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Time-dependent expression of PEDF and VEGF in blood serum and retina of rats with oxygen-induced retinopathy

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Summary

The effects of the balance changes of pigment epithelium growth factor (PEDF) and vascular endothelial growth factor (VEGF) in whole-body and retinal tissue on rats with oxygen-induced retinopathy were investigated. Forty-eight neonatal SD rats at the age of 7 days were randomly divided into 4 groups. The neonatal rats in experimental groups were exposed to 75% to 80% oxygen for 5 days and then to normal air, and those in control groups were kept feeding in normal air. At the age of 17 and 22 days, all the neonatal rats received retina angiography with FITC-dextran and the pathological changes of retinal vessels and perfusion were observed. HE staining of the tissue section and the number counting of endothelial cells extending beyond the inner limiting membrane were performed to evaluate the endothelial proliferation. Immunohistochemistry was applied to detect the expression of PEDF and VEGF in retinal tissue, and ELISA to detect their expression in serum. A hypoxic-ischemic proliferation of retina and more endothelial cells extending beyond the inner limiting membrane were found in the neonatal rats in both experimental groups of 17-day old and 22-day old as compared with those in control group with the difference being statistically significant (P<0.01). VEGF staining of the rats in the 17-day old experimental group was significantly stronger, with an increasing positive rate, than that of the rats in the 17-day old control group (P<0.01). PEDF staining of the rats of 22 days old was weaker than that of the rats of 17 days old in the experimental groups (P<0.01). There was no significant difference in serum VEGF concentration among all groups (P>0.05). The serum PEDF concentration in the rats of 17 days old in experimental group was decreased significantly as compared with that in the rats of 17 days old in control group (P<0.01), and in experimental groups, the serum PEDF concentration of the rats of 22 days old was increased as compared with that of the rats of 17 days old (P<0.01). In conclusion, the obviously decreased serum PEDF concentration and the abnormal enhanced expression of VEGF density in local retinal tissue broke down the balance of PEDF/VEGF in whole-body or local tissues, which might play an important role in retinal vascular proliferation.

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References

  1. Thumann G. Prospectives for gene therapy of retinal degenerations. Curr Genomics, 2012,13(5):350–362

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Bhadada SV, Goyal BR, Patel MM. Angiogenic targets for potential disorders. Fundam Clin Pharmacol, 2011,25(1):29–47

    Article  CAS  PubMed  Google Scholar 

  3. Praidou A, Androudi S, Brazitikos P. Angiogenic growth factors and their inhibitors in diabetic retinopathy. Curr Diabetes Rev, 2012,6(5):304–312

    Article  Google Scholar 

  4. Smith LE, Wesolowski E, McLellan A, et al. Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci, 1994,35(1):101–111

    CAS  PubMed  Google Scholar 

  5. Lei CT, Zhang XQ, Fan YC, et al. Expression of TGF-β1 and Smad4 oxygen-induced retinopathy in neonatal mice. Yan Ke Yan Jiu (Chinese), 2006,24(5):523–525

    CAS  Google Scholar 

  6. Pan JR, Wang C, Yu QL, et al. Effect of Methyl-CpG binding domain protein 2 (MBD2) on AMD-like lesions in ApoE-deficient mice. J Huazhong Univ Sci Technolog Med Sci, 2014,34(3):408–414

    Article  CAS  PubMed  Google Scholar 

  7. Tombran TJ. PEDF in angiogenic eye diseases. Curr Mol Med, 2010,10(3):267–268

    Article  Google Scholar 

  8. Haurigot V, Villacampa P, Ribera A, et al. Long-term retinal PEDF overexpression prevents neovascularization in a murine adult model of retinopathy. PLoS One, 2012,7(7):e41511

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Zhang MX, Zhang JJ, Yan M. Inhibitory effects of endostatin on oxygen-induced retinal neovascularization in rats with retinopathy. Chin J Ocul Fundus Dis, 2005,21(5):314–317

    CAS  Google Scholar 

  10. Bai YJ, Huang LZ, Zhou AY, et al. Antiangiogenesis effects of endostatin in retinal neovascularization. J Ocul Pharmacol Ther, 2013,29(7):619–626

    Article  CAS  PubMed  Google Scholar 

  11. Dvorak HF. VPF/VEGF and the angiogenic response. Semin Perinatol, 2000,24(1):75–78

    Article  CAS  PubMed  Google Scholar 

  12. Shweiki D, Itin A, Soffer D, et al. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis, Nature, 1992,359(6398):843–845

