Elevated Levels of Endoglin, Endostatin, FGF-α, HGF, and Thrombospondin-2 in Aqueous Humor of nAMD Patients

References

• Resnikoff S, Pascolini D, Etya’ale D, et al. Global data on visual impairment in the year 2002. Bull World Health Organ. 2004;82:844–851.
   PubMed Web of Science ®Google Scholar
• Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2:e106–116. doi:10.1016/S2214-109X(13)70145-1.
   PubMed Web of Science ®Google Scholar
• Schmidt-Erfurth U, Chong V, Loewenstein A, et al. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br J Ophthalmol. 2014;98:1144–1167. doi:10.1136/bjophthalmol-2014-305702.
   PubMed Web of Science ®Google Scholar
• Balasubramanian SA, Krishna Kumar K, Baird PN. The role of proteases and inflammatory molecules in triggering neovascular age-related macular degeneration: basic science to clinical relevance. Transl Res. 2014;164:179–192. doi:10.1016/j.trsl.2014.04.005.
   PubMed Web of Science ®Google Scholar
• Spaide RF, Yannuzzi LA, Slakter JS, Sorenson J, Orlach DA. Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy. Retina. 1995;15:100–110. doi:10.1097/00006982-199515020-00003.
   PubMed Web of Science ®Google Scholar
• Desmettre TJ. Epigenetics in age-related macular degeneration (AMD). J Fr Ophtalmol. 2018;41:e407–e415. doi:10.1016/j.jfo.2018.09.001.
   PubMed Web of Science ®Google Scholar
• Ambati J, Atkinson JP, Gelfand BD. Immunology of age-related macular degeneration. Nat Rev Immunol. 2013;13:438–451. doi:10.1038/nri3459.
   PubMed Web of Science ®Google Scholar
• Kauppinen A, Paterno JJ, Blasiak J, Salminen A, Kaarniranta K. Inflammation and its role in age-related macular degeneration. Cell Mol Life Sci. 2016;73:1765–1786.
   PubMed Web of Science ®Google Scholar
• Al-Khersan H, Hussain RM, Ciulla TA, Dugel PU. Innovative therapies for neovascular age-related macular degeneration. Expert Opin Pharmacother. 2019;20:1879–1891. doi:10.1080/14656566.2019.1636031.
   PubMed Web of Science ®Google Scholar
• Liu K, Song Y, Xu G, et al. Conbercept for treatment of neovascular age-related macular degeneration: results of the randomized phase 3 phoenix study. Am J Ophthalmol. 2019;197:156–167. doi:10.1016/j.ajo.2018.08.026.
   PubMed Web of Science ®Google Scholar
• Peng Y, Zhang X, Li M, et al. Short-term efficacy of intravitreal conbercept in treatment-naive patients with polypoidal choroidal vasculopathy. Drug Des Devel Ther. 2018;12:339–345. doi:10.2147/DDDT.S158368.
   PubMed Web of Science ®Google Scholar
• Chang AA, Li H, Broadhead GK, et al. Intravitreal aflibercept for treatment-resistant neovascular age-related macular degeneration. Ophthalmology. 2014;121:188–192. doi:10.1016/j.ophtha.2013.08.035.
   PubMed Web of Science ®Google Scholar
• Saito M, Kano M, Itagaki K, Oguchi Y, Sekiryu T. Switching to intravitreal aflibercept injection for polypoidal choroidal vasculopathy refractory to ranibizumab. Retina. 2014;34:2192–2201. doi:10.1097/IAE.0000000000000236.
   PubMed Web of Science ®Google Scholar
• Yerramothu P. New Therapies of Neovascular AMD-Beyond Anti-VEGFs. Vision. 2018;2. doi:10.3390/vision2030031.
   Google Scholar
• Hernandez-Zimbron LF, Zamora-Alvarado R, Ochoa-de la Paz L, et al. Age-related macular degeneration: new paradigms for treatment and management of AMD. Oxid Med Cell Longev. 2018;2018:8374647. doi:10.1155/2018/8374647.
