nach oben

Erschienen in:

01.07.2014 | Review Paper

In vitro and ex vivo retina angiogenesis assays

verfasst von: Sara Rezzola, Mirella Belleri, Giuseppina Gariano, Domenico Ribatti, Ciro Costagliola, Francesco Semeraro, Marco Presta

Erschienen in: Angiogenesis | Ausgabe 3/2014

Einloggen, um Zugang zu erhalten

Abstract

Pathological angiogenesis of the retina is a key component of irreversible causes of blindness, as observed in proliferative diabetic retinopathy, age-related macular degeneration, and retinopathy of prematurity. Seminal studies in the early 1980 s about the angiogenic activity exerted by mammalian retinal tissue extracts on the chick embryo chorioallantoic membrane and the later discovery of vascular endothelial growth factor (VEGF) accumulation in eyes of patients with diabetic retinopathy paved the way for the development of anti-angiogenic VEGF blockers for the treatment of retinal neovascularization. Since then, numerous preclinical and clinical studies about diabetic retinopathy and other retinal disorders have opened new lines of angiogenesis inquiry, indicating that limitations to anti-VEGF therapies may exist. Moreover, the production of growth factors other than VEGF may affect the response to anti-VEGF approaches. Thus, experimental models of retinal angiogenesis remain crucial for investigating novel anti-angiogenic therapies and bringing them to patients. To this aim, in vitro and ex vivo angiogenesis assays may be suitable for a rapid screening of potential anti-angiogenic molecules before in vivo validation of the putative lead compounds. This review focuses on the different in vitro and ex vivo angiogenesis assays that have been developed over the years based on the isolation of endothelial cells from the retina of various animal species and ex vivo cultures of neonatal and adult retina explants. Also, recent observations have shown that eye neovascularization in zebrafish (Danio rerio) embryos, an in vivo animal platform experimentally analogous to in vitro/ex vivo models, may represent a novel target for the identification of angiogenesis inhibitors. When compared to in vivo assays, in vitro and ex vivo models of retina neovascularization, including zebrafish embryo, may represent cost-effective and rapid tools for the screening of novel anti-angiogenic therapeutics.

Carmeliet P, Jain RK (2011) Molecular mechanisms and clinical applications of angiogenesis. Nature 473:298–307PubMedCentralPubMed

Mechoulam H, Pierce EA (2003) Retinopathy of prematurity: molecular pathology and therapeutic strategies. Am J Pharmacogenomics 3:261–277PubMed

Chen J, Stahl A, Hellstrom A, Smith LE (2011) Current update on retinopathy of prematurity: screening and treatment. Curr Opin Pediatr 23:173–178PubMedCentralPubMed

Congdon N, O’Colmain B, Klaver CC, Klein R, Munoz B, Friedman DS, Kempen J, Taylor HR, Mitchell P (2004) Causes and prevalence of visual impairment among adults in the United States. Arch Ophthalmol 122:477–485PubMed

Klein BE (2007) Overview of epidemiologic studies of diabetic retinopathy. Ophthalmic Epidemiol 14:179–183PubMed

Semeraro F, Parrinello G, Cancarini A, Pasquini L, Zarra E, Cimino A, Cancarini G, Valentini U, Costagliola C (2011) Predicting the risk of diabetic retinopathy in type 2 diabetic patients. J Diabetes Complicat 25:292–297PubMed

Friedman DS, O’Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J (2004) Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol 122:564–572PubMed

Gariano RF, Gardner TW (2005) Retinal angiogenesis in development and disease. Nature 438:960–966PubMed

Siemerink MJ, Augustin AJ, Schlingemann RO (2010) Mechanisms of ocular angiogenesis and its molecular mediators. Dev Ophthalmol 46:4–20PubMed

10.

Antonetti DA, Klein R, Gardner TW (2012) Diabetic retinopathy. N Engl J Med 366:1227–1239PubMed

11.

Kim LA, D’Amore PA (2012) A brief history of anti-VEGF for the treatment of ocular angiogenesis. Am J Pathol 181:376–379PubMed

12.

Miller JW, Le Couter J, Strauss EC, Ferrara N (2013) Vascular endothelial growth factor a in intraocular vascular disease. Ophthalmology 120:106–114PubMed

13.

Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE et al (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487PubMed

14.

Costagliola C, Agnifili L, Arcidiacono B, Duse S, Fasanella V, Mastropasqua R, Verolino M, Semeraro F (2012) Systemic thromboembolic adverse events in patients treated with intravitreal anti-VEGF drugs for neovascular age-related macular degeneration. Expert Opin Biol Ther 12:1299–1313PubMed

15.

Stewart MW (2012) The expanding role of vascular endothelial growth factor inhibitors in ophthalmology. Mayo Clin Proc 87:77–88PubMedCentralPubMed

16.

Montezuma SR, Vavvas D, Miller JW (2009) Review of the ocular angiogenesis animal models. Semin Ophthalmol 24:52–61PubMed

17.

