Role of vascular endothelial growth factor and its receptors in the corneal tissue and corneal lesions

Abstract

Abstract:

BACKGROUND: Vascular endothelial growth factors are a family of multifunctional cytokines that can enhance vascular permeability, induce angiogenesis, promote endothelial cell growth and migration, and inhibit cell apoptosis.
OBJECTIVE: To elaborate the latest progress in the role of vascular endothelial growth factor and its receptors in the corneal tissue.
METHODS: A computer-based search of PubMed databases was performed for relevant articles published from 2005 to 2015. The key words were “vascular endothelial growth factor, cornea”. According to the inclusion and exclusion criteria, 43 articles were included in result analysis.
RESULTS AND CONCLUSION: Vascular endothelial growth factor and its receptors are involved in the regulation of corneal neovascularization by causing Tip cell activation that affects the Notch signaling pathways. Corneal lymphatic regeneration mainly relies on macrophages to secrete vascular endothelial growth factor-C or vascular endothelial growth factor-D that further activate vascular endothelial growth factor receptor-3 in the lymphatic endothelial cells to cause cell proliferation and migration, and eventually lead to the formation of new lymphatic vessels. But herpes simplex keratitis HSK induces the corneal lymphatic regeneration by vascular endothelial growth factor-A/vascular endothelial growth factor receptor-2 pathway. Vascular endothelial growth factor family can significantly improve the damaged corneal nerve endings, epithelium and corneal sensitivity, has the function of nerve nutrition and promote restoration of the corneal epithelium.

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

Feng Lu, Di Guo-hu, Zhou Qing-jun. Role of vascular endothelial growth factor and its receptors in the corneal tissue and corneal lesions[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(11): 1644-1650.

Figures/Tables 1

References

[1] Yang X, Zhang Y, Hosaka K, et al. VEGF-B promotes cancer metastasis through a VEGF-A-independent mechanism and serves as a marker of poor prognosis for cancer patients. Proc Natl Acad Sci U S A.2015; 112(22):E2900-2909.

[2] Tewari KS, Sill MW, Long HJ 3rd, et al. Improved survival with bevacizumab in advanced cervical cancer. N Engl J Med.2014;370(8):734-743.

[3] de Groot JF, Lamborn KR, Chang SM,et al. Phase II study of aflibercept in recurrent malignant glioma: a North American Brain Tumor Consortium study.J Clin Oncol. 2011;29(19):2689-2695.

[4] Martin DF, Maguire MG, Ying GS, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med. 2011;364(20):1897-1908.

[5] Li X, Xu G, Wang Y, et al. Safety and efficacy of conbercept in neovascular age-related macular degeneration: results from a 12-month randomized phase 2 study: AURORA study. Ophthalmology. 2014; 121(9):1740-1747.

[6] Scott AW, Bressler SB. Long-term follow-up of vascular endothelial growth factor inhibitor therapy for neovascular age-related macular degeneration.Curr Opin Ophthalmol. 2013;24(3):190-196.

[7] Saharinen P, Eklund L, Pulkki K, et al. VEGF and angiopoietin signaling in tumor angiogenesis and metastasis. Trends Mol Med. 2011;17(7):347-62.

[8] Lin YD, Luo CY, Hu YN, et al. Instructive nanofiber scaffolds with VEGF create a microenvironment for arteriogenesis and cardiac repair. Sci Transl Med. 2012;4(146):146ra109.

[9] Foxton RH, Finkelstein A, Vijay S, et al. VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma. Am J Pathol. 2013; 182(4):1379-1390.

[10] Guaiquil VH, Pan Z, Karagianni N, et al. VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions. Proc Natl Acad Sci USA. 2014;111(48):17272-17277.

[11] Shibuya M. Vascular endothelial growth factor and its receptor system: physiological functions in angiogenesis and pathological roles in various diseases. J Biochem. 2013;153(1):13-19.

[12] Albuquerque RJ.The newest member of the VEGF family.Blood. 2013;121(20):4015-4016.

[13] Nowak DG, Woolard J, Amin EM, et al. Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors. J Cell Sci. 2008;121(Pt 20):3487-95.

[14] Hua J, Spee C, Kase S, et al. Recombinant human VEGF165b inhibits experimental choroidal neovascularization. Invest Ophthalmol Vis Sci. 2010; 51(8):4282-4288.

[15] Lee SH, Jeong D, Han YS,et al. Pivotal role of vascular endothelial growth factor pathway in tumor angiogenesis. Ann Surg Treat Res. 2015;89(1):1-8.

[16] Jussila L, Alitalo K.Vascular growth factors and lymphangiogenesis.Physiol Rev.2002;82:673–700.

[17] Ambati BK, Nozaki M, Singh N, et al. Corneal avascularity is due to soluble VEGF receptor-1. Nature. 2006;443(7114):993-997.

[18] Albuquerque RJC, Hayashi T, Cho WG, et al. Alternatively spliced VEGF receptor-2 is an essential endogenous inhibitor of lymphatic vessels. Nat Med. 2009;15(9):1023-1030.

[19] Singh N, Tiem M, Watkins R, et al. Soluble vascular endothelial growth factor receptor 3 is essential for corneal alymphaticity. Blood. 2013;121(20):4242-4249.

