Skip to main content

Advertisement

SpringerLink
Log in

Development of the retinal vasculature

  • Original Paper
  • Published:
Angiogenesis Aims and scope Submit manuscript

Abstract

Blood vessels that supply the inner portion of the retina are extensively reorganized during development. The vessel regression, sprouting angiogenesis, vascular remodelling and vessel differentiation events involved critically depend on cell–cell signalling between different cellular components such as neurons, glia, endothelial cells, pericytes and immune cells. Studies in mice using transgenic and gene deletion approaches have started to unravel the genetic basis of some of these signalling pathways and have lead to a much improved understanding of the molecular mechanisms controlling retinal blood vessel behaviour both during development and under pathological conditions. Such insight will provide the basis of future therapeutic approaches aimed at manipulating retinal blood vessels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Watanabe T, Raff MC (1988) Retinal astrocytes are immigrants from the optic nerve. Nature 332:834–837

    Article  PubMed  CAS  Google Scholar 

  2. Stone J, Dreher Z (1987) Relationship between astrocytes, ganglion cells and vasculature of the retina. J Comp Neurol 255:35–49

    Article  PubMed  CAS  Google Scholar 

  3. Fruttiger M, Calver AR, Kruger WH, Mudhar HS, Michalovich D, Takakura N, Nishikawa S, Richardson WD (1996) PDGF mediates a neuron-astrocyte interaction in the developing retina. Neuron 17:1117–1131

    Article  PubMed  CAS  Google Scholar 

  4. Ling TL, Stone J (1988) The development of astrocytes in the cat retina: evidence of migration from the optic nerve. Brain Res 44:73–85

    Article  CAS  Google Scholar 

  5. Schnitzer J (1987) Retinal astrocytes: their restriction to vascularized parts of the mammalian retina. Neurosci Lett 78:29–34

    Article  PubMed  CAS  Google Scholar 

  6. Huxlin KR, Sefton AJ, Furby JH (1992) The origin and development of retinal astrocytes in the mouse. J Neurocytol 21:530–544

    Article  PubMed  CAS  Google Scholar 

  7. Engerman RL (1976) Development of the macular circulation. Invest Ophthalmol 15:835–840

    PubMed  CAS  Google Scholar 

  8. Chu Y, Hughes S, Chan-Ling T (2001) Differentiation and migration of astrocyte precursor cells and astrocytes in human fetal retina: relevance to optic nerve coloboma. FASEB J 15:2013–2015

    PubMed  CAS  Google Scholar 

  9. Mi H, Barres BA (1999) Purification and characterization of astrocyte precursor cells in the developing rat optic nerve. J Neurosci 19:1049–1061

    PubMed  CAS  Google Scholar 

  10. Mudhar HS, Pollock RA, Wang C, Stiles CD, Richardson WD (1993) PDGF and its receptors in the developing rodent retina and optic nerve. Development 118:539–552

    PubMed  CAS  Google Scholar 

  11. Fruttiger M, Calver AR, Richardson WD (2000) Platelet-derived growth factor is constitutively secreted from neuronal cell bodies but not from axons. Curr Biol 10:1283–1286

    Article  PubMed  CAS  Google Scholar 

  12. Fruttiger M (2002) Development of the mouse retinal vasculature: angiogenesis versus vasculogenesis. Invest Ophthalmol Vis Sci 43:522–527

    PubMed  Google Scholar 

  13. Pierce EA, Foley ED, Smith LE (1996) Regulation of vascular endothelial growth factor by oxygen in a model of retinopathy of prematurity. Arch Ophthalmol 114:1219–1218

    PubMed  CAS  Google Scholar 

  14. West H, Richardson WD, Fruttiger M (2005) Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes. Development 132:1855–1862