Stahl A, Connor KM, Sapieha P, Chen J, Dennison RJ, Krah NM, Seaward MR, Willett KL, Aderman CM, Guerin KI, Hua J, Lofqvist C, Hellstrom A, Smith LE (2010) The mouse retina as an angiogenesis model. Invest Ophthalmol Vis Sci 51:2813–2826PubMedCentralPubMed

18.

Wells DJ (2011) Animal welfare and the 3Rs in European biomedical research. Ann NY Acad Sci 1245:14–16PubMed

19.

Goodwin AM (2007) In vitro assays of angiogenesis for assessment of angiogenic and anti-angiogenic agents. Microvasc Res 74:172–183PubMedCentralPubMed

20.

Staton CA, Reed MW, Brown NJ (2009) A critical analysis of current in vitro and in vivo angiogenesis assays. Int J Exp Pathol 90:195–221PubMedCentralPubMed

21.

Bastaki M, Nelli EE, Dell’Era P, Rusnati M, Molinari-Tosatti MP, Parolini S, Auerbach R, Ruco LP, Possati L, Presta M (1997) Basic fibroblast growth factor-induced angiogenic phenotype in mouse endothelium. A study of aortic and microvascular endothelial cell lines. Arterioscler Thromb Vasc Biol 17:454–464PubMed

22.

Chi JT, Chang HY, Haraldsen G, Jahnsen FL, Troyanskaya OG, Chang DS, Wang Z, Rockson SG, van de Rijn M, Botstein D, Brown PO (2003) Endothelial cell diversity revealed by global expression profiling. Proc Natl Acad Sci USA 100:10623–10628PubMedCentralPubMed

23.

Stewart EA, Samaranayake GJ, Browning AC, Hopkinson A, Amoaku WM (2011) Comparison of choroidal and retinal endothelial cells: characteristics and response to VEGF isoforms and anti-VEGF treatments. Exp Eye Res 93:761–766PubMed

24.

Zetter BR (1988) Endothelial heterogeneity: influence of vessel size, organ localization, and species specificity on the properties of cultured endothelial cells. In: Ryan (ed) Endothelial cells, vol. 2. CRC Press, Boca Raton, USA pp 64–79

25.

Henkind P, Wise GN (1974) Retinal neovascularization, collaterals, and vascular shunts. Br J Ophthalmol 58:413–422PubMedCentralPubMed

26.

Adamis AP, Aiello LP, D’Amato RA (1999) Angiogenesis and ophthalmic disease. Angiogenesis 3:9–14PubMed

27.

Terry TL (1942) Fibroblastic overgrowth of persistent Tunica Vasculosa Lentis in infants born prematurely: II. Report of cases-clinical aspects. Trans Am Ophthalmol Soc 40:262–284PubMedCentralPubMed

28.

Chen J, Smith LE (2007) Retinopathy of prematurity. Angiogenesis 10:133–140PubMed

29.

Hughes S, Yang H, Chan-Ling T (2000) Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis. Invest Ophthalmol Vis Sci 41:1217–1228PubMed

30.

Ashton N, Ward B, Serpell G (1954) Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasia. Br J Ophthalmol 38:397–432PubMedCentralPubMed

31.

Kuo HK, Chen CC, Chen YH, Huang HC, Liu CA, Chen FS, Chung MY (2012) Incidence and result of treatment-demanding retinopathy of prematurity using revised U.S. screening guidelines. Am J Perinatol 29:827–831PubMed

32.

Jawa A, Kcomt J, Fonseca VA (2004) Diabetic nephropathy and retinopathy. Med Clin North Am 88:1001–1036PubMed

33.

Group TETDRSR (1987) Photocoagulation for diabetic macular edema: early treatment diabetic retinopathy study report no. 4. Int Ophthalmol Clin 27:265–272

34.

Group ETDRSR (1985) Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report number 1. Arch Ophthalmol 103:1796–1806

35.

Jager RD, Mieler WF, Miller JW (2008) Age-related macular degeneration. N Engl J Med 358:2606–2617PubMed

36.

Resnikoff S, Pascolini D, Etya’ale D, Kocur I, Pararajasegaram R, Pokharel GP, Mariotti SP (2004) Global data on visual impairment in the year 2002. Bull World Health Organ 82:844–851PubMedCentralPubMed

37.

Klein R, Peto T, Bird A, Vannewkirk MR (2004) The epidemiology of age-related macular degeneration. Am J Ophthalmol 137:486–495PubMed

38.

Wong TY, Scott IU (2010) N Engl J Med. Clinical practice. Retinal-vein occlusion 363:2135–2144

39.

Mitchell P, Smith W, Chang A (1996) Prevalence and associations of retinal vein occlusion in Australia. The Blue Mountains Eye Study. Arch Ophthalmol 114:1243–1247PubMed

40.

Klein R, Moss SE, Meuer SM, Klein BE (2008) The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study. Arch Ophthalmol 126:513–518PubMed

41.

McIntosh RL, Rogers SL, Lim L, Cheung N, Wang JJ, Mitchell P, Kowalski JW, Nguyen HP, Wong TY (2010) Natural history of central retinal vein occlusion: an evidence-based systematic review. Ophthalmology 117:1113–1123PubMed

42.

