hastalığın sistemik ve inflamatuar bir hastalık olduğunu göstermektedir. Düşük serum netrin-1/VEGF oranı ise bu hastalıkta birbiri ile ilişkili anjiyogenik mediyatörlerin sistemik dengesinin bozukluğunun göstergesidir.

Anahtar Kelimeler: Makula dejenerasyonu; netrin-1; vasküler endotelyal büyüme faktörü A; inflamasyon
ABSTRACT
 Objective: To compare serum vascular endothelial growth factor (VEGF) and netrin-1 levels in patients with neovascular age-related macular degeneration (n-AMD) with a healthy control group, to investigate whether changes in the level of these vascular markers are a sign of systemic problems. Material and Methods: In our clinic, 37 patients who were diagnosed with n-AMD and were scheduled for intravitreal injection, and 34 patients who were scheduled for cataract surgery as the control group were included in the study. Serum VEGF and netrin-1 levels were measured using the enzymelinked immunosorbent assay method in the study and control group. Results: The median age of the study group was 77 (61-84) and the control group was 75 (50-87). Serum netrin-1/VEGF ratio and netrin- 1 levels were significantly lower and VEGF levels were significantly higher in n-AMD patients compared to the control group (p<0.001 for all). According to the receiver operating characteristic (ROC) analysis, the netrin-1 level had a moderate precision to predict n-AMD. The area under the ROC curve was 0.883 [95% confidence index (CI), 0.797- 0.970] with a sensitivity of 83.78% (95% CI, 68-93.8) and a specificity of 85.29% (95% CI, 68.9-95). For netrin-1 levels, the best cut-off value was ≤485.1 mg/mL, with a statistically significant difference (p<0.001). Conclusion: Low serum netrin-1 and high VEGF levels detected in patients with neovascular AMD indicate a manifestation of systemic inflammatory disease. The low serum netrin-1/VEGF ratio indicates that the systemic balance of these biomarkers is impaired in this disease.