    Article  PubMed  CAS  Google Scholar 

  15. Stone J, Itin A, Alon T, Pe’er J, Gnessin H, Chan-Ling T, Keshet E (1995) Development of retinal vasculature is mediated by hypoxia-induced vascular endothelial growth factor (VEGF) expression by neuroglia. J Neurosci 15:4738–4747

    PubMed  CAS  Google Scholar 

  16. Miyawaki T, Uemura A, Dezawa M, Yu RT, Ide C, Nishikawa S, Honda Y, Tanabe Y, Tanabe T (2004) Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina. J Neurosci 24:8124–8134

    Article  PubMed  CAS  Google Scholar 

  17. Uemura A, Kusuhara S, Wiegand SJ, Yu RT, Nishikawa S (2006) Tlx acts as a proangiogenic switch by regulating extracellular assembly of fibronectin matrices in retinal astrocytes. J Clin Invest 116:369–377

    Article  PubMed  CAS  Google Scholar 

  18. Risau W (1997) Mechanisms of angiogenesis. Nature 386:671–674

    Article  PubMed  CAS  Google Scholar 

  19. Ashton N (1970) Retinal angiogenesis in the human embryo. Br Med Bull 26:103–106

    PubMed  CAS  Google Scholar 

  20. Chan-Ling T, McLeod DS, Hughes S, Baxter L, Chu Y, Hasegawa T, Lutty GA (2004) Astrocyte-endothelial cell relationships during human retinal vascular development. Invest Ophthalmol Vis Sci 45:2020–2032

    Article  PubMed  Google Scholar 

  21. Chan-Ling TL, Halasz P, Stone J (1990) Development of retinal vasculature in the cat: processes and mechanisms. Curr Eye Res 9:459–478

    PubMed  CAS  Google Scholar 

  22. Flower RW, McLeod DS, Lutty GA, Goldberg B, Wajer SD (1985) Postnatal retinal vascular development of the puppy. Invest Ophthalmol Vis Sci 26:957–968

    PubMed  CAS  Google Scholar 

  23. Hughes S, Yang H, Chan-Ling T (2000) Vascularization of the human fetal retina: roles of vasculogenesis and angiogenesis. Invest Ophthalmol Vis Sci 41:1217–1218

    PubMed  CAS  Google Scholar 

  24. Gariano RF (2003) Cellular mechanisms in retinal vascular development. Prog Retin Eye Res 22:295–306

    Article  PubMed  CAS  Google Scholar 

  25. McLeod DS, Hasegawa T, Prow T, Merges C, Lutty G (2006) The initial fetal human retinal vasculature develops by vasculogenesis. Dev Dyn 235(12):3336–3347

    Google Scholar 

  26. Urbich C, Dimmeler S (2004) Endothelial progenitor cells: characterization and role in vascular biology. Circ Res 95:343–353

    Article  PubMed  CAS  Google Scholar 

  27. Rehman J, Li J, Orschell CM, March KL (2003) Peripheral blood “endothelial progenitor cells” are derived from monocyte/macrophages and secrete angiogenic growth factors. Circulation 107:1164–1169

    Article  PubMed  Google Scholar 

  28. Yamashita J, Itoh H, Hirashima M, Ogawa M, Nishikawa S, Yurugi T, Naito M, Nakao K, Nishikawa S (2000) Flk1-positive cells derived from embryonic stem cells serve as vascular progenitors. Nature 408:92–96

    Article  PubMed  CAS  Google Scholar 

  29. Shalaby F, Rossant J, Yamaguchi TP, Gertsenstein M, Wu XF, Breitman ML, Schuh AC (1995) Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice. Nature 376:62–66

    Article  PubMed  CAS  Google Scholar 

  30. Dumont DJ, Fong GH, Puri MC, Gradwohl G, Alitalo K, Breitman ML (1995) Vascularization of the mouse embryo: a study of flk-1, tek, tie, and vascular endothelial growth factor expression during development. Dev Dyn 203:80–92