Group TCVOS (1995) Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The central vein occlusion study group M report. Ophthalmology 102:1425–1433

43.

Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jiao J, Li XY, Whitcup SM, Li J (2011) Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology 118:2453–2460PubMed

44.

Jonas JB, Akkoyun I, Kamppeter B, Kreissig I, Degenring RF (2005) Intravitreal triamcinolone acetonide for treatment of central retinal vein occlusion. Eur J Ophthalmol 15:751–758PubMed

45.

Michaelson M (1948) The mode of development of the vascular system of the retina with some observations on its significance for certain retinal diseases. Trans Ophthalmol Soc UK 68:117–137

46.

Glaser BM, D’Amore PA, Michels RG, Patz A, Fenselau A (1980) Demonstration of vasoproliferative activity from mammalian retina. J Cell Biol 84:298–304PubMed

47.

D’Amore PA, Glaser BM, Brunson SK, Fenselau AH (1981) Angiogenic activity from bovine retina: partial purification and characterization. Proc Natl Acad Sci USA 78:3068–3072PubMedCentralPubMed

48.

Kissun RD, Hill CR, Garner A, Phillips P, Kumar S, Weiss JB (1982) A low-molecular-weight angiogenic factor in cat retina. Br J Ophthalmol 66:165–169PubMedCentralPubMed

49.

Elstow SF, Schor AM, Weiss JB (1985) Bovine retinal angiogenesis factor is a small molecule (molecular mass less than 600). Invest Ophthalmol Vis Sci 26:74–79PubMed

50.

Wang S, Park JK, Duh EJ (2012) Novel targets against retinal angiogenesis in diabetic retinopathy. Curr Diab Rep 12:355–363PubMed

51.

Sherris D (2007) Ocular drug development–future directions. Angiogenesis 10:71–76PubMed

52.

Adamis AP, Shima DT (2005) The role of vascular endothelial growth factor in ocular health and disease. Retina 25:111–118PubMed

53.

Ng YS, Krilleke D, Shima DT (2006) VEGF function in vascular pathogenesis. Exp Cell Res 312:527–537PubMed

54.

Penn JS, Madan A, Caldwell RB, Bartoli M, Caldwell RW, Hartnett ME (2008) Vascular endothelial growth factor in eye disease. Prog Retin Eye Res 27:331–371PubMedCentralPubMed

55.

Murata T, Ishibashi T, Khalil A, Hata Y, Yoshikawa H, Inomata H (1995) Vascular endothelial growth factor plays a role in hyperpermeability of diabetic retinal vessels. Ophthalmic Res 27:48–52PubMed

56.

Mathews MK, Merges C, McLeod DS, Lutty GA (1997) Vascular endothelial growth factor and vascular permeability changes in human diabetic retinopathy. Invest Ophthalmol Vis Sci 38:2729–2741PubMed

57.

Kumar B, Gupta SK, Saxena R, Srivastava S (2012) Current trends in the pharmacotherapy of diabetic retinopathy. J Postgrad Med 58:132–139PubMed

58.

Al-Latayfeh M, Silva PS, Sun JK, Aiello LP (2012) Antiangiogenic therapy for ischemic retinopathies. Cold Spring Harb Perspect Med 2:a006411PubMedCentralPubMed

59.

Ruckman J, Green LS, Beeson J, Waugh S, Gillette WL, Henninger DD, Claesson-Welsh L, Janjic N (1998) 2′-Fluoropyrimidine RNA-based aptamers to the 165-amino acid form of vascular endothelial growth factor (VEGF165). Inhibition of receptor binding and VEGF-induced vascular permeability through interactions requiring the exon 7-encoded domain. J Biol Chem 273:20556–20567PubMed

60.

Rosenfeld PJ, Schwartz SD, Blumenkranz MS, Miller JW, Haller JA, Reimann JD, Greene WL, Shams N (2005) Maximum tolerated dose of a humanized anti-vascular endothelial growth factor antibody fragment for treating neovascular age-related macular degeneration. Ophthalmology 112:1048–1053PubMed

61.

Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS (2002) VEGF-Trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 99:11393–11398PubMedCentralPubMed

62.

Rosenfeld PJ, Fung AE, Puliafito CA (2005) Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for macular edema from central retinal vein occlusion. Ophthalmic Surg Lasers Imaging 36:336–339PubMed

63.

Martinez-Castellanos MA, Schwartz S, Hernandez-Rojas ML, Kon-Jara VA, Garcia-Aguirre G, Guerrero-Naranjo JL, Chan RV, Quiroz-Mercado H (2013) Long-term effect of antiangiogenic therapy for retinopathy of prematurity up to 5 years of follow-up. Retina 33:329–338PubMed

64.

Wu WC, Kuo HK, Yeh PT, Yang CM, Lai CC, Chen SN (2013) An updated study of the use of bevacizumab in the treatment of patients with prethreshold retinopathy of prematurity in taiwan. Am J Ophthalmol 155:150–158PubMed

65.

Mintz-Hittner HA (2012) Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors. Early Hum Dev 88:937–941PubMed

66.