   PubMed Web of Science ®Google Scholar
• Agawa T, Usui Y, Wakabayashi Y, et al. Profile of intraocular immune mediators in patients with age-related macular degeneration and the effect of intravitreal bevacizumab injection. Retina. 2014;34:1811–1818. doi:10.1097/IAE.0000000000000157.
   PubMed Web of Science ®Google Scholar
• Zhou H, Zhao X, Yuan M, Chen Y. Comparison of cytokine levels in the aqueous humor of polypoidal choroidal vasculopathy and neovascular age-related macular degeneration patients. BMC Ophthalmol. 2020;20:15. doi:10.1186/s12886-019-1278-8.
   PubMed Web of Science ®Google Scholar
• Motohashi R, Noma H, Yasuda K, Kotake O, Goto H, Shimura M. Dynamics of inflammatory factors in aqueous humor during ranibizumab or aflibercept treatment for age-related macular degeneration. Ophthalmic Res. 2017;58:209–216. doi:10.1159/000478705.
   PubMed Web of Science ®Google Scholar
• Agrawal R, Balne PK, Wei X, et al. Cytokine profiling in patients with exudative age-related macular degeneration and polypoidal choroidal vasculopathy. Invest Ophthalmol Vis Sci. 2019;60:376–382. doi:10.1167/iovs.18-24387.
   PubMed Web of Science ®Google Scholar
• Lawler PR, Lawler J. Molecular basis for the regulation of angiogenesis by thrombospondin-1 and −2. Cold Spring Harb Perspect Med. 2012;2:a006627. doi:10.1101/cshperspect.a006627.
   PubMed Web of Science ®Google Scholar
• Muether PS, Neuhann I, Buhl C, Hermann MM, Kirchhof B, Fauser S. Intraocular growth factors and cytokines in patients with dry and neovascular age-related macular degeneration. Retina. 2013;33:1809–1814. doi:10.1097/IAE.0b013e318285cd9e.
   PubMed Web of Science ®Google Scholar
• Wooff Y, Man SM, Aggio-Bruce R, Natoli R, Fernando NIL-1. Family members mediate cell death, inflammation and angiogenesis in retinal degenerative diseases. Front Immunol. 2019;10:1618.
   PubMed Web of Science ®Google Scholar
• Ten Dijke P, Goumans MJ, Pardali E. Endoglin in angiogenesis and vascular diseases. Angiogenesis. 2008;11:79–89. doi:10.1007/s10456-008-9101-9.
   PubMed Web of Science ®Google Scholar
• Nassiri F, Cusimano MD, Scheithauer BW, et al. Endoglin (CD105): a review of its role in angiogenesis and tumor diagnosis, progression and therapy. Anticancer Res. 2011;31:2283–2290.
   PubMed Web of Science ®Google Scholar
• Barnett JM, Suarez S, McCollum GW, Penn JS. Endoglin promotes angiogenesis in cell- and animal-based models of retinal neovascularization. Invest Ophthalmol Vis Sci. 2014;55:6490–6498. doi:10.1167/iovs.14-14945.
   PubMed Web of Science ®Google Scholar
• Duwel A, Eleno N, Jerkic M, et al. Reduced tumor growth and angiogenesis in endoglin- haploinsufficient mice. Tumour Biol. 2007;28:1–8. doi:10.1159/000097040.
   PubMedGoogle Scholar
• Seghers L, de Vries MR, Pardali E, et al. Shear induced collateral artery growth modulated by endoglin but not by ALK1. J Cell Mol Med. 2012;16:2440–2450. doi:10.1111/j.1582-4934.2012.01561.x.
   PubMed Web of Science ®Google Scholar
• Cabral T, Lima LH, Mello LGM, et al. Bevacizumab injection in patients with neovascular age-related macular degeneration increases angiogenic biomarkers. Ophthalmol Retina. 2018;2:31–37. doi:10.1016/j.oret.2017.04.004.
   PubMedGoogle Scholar
• Tatar O, Shinoda K, Adam A, et al. Expression of endostatin in human choroidal neovascular membranes secondary to age-related macular degeneration. Exp Eye Res. 2006;83:329–338. doi:10.1016/j.exer.2005.12.017.
