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CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy

  • Authors:
    • Yu Di
    • Yiou Zhang
    • Qingzhu Nie
    • Xiaolong Chen
  • View Affiliations / Copyright

    Affiliations: Department of Ophthalmology, Shengjing Affiliated Hospital, China Medical University, Shenyang, Liaoning 110004, P.R. China, Graduate School, China Medical University, Shenyang, Liaoning 110122, P.R. China
    Copyright: © Di et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1507-1518
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    Published online on: October 12, 2015
       https://doi.org/10.3892/ijmm.2015.2371
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Abstract

Retinal neovascularization (RNV) is a characteristic pathological finding of retinopathy of prematurity (ROP). Cysteine-rich 61 [Cyr61, also known as CCN family member 1 (CCN1)] has been reported to mediate angiogenesis. The aim of the present study was to investigate the mechanisms of CCN1/Cyr61-phosphoinositide 3-kinase (PI3K)/AKT signaling in ROP. The contribution of CCN1 to human umbilical vein endothelial cell (HUVEC) proliferation and apoptosis under hypoxic conditions was determined using a cell counting kit‑8 (CCK-8) and Annexin V/propidium iodide (PI) staining, respectively, as well as using siRNA targeting CCN1 (CCN1 siRNA). The cells exposed to hypoxia were also treated with the PI3K/AKT inhibitor, LY294002. In addition, mouse pups with oxygen-induced retinopathy (OIR) were administered an intravitreal injection of CCN1 siRNA. RNV was assessed by magnesium-activated adenosine diphosphate-ase (ADPase) staining. RT-qPCR, western blot analysis, immunofluorescence staining and immunohistochemistry were used to detect the distribution and expression of CCN1, PI3K and AKT. Exposure to hypoxia increased the neovascularization clock hour scores (from 1.23±0.49 to 5.60±0.73, P<0.05) and the number of preretinal neovascular cells, as well as the mRNA and protein expression levels of CCN1, PI3K and AKT (all P<0.05). The injection of CCN1 siRNA decreased the neovascularization clock hour scores and the number of preretinal neovascular cells (1.53±0.72 vs. 4.76±1.04; 12.0±2.8 vs. 31.4±2.6, respectively, both P<0.05), as well as the mRNA and protein expression levels of CCN1, PI3K and AKT (protein, -45.3, -22.5 and -28.4%; mRNA, -43.7, -58.7 and -42.9%, respectively, all P<0.05) compared to the administration of scrambled siRNA under hypoxic conditions. Treatment with LY294002 decreased the mRNA and protein expression levels of CCN1 in the cells exposed to hypoxia (both P<0.05). The administration of CCN1 siRNA resulted in less severe neovascularization in the eyes of the the mouse pups with OIR. Thus, out data suggest that CCN1 plays an important role in RNV in ROP, and may thus be a potential target for the prevention and treatment of ROP.
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View References

1 

Li Z, He T, Du K, Xing YQ, Yan Y, Chen Z, Zhang H and Shen Y: Overexpression of 15-lipoxygenase-1 in oxygen-induced ischemic retinopathy inhibits retinal neovascularization via downregulation of vascular endothelial growth factor-A expression. Mol Vis. 18:2847–2859. 2012.PubMed/NCBI

2 

Nowak-Sliwinska P, Storto M, Cataudella T, Ballini JP, Gatz R, Giorgio M, van den Bergh H, Plyte S and Wagnières G: Angiogenesis inhibition by the maleimide-based small molecule GNX-686. Microvasc Res. 83:105–110. 2012. View Article : Google Scholar

3 

Gergely K and Gerinec A: Retinopathy of prematurity - epidemics, incidence, prevalence, blindness. Bratisl Lek Listy. 111:514–517. 2010.

4 

Wang F, Bai Y, Yu W, Han N, Huang L, Zhao M, Zhou A, Zhao M and Li X: Anti-angiogenic effect of KH902 on retinal neovascularization. Graefes Arch Clin Exp Ophthalmol. 251:2131–2139. 2013. View Article : Google Scholar : PubMed/NCBI

5 

Hartnett ME and Penn JS: Mechanisms and management of retinopathy of prematurity. N Engl J Med. 367:2515–2526. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Phelps DL: Retinopathy of prematurity. Pediatr Rev. 16:50–56. 1995. View Article : Google Scholar : PubMed/NCBI

7 

No authors listed. Cryotherapy for Retinopathy of Prematurity Cooperative Group: Multicenter trial of cryotherapy for retinopathy of prematurity. 3 1/2-year outcome - structure and function. Arch Ophthalmol. 111:339–344. 1993. View Article : Google Scholar