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

67.

Nguyen QD, Shah SM, Khwaja AA, Channa R, Hatef E, Do DV, Boyer D, Heier JS, Abraham P, Thach AB, Lit ES, Foster BS, Kruger E, Dugel P, Chang T, Das A, Ciulla TA, Pollack JS, Lim JI, Eliott D, Campochiaro PA (2010) Two-year outcomes of the ranibizumab for edema of the mAcula in diabetes (READ-2) study. Ophthalmology 117:2146–2151PubMed

68.

Massin P, Bandello F, Garweg JG, Hansen LL, Harding SP, Larsen M, Mitchell P, Sharp D, Wolf-Schnurrbusch UE, Gekkieva M, Weichselberger A, Wolf S (2010) Safety and efficacy of ranibizumab in diabetic macular edema (RESOLVE Study): a 12-month, randomized, controlled, double-masked, multicenter phase II study. Diabetes Care 33:2399–2405PubMedCentralPubMed

69.

Mitchell P, Bandello F, Schmidt-Erfurth U, Lang GE, Massin P, Schlingemann RO, Sutter F, Simader C, Burian G, Gerstner O, Weichselberger A (2011) The RESTORE study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology 118:615–625PubMed

70.

Nguyen QD, Brown DM, Marcus DM, Boyer DS, Patel S, Feiner L, Gibson A, Sy J, Rundle AC, Hopkins JJ, Rubio RG, Ehrlich JS (2012) Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 119:789–801PubMed

71.

Do DV, Schmidt-Erfurth U, Gonzalez VH, Gordon CM, Tolentino M, Berliner AJ, Vitti R, Ruckert R, Sandbrink R, Stein D, Yang K, Beckmann K, Heier JS (2011) The DA VINCI Study: phase 2 primary results of VEGF Trap-Eye in patients with diabetic macular edema. Ophthalmology 118:1819–1826PubMed

72.

Do DV, Nguyen QD, Boyer D, Schmidt-Erfurth U, Brown DM, Vitti R, Berliner AJ, Gao B, Zeitz O, Ruckert R, Schmelter T, Sandbrink R, Heier JS (2012) One-year outcomes of the DA VINCI Study of VEGF Trap-Eye in eyes with diabetic macular edema. Ophthalmology 119:1658–1665PubMed

73.

Gupta N, Mansoor S, Sharma A, Sapkal A, Sheth J, Falatoonzadeh P, Kuppermann B, Kenney M (2013) Diabetic retinopathy and VEGF. Open Ophthalmol J 7:4–10PubMedCentralPubMed

74.

Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY (2010) Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology 117:1124–1133PubMed

75.

Campochiaro PA, Brown DM, Awh CC, Lee SY, Gray S, Saroj N, Murahashi WY, Rubio RG (2011) Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study. Ophthalmology 118:2041–2049PubMed

76.

Epstein DL, Algvere PV, von Wendt G, Seregard S, Kvanta A (2012) Benefit from bevacizumab for macular edema in central retinal vein occlusion: twelve-month results of a prospective, randomized study. Ophthalmology 119:2587–2591PubMed

77.

Boyer D, Heier J, Brown DM, Clark WL, Vitti R, Berliner AJ, Groetzbach G, Zeitz O, Sandbrink R, Zhu X, Beckmann K, Haller JA (2012) Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology 119:1024–1032PubMed

78.

Brown DM, Heier JS, Clark WL, Boyer DS, Vitti R, Berliner AJ, Zeitz O, Sandbrink R, Zhu X, Haller JA (2013) Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J Ophthalmol 155:429–437PubMed

79.

Holz FG, Roider J, Ogura Y, Korobelnik JF, Simader C, Groetzbach G, Vitti R, Berliner AJ, Hiemeyer F, Beckmann K, Zeitz O, Sandbrink R (2013) VEGF Trap-Eye for macular oedema secondary to central retinal vein occlusion: 6-month results of the phase III GALILEO study. Br J Ophthalmol 97:278–284PubMed

80.

Palii SS, Caballero S Jr, Shapiro G, Grant MB (2007) Medical treatment of diabetic retinopathy with somatostatin analogues. Expert Opin Investig Drugs 16:73–82PubMed

81.

Palmer GM, Tiran Z, Zhou Z, Capozzi ME, Park W, Coletta C, Pyriochou A, Kliger Y, Levy O, Borukhov I, Dewhirst MW, Rotman G, Penn JS, Papapetropoulos A (2012) A novel angiopoietin-derived peptide displays anti-angiogenic activity and inhibits tumour-induced and retinal neovascularization. Br J Pharmacol 165:1891–1903PubMedCentralPubMed

82.

Rennel ES, Regula JT, Harper SJ, Thomas M, Klein C, Bates DO (2011) A human neutralizing antibody specific to Ang-2 inhibits ocular angiogenesis. Microcirculation 18:598–607PubMed

83.