Keywords: Macular degeneration; netrin 1; vascular endothelial growth factor A; inflammation
REFERENCES:
  1. Klein R, Wang Q, Klein BE, Moss SE, Meuer SM. The relationship of age-related maculopathy, cataract, and glaucoma to visual acuity. Invest Ophthalmol Vis Sci. 1995;36(1):182-91. [PubMed] 
  2. Mitchell P, Liew G, Gopinath B, Wong TY. Age-related macular degeneration. Lancet. 2018;392(10153):1147-59. [Crossref]  [PubMed] 
  3. Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, et al. Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology. 2001;108(4):697-704. [Crossref]  [PubMed] 
  4. Axer-Siegel R, Bourla D, Ehrlich R, Dotan G, Benjamini Y, Gavendo S, et al. Association of neovascular age-related macular degeneration and hyperhomocysteinemia. Am J Ophthalmol. 2004;137(1):84-9. [Crossref]  [PubMed] 
  5. Seddon JM, George S, Rosner B, Rifai N. Progression of age-related macular degeneration: prospective assessment of C-reactive protein, interleukin 6, and other cardiovascular biomarkers. Arch Ophthalmol. 2005;123(6):774-82. [Crossref]  [PubMed] 
  6. Cheung CM, Wong TY. Is age-related macular degeneration a manifestation of systemic disease? New prospects for early intervention and treatment. J Intern Med. 2014;276(2):140-53. [Crossref]  [PubMed] 
  7. Baltu F, Sarici AM, Yildirim O, Mergen B, Bolat E. Investigation of vascular endothelial dysfunction in the patients with age-related macular degeneration. Cutan Ocul Toxicol. 2019;38(1):29-35. [Crossref]  [PubMed] 
  8. Lin Z, Jin J, Bai W, Li J, Shan X. Netrin-1 prevents the attachment of monocytes to endothelial cells via an anti-inflammatory effect. Mol Immunol. 2018;103:166-172. [Crossref]  [PubMed] 
  9. Nishijima K, Ng YS, Zhong L, Bradley J, Schubert W, Jo N, et al. Vascular endothelial growth factor-A is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury. Am J Pathol. 2007;171(1):53-67. [Crossref]  [PubMed]  [PMC] 
  10. Saint-Geniez M, Maharaj AS, Walshe TE, Tucker BA, Sekiyama E, Kurihara T, et al. Endogenous VEGF is required for visual function: evidence for a survival role on müller cells and photoreceptors. PLoS One. 2008;3(11):e3554. [Crossref]  [PubMed]  [PMC] 
  11. Tao Y, Libondi T, Jonas JB. Long-term follow-up after multiple intravitreal bevacizumab injections for exudative age-related macular degeneration. J Ocul Pharmacol Ther. 2010;26(1):79-83. [Crossref]  [PubMed] 
  12. Tu T, Zhang C, Yan H, Luo Y, Kong R, Wen P, et al. CD146 acts as a novel receptor for netrin-1 in promoting angiogenesis and vascular development. Cell Res. 2015;25(3):275-87. [Crossref]  [PubMed]  [PMC] 
  13. Park KW, Crouse D, Lee M, Karnik SK, Sorensen LK, Murphy KJ, et al. The axonal attractant Netrin-1 is an angiogenic factor. Proc Natl Acad Sci U S A. 2004;101(46):16210-5. [Crossref]  [PubMed]  [PMC] 
  14. Lip PL, Blann AD, Hope-Ross M, Gibson JM, Lip GY. Age-related macular degeneration is associated with increased vascular endothelial growth factor, hemorheology and endothelial dysfunction. Ophthalmology. 2001;108(4):705-10. [Crossref]  [PubMed] 
  15. Lominadze D, Dean WL, Tyagi SC, Roberts AM. Mechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular disease. Acta Physiol (Oxf). 2010;198(1):1-13. [Crossref]  [PubMed]  [PMC] 
  16. Horvath B, Hegedus D, Szapary L, Marton Z, Alexy T, Koltai K, et al. Measurement of von Willebrand factor as the marker of endothelial dysfunction in vascular diseases. Exp Clin Cardiol. 2004;9(1):31-4. [PubMed]  [PMC] 
  17. Alkan FA, Cakmak G, Karis D, Sağlam ZA, Saler T, Temiz LU, et al. The evaluation of plasma viscosity and endothelial dysfunction in smoking individuals. Clin Hemorheol Microcirc. 2014;58(3):403-13. [Crossref]  [PubMed] 
  18. Toque HA, Fernandez-Flores A, Mohamed R, Caldwell RB, Ramesh G, Caldwell RW. Netrin-1 is a novel regulator of vascular endothelial function in diabetes. PLoS One. 2017;12(10):e0186734. [Crossref]  [PubMed]  [PMC] 
  19. Sharma K, Sharma NK, Singh R, Anand A. Exploring the role of VEGF in Indian Age related macular degeneration. Ann Neurosci. 2015;22(4):232-7. [Crossref]  [PubMed]  [PMC] 
  20. Tomany SC, Wang JJ, Van Leeuwen R, Klein R, Mitchell P, Vingerling JR, et al. Risk factors for incident age-related macular degeneration: pooled findings from 3 continents. Ophthalmology. 2004;111(7):1280-7. [Crossref]  [PubMed] 
  21. Wong TY, Tikellis G, Sun C, Klein R, Couper DJ, Sharrett AR. Age-related macular degeneration and risk of coronary heart disease: the Atherosclerosis Risk in Communities Study. Ophthalmology. 2007;114(1):86-91. [Crossref]  [PubMed] 
  22. Bruikman CS, Vreeken D, Hoogeveen RM, Bom MJ, Danad I, Pinto-Sietsma SJ, et al. Netrin-1 and the Grade of Atherosclerosis Are Inversely Correlated in Humans. Arterioscler Thromb Vasc Biol. 2020;40(2):462-72. [Crossref]  [PubMed] 
  23. Nussenblatt RB, Liu B, Wei L, Sen HN. The immunological basis of degenerative diseases of the eye. Int Rev Immunol. 2013;32(1):97-112. [Crossref]  [PubMed] 
  24. Lourenço FC, Galvan V, Fombonne J, Corset V, Llambi F, Müller U, et al. Netrin-1 interacts with amyloid precursor protein and regulates amyloid-beta production. Cell Death Differ. 2009;16(5):655-63. [Crossref]  [PubMed]  [PMC] 
  25. Sun L, Ju T, Wang T, Zhang L, Ding F, Zhang Y, et al. Decreased Netrin-1 and Correlated Th17/Tregs Balance Disorder in Aβ1-42 Induced Alzheimer's Disease Model Rats. Front Aging Neurosci. 2019;11:124. [Crossref]  [PubMed]  [PMC] 
  26. Tadagavadi RK, Wang W, Ramesh G. Netrin-1 regulates Th1/Th2/Th17 cytokine production and inflammation through UNC5B receptor and protects kidney against ischemia-reperfusion injury. J Immunol. 2010;185(6):3750-8. [Crossref]  [PubMed] 
  27. Mirakaj V, Gatidou D, Pötzsch C, König K, Rosenberger P. Netrin-1 signaling dampens inflammatory peritonitis. J Immunol. 2011;186(1):549-55. [Crossref]  [PubMed] 
  28. Mirakaj V, Thix CA, Laucher S, Mielke C, Morote-Garcia JC, Schmit MA, et al. Netrin-1 dampens pulmonary inflammation during acute lung injury. Am J Respir Crit Care Med. 2010;181(8):815-24. [Crossref]  [PubMed] 
  29. Lehmann JM, Riethmüller G, Johnson JP. MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc Natl Acad Sci U S A. 1989;86(24):9891-5. [Crossref]  [PubMed]  [PMC] 
  30. Wang Z, Yan X. CD146, a multi-functional molecule beyond adhesion. Cancer Lett. 2013;330(2):150-62. [Crossref]  [PubMed] 
  31. Ye Z, Zhang C, Tu T, Sun M, Liu D, Lu D, et al. Wnt5a uses CD146 as a receptor to regulate cell motility and convergent extension. Nat Commun. 2013;4:2803. [Crossref]  [PubMed] 
  32. Bu P, Gao L, Zhuang J, Feng J, Yang D, Yan X. Anti-CD146 monoclonal antibody AA98 inhibits angiogenesis via suppression of nuclear factor-kappaB activation. Mol Cancer Ther. 2006;5(11):2872-8. [Crossref]  [PubMed] 

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30.03.2014

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