8 

Xia XB, Xiong SQ, Song WT, Luo J, Wang YK and Zhou RR: Inhibition of retinal neovascularization by siRNA targeting VEGF(165). Mol Vis. 14:1965–1973. 2008.PubMed/NCBI

9 

Yan Y, He T, Shen Y, Chen X, Diao B, Li Z, Liu Q and Xing YQ: Adenoviral 15-lipoxygenase-1 gene transfer inhibits hypoxia-induced proliferation of retinal microvascular endothelial cells in vitro. Int J Ophthalmol. 5:562–569. 2012.PubMed/NCBI

10 

Mintz-Hittner HA: Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors. Early Hum Dev. 88:937–941. 2012. View Article : Google Scholar : PubMed/NCBI

11 

Martínez-Castellanos MA, Schwartz S, Hernández-Rojas ML, Kon-Jara VA, García-Aguirre G, Guerrero-Naranjo JL, Chan RV and Quiroz-Mercado H: Long-term effect of antiangiogenic therapy for retinopathy of prematurity up to 5 years of follow-up. Retina. 33:329–338. 2013. View Article : Google Scholar

12 

Hanna M, Liu H, Amir J, Sun Y, Morris SW, Siddiqui MA, Lau LF and Chaqour B: Mechanical regulation of the proangiogenic factor CCN1/CYR61 gene requires the combined activities of MRTF-A and CREB-binding protein histone acetyltransferase. J Biol Chem. 284:23125–23136. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Jun JI and Lau LF: Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov. 10:945–963. 2011. View Article : Google Scholar : PubMed/NCBI

14 

Brigstock DR: The connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed (CCN) family. Endocr Rev. 20:189–206. 1999.PubMed/NCBI

15 

Brigstock DR: The CCN family: a new stimulus package. J Endocrinol. 178:169–175. 2003. View Article : Google Scholar : PubMed/NCBI

16 

Brigstock DR: Regulation of angiogenesis and endothelial cell function by connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61). Angiogenesis. 5:153–165. 2002. View Article : Google Scholar

17 

Yan L and Chaqour B: Cysteine-rich protein 61 (CCN1) and connective tissue growth factor (CCN2) at the crosshairs of ocular neovascular and fibrovascular disease therapy. J Cell Commun Signal. 7:253–263. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Choi J, Lin A, Shrier E, Lau LF, Grant MB and Chaqour B: Degradome products of the matricellular protein CCN1 as modulators of pathological angiogenesis in the retina. J Biol Chem. 288:23075–23089. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Chen CC and Lau LF: Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol. 41:771–783. 2009. View Article : Google Scholar :

20 

Yang XM, Wang YS, Zhang J, Li Y, Xu JF, Zhu J, Zhao W, Chu DK and Wiedemann P: Role of PI3K/Akt and MEK/ERK in mediating hypoxia-induced expression of HIF-1alpha and VEGF in laser-induced rat choroidal neovascularization. Invest Ophthalmol Vis Sci. 50:1873–1879. 2009. View Article : Google Scholar

21 

You JJ, Yang CH, Yang CM and Chen MS: Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin ανβ3, FAK, PI3K/Akt, and NF-κB pathways in retinal vascular endothelial cells. Cell Signal. 26:133–140. 2014. View Article : Google Scholar

22 

Sasore T, Reynolds AL and Kennedy BN: Targeting the PI3K/Akt/mTOR pathway in ocular neovascularization. Adv Exp Med Biol. 801:805–811. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Guo H, Lv Y, Tian T, Hu TH, Wang WJ, Sui X, Jiang L, Ruan ZP and Nan KJ: Downregulation of p57 accelerates the growth and invasion of hepatocellular carcinoma. Carcinogenesis. 32:1897–1904. 2011. View Article : Google Scholar : PubMed/NCBI

24 

Han Z, Yang Q, Liu B, Wu J, Li Y, Yang C and Jiang Y: MicroRNA-622 functions as a tumor suppressor by targeting K-Ras and enhancing the anticarcinogenic effect of resveratrol. Carcinogenesis. 33:131–139. 2012. View Article : Google Scholar

25 

Aubry JP, Blaecke A, Lecoanet-Henchoz S, Jeannin P, Herbault N, Caron G, Moine V and Bonnefoy JY: Annexin V used for measuring apoptosis in the early events of cellular cytotoxicity. Cytometry. 37:197–204. 1999. View Article : Google Scholar : PubMed/NCBI