Akiyama H, Kachi S, Silva RL, Umeda N, Hackett SF, McCauley D, McCauley T, Zoltoski A, Epstein DM, Campochiaro PA (2006) Intraocular injection of an aptamer that binds PDGF-B: a potential treatment for proliferative retinopathies. J Cell Physiol 207:407–412PubMed

84.

Chen J, Connor KM, Aderman CM, Smith LE (2008) Erythropoietin deficiency decreases vascular stability in mice. J Clin Invest 118:526–533PubMedCentralPubMed

85.

Ghasemi H, Ghazanfari T, Yaraee R, Faghihzadeh S, Hassan ZM (2011) Roles of IL-8 in ocular inflammations: a review. Ocul Immunol Inflamm 19:401–412PubMed

86.

Butler JM, Guthrie SM, Koc M, Afzal A, Caballero S, Brooks HL, Mames RN, Segal MS, Grant MB, Scott EW (2005) SDF-1 is both necessary and sufficient to promote proliferative retinopathy. J Clin Invest 115:86–93PubMedCentralPubMed

87.

Lima e Silva R, Shen J, Hackett SF, Kachi S, Akiyama H, Kiuchi K, Yokoi K, Hatara MC, Lauer T, Aslam S, Gong YY, Xiao WH, Khu NH, Thut C, Campochiaro PA (2007) The SDF-1/CXCR4 ligand/receptor pair is an important contributor to several types of ocular neovascularization. FASEB J 21:3219–3230PubMed

88.

van Wijngaarden P, Qureshi SH (2008) Inhibitors of vascular endothelial growth factor (VEGF) in the management of neovascular age-related macular degeneration: a review of current practice. Clin Exp Optom 91:427–437PubMed

89.

Kieran MW, Kalluri R, Cho YJ (2012) The VEGF pathway in cancer and disease: responses, resistance, and the path forward. Cold Spring Harb Perspect Med 2:a006593PubMed

90.

Tranos P, Vakalis A, Asteriadis S, Koukoula S, Vachtsevanos A, Perganta G, Georgalas I (2013) Resistance to antivascular endothelial growth factor treatment in age-related macular de generation. Drug Des Dev Ther 7:485–490

91.

Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, Pyles EA, Yancopoulos GD, Stahl N, Wiegand SJ (2012) Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis 15:171–185PubMedCentralPubMed

92.

Bharadwaj AS, Appukuttan B, Wilmarth PA, Pan Y, Stempel AJ, Chipps TJ, Benedetti EE, Zamora DO, Choi D, David LL, Smith JR (2013) Role of the retinal vascular endothelial cell in ocular disease. Prog Retin Eye Res 32:102–180PubMedCentralPubMed

93.

Haribalaganesh R, Banumathi E, Sheikpranbabu S, Deepak V, Sirishkumar N, Gurunathan S (2010) Isolation and characterization of goat retinal microvascular endothelial cells. In Vitro Cell Dev Biol Anim 46:529–537PubMed

94.

Matsubara TA, Murata TA, Wu GS, Barron EA, Rao NA (2000) Isolation and culture of rat retinal microvessel endothelial cells using magnetic beads coated with antibodies to PECAM-1. Curr Eye Res 20:1–7PubMed

95.

Xiaozhuang Z, Xianqiong L, Jingbo J, Shuiqing H, Jie Y, Yunbin C (2010) Isolation and characterization of fetus human retinal microvascular endothelial cells. Ophthalmic Res 44:125–130PubMed

96.

Su X, Sorenson CM, Sheibani N (2003) Isolation and characterization of murine retinal endothelial cells. Mol Vis 9:171–178PubMed

97.

Su T, Gillies MC (1992) A simple method for the in vitro culture of human retinal capillary endothelial cells. Invest Ophthalmol Vis Sci 33:2809–2813PubMed

98.

Banumathi E, Haribalaganesh R, Babu SS, Kumar NS, Sangiliyandi G (2009) High-yielding enzymatic method for isolation and culture of microvascular endothelial cells from bovine retinal blood vessels. Microvasc Res 77:377–381PubMed

99.

Yu L, Liang XH, Ferrara N (2011) Comparing protein VEGF inhibitors: in vitro biological studies. Biochem Biophys Res Commun 408:276–281PubMed

100.

Hata Y, Miura M, Nakao S, Kawahara S, Kita T, Ishibashi T (2008) Antiangiogenic properties of fasudil, a potent Rho-Kinase inhibitor. Jpn J Ophthalmol 52:16–23PubMed

101.

Yoshida T, Gong J, Xu Z, Wei Y, Duh EJ (2012) Inhibition of pathological retinal angiogenesis by the integrin alphavbeta3 antagonist tetraiodothyroacetic acid (tetrac). Exp Eye Res 94:41–48PubMedCentralPubMed

102.

Cano Mdel V, Karagiannis ED, Soliman M, Bakir B, Zhuang W, Popel AS, Gehlbach PL (2009) A peptide derived from type 1 thrombospondin repeat-containing protein WISP-1 inhibits corneal and choroidal neovascularization. Invest Ophthalmol Vis Sci 50:3840–3845PubMed

103.