    Article  CAS  PubMed  Google Scholar 

  13. Hartmann JS, Thompson H, Wang H, et al. Expression of vascular endothelial growth factor and pigment epithelial-derived factor in a rat model of retinopathy of prematurity. Mol Vis, 2011,17:1577–1587

    PubMed Central  CAS  PubMed  Google Scholar 

  14. Shinoda K, Ishida S, Kawashima S, et al. Comparison of the levels of hepatocyte growth factor and vascular endothelial growth factor in aqueous fluid and serum with grades of retinopathy in patients with diabetes mellitus. Br J Ophthalmol, 1999,83(7):834–837

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Sydorova M, Lee MS. Vascular endothelial growth factor levels in vitreous and serum of patients with either proliferative diabetic retinopathy or proliferative vitreoretinopathy. Ophthalmic Res, 2005,37(4):188–190

    Article  CAS  PubMed  Google Scholar 

  16. Gettins PG, Simonovic M, Volz K. Pigment epithelium-derived factor (PEDF), a serpin with potent anti-angiogenic and neurite out growth-promoting properties. Biol Chem, 2002,383(11):1677–1682

    Article  CAS  PubMed  Google Scholar 

  17. Ogata N, Wada M, Otsuji T. Expression of pigment epithelium-derived factor in normal adult rat eye and experimental choroidal neovascularization. Invest Ophthamlol Vis Sci, 2002,43(4):1168–1175

    Google Scholar 

  18. Duh EJ, Yang HS, Suzuma I, et al. Pigment epithelium-derived factor suppresses ischemia induced retinal neovascularization and VEGF-induced migration and growth. Invest Ophthalmol Vis Sci, 2002,43(3):821–829

    PubMed  Google Scholar 

  19. Volpert OV, Zaichuk T, Zhou W, et al. Induce-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor, Nat Med, 2002,8(4):349–357

    Article  CAS  PubMed  Google Scholar 

  20. Huber M, Wachtlin J. Vitreous levels of proteins implicated in angiogenesis are modulated in patients with retinal or choroidal neovascularization. Ophthalmologica, 2012,228(3):188–193

    Article  CAS  PubMed  Google Scholar 

  21. Mohan N, Monickaraj F, Balasubramanyam M, et al. Imbalanced levels of angiogenic and angiostatic factors in vitreous, plasma and postmortem retinal tissue of patients with proliferative diabetic retinopathy. J Diabetes Complications, 2012,26(5):435–441

    Article  PubMed  Google Scholar 

  22. Holekamp NM, Bouck N, Volpert O. Pigment epithelium-derived factor is deficient in the vitreous of patient with choroidal neovasculariza tion due to age-related macular degeneration. Am J Ophthalmol, 2002,134(1):22–27

    Google Scholar 

  23. Connor KM, Krah NM, Dennison RJ, et al. Quantification of oxygen-induced retinopathy in the mouse: a model of vessel loss, vessel regrowth and pathological angiogenesis. Nat Protoco, 2009,4(11):1565–1573

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Ophthalmology, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital, School of Clinical Medicine, University of Electronic Science and Technology of China, Chengdu, 610072, China

    Chun-tao Lei  (雷春涛), Jie Peng  (彭 洁), Li-feng Qiao  (乔利锋), Ying-chuan Fan  (樊映川) & Jian-bin Hu  (胡建斌)

  2. Department of Digestion, Chengdu Military General Hospital, Chengdu, 610083, China

    Xiao-Ling Wu  (吴晓玲)

  3. Kangqiao Eye Hospital of Chengdu, Chengdu, 610041, China

    Xiao-feng Chen  (陈小凤)

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  1. Chun-tao Lei  (雷春涛)
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  2. Xiao-Ling Wu  (吴晓玲)
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  3. Jie Peng  (彭 洁)
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  4. Xiao-feng Chen  (陈小凤)
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  5. Li-feng Qiao  (乔利锋)
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  6. Ying-chuan Fan  (樊映川)
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  7. Jian-bin Hu  (胡建斌)
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Correspondence to Jie Peng  (彭 洁).

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Lei, Ct., Wu, XL., Peng, J. et al. Time-dependent expression of PEDF and VEGF in blood serum and retina of rats with oxygen-induced retinopathy. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 35, 135–139 (2015). https://doi.org/10.1007/s11596-015-1402-9

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  • DOI: https://doi.org/10.1007/s11596-015-1402-9

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