    PubMed  CAS  Google Scholar 

  31. Yamaguchi TP, Dumont DJ, Conlon RA, Breitman ML, Rossant J (1993) flk-1, an flt-related receptor tyrosine kinase is an early marker for endothelial cell precursors. Development 118:489–498

    PubMed  CAS  Google Scholar 

  32. Otani A, Kinder K, Ewalt K, Otero FJ, Schimmel P, Friedlander M (2002) Bone marrow-derived stem cells target retinal astrocytes and can promote or inhibit retinal angiogenesis. Nat Med 8:1004–1010

    Article  PubMed  CAS  Google Scholar 

  33. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C (2003) VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161:1163–1177

    Article  PubMed  CAS  Google Scholar 

  34. Ruhrberg C, Gerhardt H, Golding M, Watson R, Ioannidou S, Fujisawa H, Betsholtz C, Shima DT (2002) Spatially restricted patterning cues provided by heparin-binding VEGF-A control blood vessel branching morphogenesis. Genes Dev 16:2684–2698

    Article  PubMed  CAS  Google Scholar 

  35. Marin-Padilla M (1985) Early vascularization of the embryonic cerebral cortex: golgi and electron microscopic studies. J Comp Neurol 241:237–249

    Article  PubMed  CAS  Google Scholar 

  36. Kurz H, Gartner T, Eggli PS, Christ B (1996) First blood vessels in the avian neural tube are formed by a combination of dorsal angioblast immigration and ventral sprouting of endothelial cells. Dev Biol 173:133–147

    Article  PubMed  CAS  Google Scholar 

  37. Eichmann A, le Noble F, Autiero M, Carmeliet P (2005) Guidance of vascular and neural network formation. Curr Opin Neurobiol 15:108–115

    Article  PubMed  CAS  Google Scholar 

  38. Claxton S, Fruttiger M (2004) Periodic Delta-like 4 expression in developing retinal arteries. Gene Expr Patterns 5:123–127

    Article  PubMed  CAS  Google Scholar 

  39. Saint-Geniez M, Masri B, Malecaze F, Knibiehler B, Audigier Y (2002) Expression of the murine msr/apj receptor and its ligand apelin is upregulated during formation of the retinal vessels. Mech Dev 110:183–186

    Article  PubMed  CAS  Google Scholar 

  40. Lu X, le Noble F, Yuan L, Jiang Q, De Lafarge B, Sugiyama D, Breant C, Claes F, De Smet F, Thomas JL, Autiero M, Carmeliet P, Tessier-Lavigne M, Eichmann A (2004) The netrin receptor UNC5B mediates guidance events controlling morphogenesis of the vascular system. Nature 432:179–186

    Article  PubMed  CAS  Google Scholar 

  41. Sainson RC, Aoto J, Nakatsu MN, Holderfield M, Conn E, Koller E, Hughes CC (2005) Cell-autonomous notch signaling regulates endothelial cell branching and proliferation during vascular tubulogenesis. FASEB J 19:1027–1029

    PubMed  CAS  Google Scholar 

  42. Gerhardt H, Betsholtz C (2005) How do endothelial cells orientate? EXS 94:3–15

    Google Scholar 

  43. Carmeliet P, Ng YS, Nuyens D, Theilmeier G, Brusselmans K, Cornelissen I, Ehler E, Kakkar VV, Stalmans I, Mattot V, Perriard JC, Dewerchin M, Flameng W, Nagy A, Lupu F, Moons L, Collen D, D’Amore PA, Shima DT (1999) Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Nat Med 5:495–502

    Article  PubMed  CAS  Google Scholar 

  44. Stalmans I, Ng YS, Rohan R, Fruttiger M, Bouche A, Yuce A, Fujisawa H, Hermans B, Shani M, Jansen S, Hicklin D, Anderson DJ, Gardiner T, Hammes HP, Moons L, Dewerchin M, Collen D, Carmeliet P, D’Amore PA (2002) Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms. J Clin Invest 109:327–336