Boosani CS, Nalabothula N, Sheibani N, Sudhakar A (2010) Inhibitory effects of arresten on bFGF-induced proliferation, migration, and matrix metalloproteinase-2 activation in mouse retinal endothelial cells. Curr Eye Res 35:45–55PubMedCentralPubMed

104.

Jiang A, Gao H, Kelley MR, Qiao X (2011) Inhibition of APE1/Ref-1 redox activity with APX3330 blocks retinal angiogenesis in vitro and in vivo. Vis Res 51:93–100PubMedCentralPubMed

105.

Park SW, Cho CS, Jun HO, Ryu NH, Kim JH, Yu YS, Kim JS (2012) Anti-angiogenic effect of luteolin on retinal neovascularization via blockade of reactive oxygen species production. Invest Ophthalmol Vis Sci 53:7718–7726PubMed

106.

Premanand C, Rema M, Sameer MZ, Sujatha M, Balasubramanyam M (2006) Effect of curcumin on proliferation of human retinal endothelial cells under in vitro conditions. Invest Ophthalmol Vis Sci 47:2179–2184PubMed

107.

Maines LW, French KJ, Wolpert EB, Antonetti DA, Smith CD (2006) Pharmacologic manipulation of sphingosine kinase in retinal endothelial cells: implications for angiogenic ocular diseases. Invest Ophthalmol Vis Sci 47:5022–5031PubMedCentralPubMed

108.

Hata Y, Miura M, Asato R, Kita T, Oba K, Kawahara S, Arita R, Kohno R, Nakao S, Ishibashi T (2010) Antiangiogenic mechanisms of simvastatin in retinal endothelial cells. Graefes Arch Clin Exp Ophthalmol 248:667–673PubMed

109.

Arnaoutova I, George J, Kleinman HK, Benton G (2009) The endothelial cell tube formation assay on basement membrane turns 20: state of the science and the art. Angiogenesis 12:267–274PubMed

110.

DeNiro M, Alsmadi O, Al-Mohanna F (2009) Modulating the hypoxia-inducible factor signaling pathway as a therapeutic modality to regulate retinal angiogenesis. Exp Eye Res 89:700–717PubMed

111.

Yang Y, Yang K, Li Y, Li X, Sun Q, Meng H, Zeng Y, Hu Y, Zhang Y (2013) Decursin inhibited proliferation and angiogenesis of endothelial cells to suppress diabetic retinopathy via VEGFR2. Mol Cell Endocrinol. Epub ahead of print

112.

Deissler HL, Deissler H, Lang GE (2012) Actions of bevacizumab and ranibizumab on microvascular retinal endothelial cells: similarities and differences. Br J Ophthalmol 96:1023–1028PubMedCentralPubMed

113.

Rusovici R, Patel CJ, Chalam KV (2013) Bevacizumab inhibits proliferation of choroidal endothelial cells by regulation of the cell cycle. Clin Ophthalmol 7:321–327PubMedCentralPubMed

114.

Grigsby JG, Parvathaneni K, Almanza MA, Botello AM, Mondragon AA, Allen DM, Tsin AT (2011) Effects of tamoxifen versus raloxifene on retinal capillary endothelial cell proliferation. J Ocul Pharmacol Ther 27:225–233PubMedCentralPubMed

115.

Zheng Y, Gu Q, Xu X (2012) Inhibition of ocular neovascularization by a novel peptide derived from human placenta growth factor-1. Acta Ophthalmol 90:e512–e523PubMed

116.

Xu Y, Zhao H, Zheng Y, Gu Q, Ma J, Xu X (2010) A novel antiangiogenic peptide derived from hepatocyte growth factor inhibits neovascularization in vitro and in vivo. Mol Vis 16:1982–1995PubMedCentralPubMed

117.

Ribatti D, Crivellato E (2012) “Sprouting angiogenesis”, a reappraisal. Dev Biol 372:157–165PubMed

118.

Im E, Venkatakrishnan A, Kazlauskas A (2005) Cathepsin B regulates the intrinsic angiogenic threshold of endothelial cells. Mol Biol Cell 16:3488–3500PubMedCentralPubMed

119.

Huxlin KR, Sefton AJ, Furby J (1992) Explantation of fetal murine retinae to the chorioallantoic membrane of the chicken embryo. J Neurosci Methods 41:53–64PubMed

120.

Sawamiphak S, Ritter M, Acker-Palmer A (2010) Preparation of retinal explant cultures to study ex vivo tip endothelial cell responses. Nat Protoc 5:1659–1665PubMed

121.

Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu ME, Acker T, Acker-Palmer A (2010) Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis. Nature 465:487–491PubMed

122.

Murakami T, Suzuma K, Takagi H, Kita M, Ohashi H, Watanabe D, Ojima T, Kurimoto M, Kimura T, Sakamoto A, Unoki N, Yoshimura N (2006) Time-lapse imaging of vitreoretinal angiogenesis originating from both quiescent and mature vessels in a novel ex vivo system. Invest Ophthalmol Vis Sci 47:5529–5536PubMed

123.