   PubMed Web of Science ®Google Scholar
• Palenski TL, Sorenson CM, Jefcoate CR, Sheibani N. Lack of Cyp1b1 promotes the proliferative and migratory phenotype of perivascular supporting cells. Lab Invest. 2013;93:646–662. doi:10.1038/labinvest.2013.55.
   PubMed Web of Science ®Google Scholar
• Fei P, Palenski TL, Wang S, et al. Thrombospondin-2 expression during retinal vascular development and neovascularization. J Ocul Pharmacol Ther. 2015;31:429–444. doi:10.1089/jop.2014.0151.
   PubMed Web of Science ®Google Scholar
• Farnoodian M, Sorenson CM, Sheibani N. Negative regulators of angiogenesis, ocular vascular homeostasis, and pathogenesis and treatment of exudative AMD. J Ophthalmic Vis Res. 2018;13:470–486. doi:10.4103/jovr.jovr_67_18.
   PubMed Web of Science ®Google Scholar
• Zamiri P, Masli S, Kitaichi N, Taylor AW, Streilein JW. Thrombospondin plays a vital role in the immune privilege of the eye. 2005. Ocul Immunol Inflamm. 2007;15(3):279–294. doi:10.1080/09273940701382432.
   PubMed Web of Science ®Google Scholar
• Winterhoff B, Konecny GE. Targeting fibroblast growth factor pathways in endometrial cancer. Curr Probl Cancer. 2017;41:37–47. doi:10.1016/j.currproblcancer.2016.11.002.
   PubMed Web of Science ®Google Scholar
• Rusnati M, Presta M. Fibroblast growth factors/fibroblast growth factor receptors as targets for the development of anti-angiogenesis strategies. Curr Pharm Des. 2007;13:2025–2044. doi:10.2174/138161207781039689.
   PubMed Web of Science ®Google Scholar
• Zakrzewska M, Marcinkowska E, Wiedlocha A. FGF-1: from biology through engineering to potential medical applications. Crit Rev Clin Lab Sci. 2008;45:91–135. doi:10.1080/10408360701713120.
   PubMed Web of Science ®Google Scholar
• Oladipupo SS, Smith C, Santeford A, et al. Endothelial cell FGF signaling is required for injury response but not for vascular homeostasis. Proc Natl Acad Sci U S A. 2014;111:13379–13384. doi:10.1073/pnas.1324235111.
   PubMed Web of Science ®Google Scholar
• Trusolino L, Comoglio PM. Scatter-factor and semaphorin receptors: cell signalling for invasive growth. Nat Rev Cancer. 2002;2:289–300. doi:10.1038/nrc779.
   PubMed Web of Science ®Google Scholar
• Miura Y, Yanagihara N, Imamura H, et al. Hepatocyte growth factor stimulates proliferation and migration during wound healing of retinal pigment epithelial cells in vitro. Jpn J Ophthalmol. 2003;47:268–275. doi:10.1016/S0021-5155(03)00003-0.
   PubMed Web of Science ®Google Scholar
• Pongsachareonnont P, Mak MYK, Hurst CP, Lam WC. Neovascular age-related macular degeneration: intraocular inflammatory cytokines in the poor responder to ranibizumab treatment. Clin Ophthalmol. 2018;12:1877–1885. doi:10.2147/OPTH.S171636.
   PubMed Web of Science ®Google Scholar
• Jonas JB, Tao Y, Neumaier M, Findeisen P. Cytokine concentration in aqueous humour of eyes with exudative age-related macular degeneration. Acta Ophthalmol. 2012;90(e381–427):388. doi:10.1111/j.1755-3768.2012.02414.x.
   Google Scholar
• Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA. Vascular endothelial growth factor and angiogenesis. Pharmacol Rev. 2004;56:549–580. doi:10.1124/pr.56.4.3.
   PubMed Web of Science ®Google Scholar
• Melincovici CS, Bosca AB, Susman S, et al. Vascular endothelial growth factor (VEGF) - key factor in normal and pathological angiogenesis. Rom J Morphol Embryol. 2018;59:455–467.