[20] Cursiefen C, Chen L, Saint-Geniez M,et al. Nonvascular VEGF receptor 3 expression by corneal epithelium maintains avascularity and vision. Proc Natl Acad Sci USA. 2006;103(30):11405-11410.

[21] Siemerink MJ, Klaassen I, Van Noorden CJ, et al. Endothelial Tip cells in ocular angiogenesis: potential target for anti-angiogenesis therapy. J Histochem Cytochem. 2013;61:101-115.

[22] Benedito R, Hellström M. Notch as a hub for signaling in angiogenesis. Exp Cell Res. 2013;319:1281-1288.

[23] Lobov IB, Renard RA, Papadopoulos N, et al. Delta-like ligand 4 (Dll4) is induced by VEGF as a negative regulator of angiogenic sprouting. Proc Natl Acad Sci USA. 2007;104: 3219-3224.

[24] Hellstrom M, Phng LK, Hofmann JJ, et al. Dll4 signalling through Notch1 regulates formation of Tip cells during angiogenesis. Nature. 2007;445:776-780.

[25] Benedito R, Roca C, Sorensen I, et al. The notch ligands Dll4 and Jagged1 have opposing effects on angiogenesis. Cell. 2009;137:1124-1135.

[26] Philipp W, Speicher L, Humpel C.Expression of vascular endothelial growth factor and its receptors in inflamed and vascularized human corneas. Invest Ophthalmol Vis Sci. 2000;41(9):2514-2522.

[27] Zhou Q, Yang L, Qu M, et al. Role of senescent fibroblasts on alkali-induced corneal neovascularization. J Cell Physiol. 2012;227: 1148-1156.

[28] Li ZR, Li YP, Lin ML, et al. Activated macrophages induce neovascularization through upregulation of MMP-9 and VEGF in rat corneas. Cornea. 2012; 31(9):1028-1035.

[29] Cursiefen C, Chen L, Borges LP, et al. VEGF-A stimulates lymphangiogenesis and hemangiogenesis in inflammatory neovascularization via macrophage recruitment. J Clin Invest. 2004;113(7):1040-1050.

[30] Dou GR, Wang YC, Hu XB, et al. RBP-J, the transcription factor downstream of Notch receptors, is essential for the maintenance of vascular homeostasis in adult mice. FASEB J. 2008;22:1606-1617.

[31] Maruyama K, Nakazawa T, Cursiefen C, et al. The maintenance of lymphatic vessels in the cornea is dependent on the presence of macrophages.Invest Ophthalmol Vis Sci. 2012;53(6):3145-3153.

[32] Wuest TR, Carr DJJ. VEGF-A expression by HSV-1–infected cells drives corneal lymphangiogenesis. J Exp Med. 2010;207(1):101-115.

[33] Ruiz de Almodovar C, Fabre PJ, Knevels E, et al. VEGF mediates commissural axon chemoattraction through its receptor Flk1. Neuron. 2011;70(5):966-978.

[34] Poesen K, Lambrechts D, Van Damme P, et al. Novel role for vascular endothelial growth factor (VEGF) receptor-1 and its ligand VEGF-B in motor neuron degeneration. J Neurosci. 2008; 28(42):10451–10459.

[35] Carmeliet P, Ruiz de Almodovar C. VEGF ligands and receptors: Implications in neurodevelopment and neurodegeneration. Cell Mol Life Sci. 2013;70(10): 1763-1778.

[36] Foxton RH, Finkelstein A, Vijay S, et al. VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma. Am J Pathol. 2013; 182(4):1379-1390.

[37] Pan Z, Fukuoka S, Karagianni N, et al. Vascular endothelial growth factor promotes anatomical and functional recovery of injured peripheral nerves in the avascular cornea. FASEB J. 2013;27(7):2756-2767.

[38] Li Z, Burns AR, Han L, et al. IL-17 and VEGF Are Necessary for Efficient Corneal Nerve Regeneration. Am J Pathol. 2011;178(3):1106-1116.

[39] Petsoglou C, Balaggan KS, Dart JK, et al. Subconjunctival bevacizumab induces regression of corneal neovascularisation: a pilot randomised placebo-controlled double-masked trial. Br J Ophthalmol. 2013;97(1):28-32.

[40] Bucher F, Parthasarathy A, Bergua A, et al. Topical Ranibizumab inhibits inflammatory corneal hem- and lymphangiogenesis. Acta Ophthalmol. 2014;92(2): 143-148.

[41] Park YR, Chung SK. Inhibitory Effect of Topical Aflibercept on Corneal Neovascularization in Rabbits. Cornea. 2015;34(10):1303-1307.

[42] Qazi Y, Stagg B, Singh N, et al. Nanoparticle-mediated delivery of shRNA.VEGF-a plasmids regresses corneal neovascularization. Invest Ophthalmol Vis Sci. 2012;53(6):2837-2844.

[43] Chen WL, Chen YM, Chu HS, et al. Mechanisms controlling the effects of bevacizumab (avastin) on the inhibition of early but not late formed corneal neovascularization. PLoS One. 2014;9(4):e94205.