Unoki N, Murakami T, Nishijima K, Ogino K, van Rooijen N, Yoshimura N (2010) SDF-1/CXCR4 contributes to the activation of tip cells and microglia in retinal angiogenesis. Invest Ophthalmol Vis Sci 51:3362–3371PubMed

124.

Unoki N, Murakami T, Ogino K, Nukada M, Yoshimura N (2010) Time-lapse imaging of retinal angiogenesis reveals decreased development and progression of neovascular sprouting by anecortave desacetate. Invest Ophthalmol Vis Sci 51:2347–2355PubMed

125.

Knott RM, Robertson M, Muckersie E, Folefac VA, Fairhurst FE, Wileman SM, Forrester JV (1999) A model system for the study of human retinal angiogenesis: activation of monocytes and endothelial cells and the association with the expression of the monocarboxylate transporter type 1 (MCT-1). Diabetologia 42:870–877PubMed

126.

Shafiee A, Penn JS, Krutzsch HC, Inman JK, Roberts DD, Blake DA (2000) Inhibition of retinal angiogenesis by peptides derived from thrombospondin-1. Invest Ophthalmol Vis Sci 41:2378–2388PubMed

127.

Brown KC, Lau JK, Dom AM, Witte TR, Luo H, Crabtree CM, Shah YH, Shiflett BS, Marcelo AJ, Proper NA, Hardman WE, Egleton RD, Chen YC, Mangiarua EI, Dasgupta P (2012) MG624, an alpha7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway. Angiogenesis 15:99–114PubMed

128.

Rezzola S, Belleri M, Ribatti D, Costagliola C, Presta M, Semeraro F (2013) A novel ex vivo murine retina angiogenesis (EMRA) assay. Exp Eye Res 112C:51–56

129.

Kobayashi T, Yamanaka T, Jacobs JM, Teixeira F, Suzuki K (1980) The Twitcher mouse: an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease). Brain Res 202:479–483PubMed

130.

Suzuki K, Suzuki Y (1970) Globoid cell leucodystrophy (Krabbe’s disease): deficiency of galactocerebroside beta-galactosidase. Proc Natl Acad Sci USA 66:302–309PubMedCentralPubMed

131.

Belleri M, Ronca R, Coltrini D, Nico B, Ribatti D, Poliani PL, Giacomini A, Alessi P, Marchesini S, Santos MB, Bongarzone ER, Presta M (2013) Inhibition of angiogenesis by beta-galactosylceramidase deficiency in globoid cell leukodystrophy. Brain 136:2859–2875PubMed

132.

Pichler FB, Laurenson S, Williams LC, Dodd A, Copp BR, Love DR (2003) Chemical discovery and global gene expression analysis in zebrafish. Nat Biotechnol 21:879–883PubMed

133.

Lawson ND, Wolfe SA (2011) Forward and reverse genetic approaches for the analysis of vertebrate development in the zebrafish. Dev Cell 21:48–64PubMed

134.

Meng X, Noyes MB, Zhu LJ, Lawson ND, Wolfe SA (2008) Targeted gene inactivation in zebrafish using engineered zinc-finger nucleases. Nat Biotechnol 26:695–701PubMedCentralPubMed

135.

Funfak A, Brosing A, Brand M, Kohler JM (2007) Micro fluid segment technique for screening and development studies on Danio rerio embryos. Lab Chip 7:1132–1138PubMed

136.

Isogai S, Horiguchi M, Weinstein BM (2001) The vascular anatomy of the developing zebrafish: an atlas of embryonic and early larval development. Dev Biol 230:278–301PubMed

137.

Weinstein BM (2002) Plumbing the mysteries of vascular development using the zebrafish. Semin Cell Dev Biol 13:515–522PubMed

138.

Gore AV, Monzo K, Cha YR, Pan W, Weinstein BM (2012) Vascular development in the zebrafish. Cold Spring Harb Perspect Med 2:a006684PubMedCentralPubMed

139.

Weinstein BM, Stemple DL, Driever W, Fishman MC (1995) Gridlock, a localized heritable vascular patterning defect in the zebrafish. Nat Med 1:1143–1147PubMed

140.

Lawson ND, Weinstein BM (2002) In vivo imaging of embryonic vascular development using transgenic zebrafish. Dev Biol 248:307–318PubMed

141.

Kamei M, Isogai S, Pan W, Weinstein BM (2010) Imaging blood vessels in the zebrafish. Methods Cell Biol 100:27–54PubMed

142.

Peterson RT, Link BA, Dowling JE, Schreiber SL (2000) Small molecule developmental screens reveal the logic and timing of vertebrate development. Proc Natl Acad Sci USA 97:12965–12969PubMedCentralPubMed

143.

Zon LI, Peterson RT (2005) In vivo drug discovery in the zebrafish. Nat Rev Drug Discov 4:35–44PubMed

144.

Choi J, Dong L, Ahn J, Dao D, Hammerschmidt M, Chen JN (2007) FoxH1 negatively modulates flk1 gene expression and vascular formation in zebrafish. Dev Biol 304:735–744PubMedCentralPubMed

145.