   PubMed Web of Science ®Google Scholar
• Rosen LS. Clinical experience with angiogenesis signaling inhibitors: focus on vascular endothelial growth factor (VEGF) blockers. Cancer Control. 2002;9:36–44. doi:10.1177/107327480200902S05.
   PubMedGoogle Scholar
• Yamazaki Y, Morita T. Molecular and functional diversity of vascular endothelial growth factors. Mol Divers. 2006;10:515–527. doi:10.1007/s11030-006-9027-3.
   PubMed Web of Science ®Google Scholar
• Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer. 2011;2:1097–1105. doi:10.1177/1947601911423031.
   PubMedGoogle Scholar
• Campbell M, Doyle SL. Current perspectives on established and novel therapies for pathological neovascularization in retinal disease. Biochem Pharmacol. 2019;164:321–325. doi:10.1016/j.bcp.2019.04.029.
   PubMed Web of Science ®Google Scholar
• Sato T, Takeuchi M, Karasawa Y, Enoki T, Ito M. Intraocular inflammatory cytokines in patients with neovascular age-related macular degeneration before and after initiation of intravitreal injection of anti-VEGF inhibitor. Sci Rep. 2018;8:1098. doi:10.1038/s41598-018-19594-6.
   PubMed Web of Science ®Google Scholar
• Rezar-Dreindl S, Sacu S, Eibenberger K, et al. The intraocular cytokine profile and therapeutic response in persistent neovascular age-related macular degeneration. Invest Ophthalmol Vis Sci. 2016;57:4144–4150. doi:10.1167/iovs.16-19772.
   PubMed Web of Science ®Google Scholar
• Ng DS, Yip YW, Bakthavatsalam M, et al. Elevated angiopoietin 2 in aqueous of patients with neovascular age related macular degeneration correlates with disease severity at presentation. Sci Rep. 2017;7:45081. doi:10.1038/srep45081.
   PubMed Web of Science ®Google Scholar
• Engelbrecht C, Sardinha LR, Rizzo LV. Cytokine and chemokine concentration in the tear of patients with age-related cataract. Curr Eye Res. 2020;45(9):1101–1106. doi:10.1080/02713683.2020.1715445
   PubMed Web of Science ®Google Scholar
• Tong JP, Chan WM, Liu DT, et al. Aqueous humor levels of vascular endothelial growth factor and pigment epithelium-derived factor in polypoidal choroidal vasculopathy and choroidal neovascularization. Am J Ophthalmol. 2006;141:456–462. doi:10.1016/j.ajo.2005.10.012.
   PubMed Web of Science ®Google Scholar
• Roh MI, Kim HS, Song JH, Lim JB, Koh HJ, Kwon OW. Concentration of cytokines in the aqueous humor of patients with naive, recurrent and regressed CNV associated with amd after bevacizumab treatment. Retina. 2009;29:523–529. doi:10.1097/IAE.0b013e318195cb15.
   PubMed Web of Science ®Google Scholar
• Muether PS, Hermann MM, Viebahn U, Kirchhof B, Fauser S. Vascular endothelial growth factor in patients with exudative age-related macular degeneration treated with ranibizumab. Ophthalmology. 2012;119:2082–2086. doi:10.1016/j.ophtha.2012.07.041.
   PubMed Web of Science ®Google Scholar
• Solomon SD, Lindsley K, Vedula SS, Krzystolik MG, Hawkins BS. Anti-vascular endothelial growth factor for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2019;3:CD005139. doi:10.1002/14651858.CD005139.pub4.
   PubMedGoogle Scholar
• Jonas JB, Golubkina L, Spandau UH, Schlichtenbrede F, Libondi T. Intravitreal bevacizumab, plasminogen, and pneumatic retinopexy for subfoveal hemorrhage in age-related macular degeneration. Asia Pac J Ophthalmol (Phila). 2012;1:11–12. doi:10.1097/APO.0b013e31823e5663.
   PubMedGoogle Scholar