26 

Vermes I, Haanen C, Steffens-Nakken H and Reutelingsperger C: A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods. 184:39–51. 1995. View Article : Google Scholar : PubMed/NCBI

27 

Smith LE, Wesolowski E, McLellan A, Kostyk SK, D'Amato R, Sullivan R and D'Amore PA: Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci. 35:101–111. 1994.PubMed/NCBI

28 

Masuda I, Matsuo T, Yasuda T and Matsuo N: Gene transfer with liposomes to the intraocular tissues by different routes of administration. Invest Ophthalmol Vis Sci. 37:1914–1920. 1996.PubMed/NCBI

29 

You JJ, Yang CH, Chen MS and Yang CM: Cysteine-rich 61, a member of the CCN family, as a factor involved in the pathogenesis of proliferative diabetic retinopathy. Invest Ophthalmol Vis Sci. 50:3447–3455. 2009. View Article : Google Scholar : PubMed/NCBI

30 

Zhang Q, Zhang J, Guan Y, Zhang S, Zhu C, Xu GT and Wang L: Suppression of retinal neovascularization by the iNOS inhibitor aminoguanidine in mice of oxygen-induced retinopathy. Graefes Arch Clin Exp Ophthalmol. 247:919–927. 2009. View Article : Google Scholar : PubMed/NCBI

31 

Hasan A, Pokeza N, Shaw L, Lee HS, Lazzaro D, Chintala H, Rosenbaum D, Grant MB and Chaqour B: The matricellular protein cysteine-rich protein 61 (CCN1/Cyr61) enhances physiological adaptation of retinal vessels and reduces pathological neovascularization associated with ischemic retinopathy. J Biol Chem. 286:9542–9554. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Lambert V, Lecomte J, Hansen S, Blacher S, Gonzalez ML, Struman I, Sounni NE, Rozet E, de Tullio P, Foidart JM, et al: Laser-induced choroidal neovascularization model to study age-related macular degeneration in mice. Nat Protoc. 8:2197–2211. 2013. View Article : Google Scholar : PubMed/NCBI

33 

Ecoiffier T, Yuen D and Chen L: Differential distribution of blood and lymphatic vessels in the murine cornea. Invest Ophthalmol Vis Sci. 51:2436–2440. 2010. View Article : Google Scholar :

34 

Barnett JM, McCollum GW, Fowler JA, Duan JJ, Kay JD, Liu RQ, Bingaman DP and Penn JS: Pharmacologic and genetic manipulation of MMP-2 and -9 affects retinal neovascularization in rodent models of OIR. Invest Ophthalmol Vis Sci. 48:907–915. 2007. View Article : Google Scholar : PubMed/NCBI

35 

Park K, Chen Y, Hu Y, Mayo AS, Kompella UB, Longeras R and Ma JX: Nanoparticle-mediated expression of an angiogenic inhibitor ameliorates ischemia-induced retinal neovascularization and diabetes-induced retinal vascular leakage. Diabetes. 58:1902–1913. 2009. View Article : Google Scholar : PubMed/NCBI

36 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar

37 

Smith LE: Pathogenesis of retinopathy of prematurity. Acta Paediatr Suppl. 91:26–28. 2002. View Article : Google Scholar : PubMed/NCBI

38 

Grote K, Salguero G, Ballmaier M, Dangers M, Drexler H and Schieffer B: The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration. Blood. 110:877–885. 2007. View Article : Google Scholar : PubMed/NCBI

39 

Leu SJ, Lam SC and Lau LF: Pro-angiogenic activities of CYR61 (CCN1) mediated through integrins alphavbeta3 and alpha6beta1 in human umbilical vein endothelial cells. J Biol Chem. 277:46248–46255. 2002. View Article : Google Scholar : PubMed/NCBI

40 

Kireeva ML, Latinkić BV, Kolesnikova TV, Chen CC, Yang GP, Abler AS and Lau LF: Cyr61 and Fisp12 are both ECM-associated signaling molecules: Activities, metabolism, and localization during development. Exp Cell Res. 233:63–77. 1997. View Article : Google Scholar : PubMed/NCBI

41 

Kireeva ML, Mo FE, Yang GP and Lau LF: Cyr61, a product of a growth factor-inducible immediate-early gene, promotes cell proliferation, migration, and adhesion. Mol Cell Biol. 16:1326–1334. 1996. View Article : Google Scholar : PubMed/NCBI

42 

Zhang X, Yu W and Dong F: Cysteine-rich 61 (CYR61) is up-regulated in proliferative diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 250:661–668. 2012. View Article : Google Scholar