    Article  PubMed  CAS  Google Scholar 

  45. Dorrell MI, Aguilar E, Friedlander M (2002) Retinal vascular development is mediated by endothelial filopodia, a preexisting astrocytic template and specific R-cadherin adhesion. Invest Ophthalmol Vis Sci 43:3500–3510

    PubMed  Google Scholar 

  46. Klagsbrun M, Eichmann A (2005) A role for axon guidance receptors and ligands in blood vessel development and tumor angiogenesis. Cytokine Growth Factor Rev 16:535–548

    Article  PubMed  CAS  Google Scholar 

  47. Steinbach K, Volkmer H, Schlosshauer B (2002) Semaphorin 3E/collapsin-5 inhibits growing retinal axons. Exp Cell Res 279:52–61

    Article  PubMed  CAS  Google Scholar 

  48. Livesey FJ, Hunt SP (1997) Netrin and netrin receptor expression in the embryonic mammalian nervous system suggests roles in retinal, striatal, nigral, and cerebellar development. Mol Cell Neurosci 8:417–429

    Article  PubMed  CAS  Google Scholar 

  49. Erskine L, Williams SE, Brose K, Kidd T, Rachel RA, Goodman CS, Tessier-Lavigne M, Mason CA (2000) Retinal ganglion cell axon guidance in the mouse optic chiasm: expression and function of robos and slits. J Neurosci 20:4975–4982

    PubMed  CAS  Google Scholar 

  50. Adams RH, Wilkinson GA, Weiss C, Diella F, Gale NW, Deutsch U, Risau W, Klein R (1999) Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis. Genes Dev 13:295–306

    PubMed  CAS  Google Scholar 

  51. Wang HU, Chen ZF, Anderson DJ (1998) Molecular distinction and angiogenic interaction between embryonic arteries and veins revealed by ephrin-B2 and its receptor Eph-B4. Cell 93:741–753

    Article  PubMed  CAS  Google Scholar 

  52. Kertesz N, Krasnoperov V, Reddy R, Leshanski L, Kumar SR, Zozulya S, Gill PS (2006) The soluble extracellular domain of EphB4 (sEphB4) antagonizes EphB4-EphrinB2 interaction, modulates angiogenesis, and inhibits tumor growth. Blood 107:2330–2380

    Article  PubMed  CAS  Google Scholar 

  53. Steinle JJ, Meininger CJ, Chowdhury U, Wu G, Granger HJ (2003) Role of ephrin B2 in human retinal endothelial cell proliferation and migration. Cell Signal 15:1011–1017

    Article  PubMed  CAS  Google Scholar 

  54. Steinle JJ, Meininger CJ, Forough R, Wu G, Wu MH, Granger HJ (2002) Eph B4 receptor signaling mediates endothelial cell migration and proliferation via the phosphatidylinositol 3-kinase pathway. J Biol Chem 277:43830–43835

    Article  PubMed  CAS  Google Scholar 

  55. Kim I, Ryu YS, Kwak HJ, Ahn SY, Oh JL, Yancopoulos GD, Gale NW, Koh GY (2002) EphB ligand, ephrinB2, suppresses the VEGF—and angiopoietin 1-induced Ras/mitogen—activated protein kinase pathway in venous endothelial cells. FASEB J 16:1126–1128

    PubMed  CAS  Google Scholar 

  56. Hughes S, Chang-Ling T (2000) Roles of endothelial cell migration and apoptosis in vascular remodeling during development of the central nervous system. Microcirculation 7:317–333

    Article  PubMed  CAS  Google Scholar 

  57. Ishida S, Yamashiro K, Usui T, Kaji Y, Ogura Y, Hida T, Honda Y, Oguchi Y, Adamis AP (2003) Leukocytes mediate retinal vascular remodeling during development and vaso-obliteration in disease. Nat Med 9:781–788