Alvarez Y, Cederlund ML, Cottell DC, Bill BR, Ekker SC, Torres-Vazquez J, Weinstein BM, Hyde DR, Vihtelic TS, Kennedy BN (2007) Genetic determinants of hyaloid and retinal vasculature in zebrafish. BMC Dev Biol 7:114PubMedCentralPubMed

146.

Kim JH, Park JA, Lee SW, Kim WJ, Yu YS, Kim KW (2006) Blood-neural barrier: intercellular communication at glio-vascular interface. J Biochem Mol Biol 39:339–345PubMed

147.

Gestri G, Link BA, Neuhauss SC (2012) The visual system of zebrafish and its use to model human ocular diseases. Dev Neurobiol 72:302–327PubMedCentralPubMed

148.

Alvarez Y, Chen K, Reynolds AL, Waghorne N, O’Connor JJ, Kennedy BN (2010) Predominant cone photoreceptor dysfunction in a hyperglycaemic model of non-proliferative diabetic retinopathy. Dis Model Mech 3:236–245PubMed

149.

Criswick VG, Schepens CL (1969) Familial exudative vitreoretinopathy. Am J Ophthalmol 68:578–594PubMed

150.

Collin RW, Nikopoulos K, Dona M, Gilissen C, Hoischen A, Boonstra FN, Poulter JA, Kondo H, Berger W, Toomes C, Tahira T, Mohn LR, Blokland EA, Hetterschijt L, Ali M, Groothuismink JM, Duijkers L, Inglehearn CF, Sollfrank L, Strom TM, Uchio E, van Nouhuys CE, Kremer H, Veltman JA, van Wijk E, Cremers FP (2013) ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature. Proc Natl Acad Sci USA 110:9856–9861PubMedCentralPubMed

151.

Kitambi SS, McCulloch KJ, Peterson RT, Malicki JJ (2009) Small molecule screen for compounds that affect vascular development in the zebrafish retina. Mech Dev 126:464–477PubMedCentralPubMed

152.

Ferrara N (2004) Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 25:581–611PubMed

153.

Serbedzija GN, Flynn E, Willett CE (1999) Zebrafish angiogenesis: a new model for drug screening. Angiogenesis 3:353–359PubMed

154.

Alvarez Y, Astudillo O, Jensen L, Reynolds AL, Waghorne N, Brazil DP, Cao Y, O’Connor JJ, Kennedy BN (2009) Selective inhibition of retinal angiogenesis by targeting PI3 kinase. PLoS ONE 4:e7867PubMedCentralPubMed

155.

Pugh CW, Ratcliffe PJ (2003) Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med 9:677–684PubMed

156.

Cao Z, Jensen LD, Rouhi P, Hosaka K, Lanne T, Steffensen JF, Wahlberg E, Cao Y (2010) Hypoxia-induced retinopathy model in adult zebrafish. Nat Protoc 5:1903–1910PubMed

157.

Chew EY (2005) Ocular manifestations of von Hippel-Lindau disease: clinical and genetic investigations. Trans Am Ophthalmol Soc 103:495–511PubMedCentralPubMed

158.

Arjamaa O, Nikinmaa M (2006) Oxygen-dependent diseases in the retina: role of hypoxia-inducible factors. Exp Eye Res 83:473–483PubMed

159.

van Rooijen E, Voest EE, Logister I, Bussmann J, Korving J, van Eeden FJ, Giles RH, Schulte-Merker S (2010) von Hippel-Lindau tumor suppressor mutants faithfully model pathological hypoxia-driven angiogenesis and vascular retinopathies in zebrafish. Dis Model Mech 3:343–353PubMed

160.

Gnarra JR, Ward JM, Porter FD, Wagner JR, Devor DE, Grinberg A, Emmert-Buck MR, Westphal H, Klausner RD, Linehan WM (1997) Defective placental vasculogenesis causes embryonic lethality in VHL-deficient mice. Proc Natl Acad Sci USA 94:9102–9107PubMedCentralPubMed

161.

Belleri M, Ribatti D, Nicoli S, Cotelli F, Forti L, Vannini V, Stivala LA, Presta M (2005) Antiangiogenic and vascular-targeting activity of the microtubule-destabilizing trans-resveratrol derivative 3,5,4′-trimethoxystilbene. Mol Pharmacol 67:1451–1459PubMed

Titel: In vitro and ex vivo retina angiogenesis assays
verfasst von: Sara Rezzola
Mirella Belleri
Giuseppina Gariano
Domenico Ribatti
Ciro Costagliola
Francesco Semeraro
Marco Presta
Publikationsdatum: 01.07.2014
Verlag: Springer Netherlands
Erschienen in: Angiogenesis / Ausgabe 3/2014
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI: https://doi.org/10.1007/s10456-013-9398-x

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 3/2014

Anti-angiogenic therapy for cancer: current progress, unresolved questions and future directions

Heparan sulfate in angiogenesis: a target for therapy

VEGFA gene locus analysis across 80 human tumour types reveals gene amplification in several neoplastic entities

5th International meeting on angiogenesis

Modulation of angiogenesis by thyroid hormone and hormone analogues: implications for cancer management