43 

Meyuhas R, Pikarsky E, Tavor E, Klar A, Abramovitch R, Hochman J, Lago TG and Honigman A: A Key role for cyclic AMP-responsive element binding protein in hypoxia-mediated activation of the angiogenesis factor CCN1 (CYR61) in Tumor cells. Mol Cancer Res. 6:1397–1409. 2008. View Article : Google Scholar : PubMed/NCBI

44 

Leask A: CCN1: A novel target for pancreatic cancer. J Cell Commun Signal. 5:123–124. 2011. View Article : Google Scholar : PubMed/NCBI

45 

Perbal B: CCN proteins: multifunctional signalling regulators. Lancet. 363:62–64. 2004. View Article : Google Scholar : PubMed/NCBI

46 

Su BC and Mo FE: CCN1 enables Fas ligand-induced apoptosis in cardiomyoblast H9c2 cells by disrupting caspase inhibitor XIAP. Cell Signal. 26:1326–1334. 2014. View Article : Google Scholar : PubMed/NCBI

47 

Gerszten RE, Friedrich EB, Matsui T, Hung RR, Li L, Force T and Rosenzweig A: Role of phosphoinositide 3-kinase in monocyte recruitment under flow conditions. J Biol Chem. 276:26846–26851. 2001. View Article : Google Scholar : PubMed/NCBI

48 

Zheng ZZ and Liu ZX: Activation of the phosphatidylinositol 3-kinase/protein kinase Akt pathway mediates CD151-induced endothelial cell proliferation and cell migration. Int J Biochem Cell Biol. 39:340–348. 2007. View Article : Google Scholar

49 

Quan Y, Wang N, Chen Q, Xu J, Cheng W, Di M, Xia W and Gao WQ: SIRT3 inhibits prostate cancer by destabilizing oncoprotein c-MYC through regulation of the PI3K/Aktpathway. Oncotarget. 6:26494–26507. 2015. View Article : Google Scholar : PubMed/NCBI

50 

Long QZ, Zhou M, Liu XG, Du YF, Fan JH, Li X and He DL: Interaction of CCN1 with αvβ3 integrin induces P-glycoprotein and confers vinblastine resistance in renal cell carcinoma cells. Anticancer Drugs. 24:810–817. 2013. View Article : Google Scholar : PubMed/NCBI

51 

Lin BR, Chang CC, Chen LR, Wu MH, Wang MY, Kuo IH, Chu CY, Chang KJ, Lee PH, Chen WJ, et al: Cysteine-rich 61 (CCN1) enhances chemotactic migration, transendothelial cell migration, and intravasation by concomitantly up-regulating chemokine receptor 1 and 2. Mol Cancer Res. 5:1111–1123. 2007. View Article : Google Scholar : PubMed/NCBI

52 

Lin MT, Kuo IH, Chang CC, Chu CY, Chen HY, Lin BR, Sureshbabu M, Shih HJ and Kuo ML: Involvement of hypoxia-inducing factor-1alpha-dependent plasminogen activator inhibitor-1 up-regulation in Cyr61/CCN1-induced gastric cancer cell invasion. J Biol Chem. 283:15807–15815. 2008. View Article : Google Scholar : PubMed/NCBI

53 

Hanrahan F, Humphries P and Campbell M: RNAi-mediated barrier modulation: synergies of the brain and eye. Ther Deliv. 1:587–594. 2010. View Article : Google Scholar : PubMed/NCBI

54 

Roy S, Nasser S, Yee M, Graves DT and Roy S: A long-term siRNA strategy regulates fibronectin overexpression and improves vascular lesions in retinas of diabetic rats. Mol Vis. 17:3166–3174. 2011.PubMed/NCBI

55 

Kuwabara K, Ogawa S, Matsumoto M, Koga S, Clauss M, Pinsky DJ, Lyn P, Leavy J, Witte L and Joseph-Silverstein J: Hypoxia-mediated induction of acidic/basic fibroblast growth factor and platelet-derived growth factor in mononuclear phagocytes stimulates growth of hypoxic endothelial cells. Proc Natl Acad Sci USA. 92:4606–4610. 1995. View Article : Google Scholar : PubMed/NCBI

56 

Kunz M, Hartmann A, Flory E, Toksoy A, Koczan D, Thiesen HJ, Mukaida N, Neumann M, Rapp UR, Bröcker EB and Gillitzer R: Anoxia-induced up-regulation of interleukin-8 in human malignant melanoma. A potential mechanism for high tumor aggressiveness. Am J Pathol. 155:753–763. 1999. View Article : Google Scholar : PubMed/NCBI

57 

Yamashita K, Discher DJ, Hu J, Bishopric NH and Webster KA: Molecular regulation of the endothelin-1 gene by hypoxia. Contributions of hypoxia-inducible factor-1, activator protein-1, GATA-2, AND p300/CBP. J Biol Chem. 276:12645–12653. 2001. View Article : Google Scholar : PubMed/NCBI

58 

Woo KJ, Lee TJ, Park JW and Kwon TK: Desferrioxamine, an iron chelator, enhances HIF-1alpha accumulation via cyclooxy-genase-2 signaling pathway. Biochem Biophys Res Commun. 343:8–14. 2006. View Article : Google Scholar : PubMed/NCBI

59 

You JJ, Yang CM, Chen MS and Yang CH: Regulation of Cyr61/CCN1 expression by hypoxia through cooperation of c-Jun/AP-1 and HIF-1α in retinal vascular endothelial cells. Exp Eye Res. 91:825–836. 2010. View Article : Google Scholar : PubMed/NCBI

60 

Chaqour B and Goppelt-Struebe M: Mechanical regulation of the Cyr61/CCN1 and CTGF/CCN2 proteins. FEBS J. 273:3639–3649. 2006. View Article : Google Scholar : PubMed/NCBI

61 

Lee HY, Chung JW, Youn SW, Kim JY, Park KW, Koo BK, Oh BH, Park YB, Chaqour B, Walsh K and Kim HS: Forkhead transcription factor FOXO3a is a negative regulator of angiogenic immediate early gene CYR61, leading to inhibition of vascular smooth muscle cell proliferation and neointimal hyperplasia. Circ Res. 100:372–380. 2007. View Article : Google Scholar : PubMed/NCBI

62 

Chen CC, Chen N and Lau LF: The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts. J Biol Chem. 276:10443–10452. 2001. View Article : Google Scholar

63 

Murphy LO, MacKeigan JP and Blenis J: A network of immediate early gene products propagates subtle differences in mitogen-activated protein kinase signal amplitude and duration. Mol Cell Biol. 24:144–153. 2004. View Article : Google Scholar :

64 

Mo FE, Muntean AG, Chen CC, Stolz DB, Watkins SC and Lau LF: CYR61 (CCN1) is essential for placental development and vascular integrity. Mol Cell Biol. 22:8709–8720. 2002. View Article : Google Scholar : PubMed/NCBI

65 

Zhong H, De Marzo AM, Laughner E, Lim M, Hilton DA, Zagzag D, Buechler P, Isaacs WB, Semenza GL and Simons JW: Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res. 59:5830–5835. 1999.PubMed/NCBI

66 

Chaqour B: Molecular control of vascular development by the matricellular proteins CCN1 (Cyr61) and CCN2 (CTGF). Trends Dev Biol. 7:59–72. 2013.

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Copy and paste a formatted citation
Spandidos Publications style
Di Y, Zhang Y, Nie Q and Chen X: CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy. Int J Mol Med 36: 1507-1518, 2015.
APA
Di, Y., Zhang, Y., Nie, Q., & Chen, X. (2015). CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy. International Journal of Molecular Medicine, 36, 1507-1518. https://doi.org/10.3892/ijmm.2015.2371
MLA
Di, Y., Zhang, Y., Nie, Q., Chen, X."CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy". International Journal of Molecular Medicine 36.6 (2015): 1507-1518.
Chicago
Di, Y., Zhang, Y., Nie, Q., Chen, X."CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy". International Journal of Molecular Medicine 36, no. 6 (2015): 1507-1518. https://doi.org/10.3892/ijmm.2015.2371
Copy and paste a formatted citation
x
Spandidos Publications style
Di Y, Zhang Y, Nie Q and Chen X: CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy. Int J Mol Med 36: 1507-1518, 2015.
APA
Di, Y., Zhang, Y., Nie, Q., & Chen, X. (2015). CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy. International Journal of Molecular Medicine, 36, 1507-1518. https://doi.org/10.3892/ijmm.2015.2371
MLA
Di, Y., Zhang, Y., Nie, Q., Chen, X."CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy". International Journal of Molecular Medicine 36.6 (2015): 1507-1518.
Chicago
Di, Y., Zhang, Y., Nie, Q., Chen, X."CCN1/Cyr61-PI3K/AKT signaling promotes retinal neovascularization in oxygen-induced retinopathy". International Journal of Molecular Medicine 36, no. 6 (2015): 1507-1518. https://doi.org/10.3892/ijmm.2015.2371
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