    Article  PubMed  CAS  Google Scholar 

  58. Checchin D, Sennlaub F, Levavasseur E, Leduc M, Chemtob S (2006) Potential role of microglia in retinal blood vessel formation. Invest Ophthalmol Vis Sci 47:3595–3602

    Article  PubMed  Google Scholar 

  59. Nakatsu MN, Sainson RC, Perez-del-Pulgar S, Aoto JN, Aitkenhead M, Taylor KL, Carpenter PM, Hughes CC (2003) VEGF(121) and VEGF(165) regulate blood vessel diameter through vascular endothelial growth factor receptor 2 in an in vitro angiogenesis model. Lab Invest 83:1873–1885

    Article  PubMed  CAS  Google Scholar 

  60. Vargesson N, Laufer E (2001) Smad7 misexpression during embryonic angiogenesis causes vascular dilation and malformations independently of vascular smooth muscle cell function. Dev Biol 240:499–516

    Article  PubMed  CAS  Google Scholar 

  61. le Noble F, Moyon D, Pardanaud L, Yuan L, Djonov V, Matthijsen R, Breant C, Fleury V, Eichmann A (2004) Flow regulates arterial-venous differentiation in the chick embryo yolk sac. Development 131:361–375

    Article  PubMed  CAS  Google Scholar 

  62. Smith LE, Wesolowski E, McLellan A, Kostyk SK, D’Amato R, Sullivan R, D’Amore PA (1994) Oxygen-induced retinopathy in the mouse. Invest Ophthalmol Vis Sci 35:101–111

    PubMed  CAS  Google Scholar 

  63. Gu X, Samuel S, El Shabrawey M, Caldwell RB, Bartoli M, Marcus DM, Brooks SE (2002) Effects of sustained hyperoxia on revascularization in experimental retinopathy of prematurity. Invest Ophthalmol Vis Sci 43:496–502

    PubMed  Google Scholar 

  64. Gu X, El Remessy AB, Brooks SE, Al Shabrawey M, Tsai NT, Caldwell RB (2003) Hyperoxia induces retinal vascular endothelial cell apoptosis through formation of peroxynitrite. Am J Physiol Cell Physiol 285:C546–C554

    PubMed  CAS  Google Scholar 

  65. Alon T, Hemo I, Itin A, Pe’er J, Stone J, Keshet E (1995) Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. Nat Med 1:1024–1028

    Article  PubMed  CAS  Google Scholar 

  66. Riva CE, Pournaras CJ, Tsacopoulos M (1986) Regulation of local oxygen tension and blood flow in the inner retina during hyperoxia. J Appl Physiol 61:592–598

    PubMed  CAS  Google Scholar 

  67. Claxton S, Fruttiger M (2003) Role of arteries in oxygen induced vaso-obliteration. Exp Eye Res 77:305–311

    Article  PubMed  CAS  Google Scholar 

  68. Chan-Ling T, Page MP, Gardiner T, Baxter L, Rosinova E, Hughes S (2004) Desmin ensheathment ratio as an indicator of vessel stability: evidence in normal development and in retinopathy of prematurity. Am J Pathol 165:1301–1313

    PubMed  CAS  Google Scholar 

  69. Hellstrom M, Kaln M, Lindahl P, Abramsson A, Betsholtz C (1999) Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse. Development 126:3047–3055

    PubMed  CAS  Google Scholar 

  70. Nishishita T, Lin PC (2004) Angiopoietin 1, PDGF-B, and TGF-beta gene regulation in endothelial cell and smooth muscle cell interaction. J Cell Biochem 91:584–593

    Article  PubMed  CAS  Google Scholar 

  71. Satchell SC, Harper SJ, Mathieson PW (2001) Angiopoietin-1 is normally expressed by periendothelial cells. Thromb Haemost 86:1597–1598

    PubMed  CAS  Google Scholar 

  72. Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD (1996) Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Cell 87:1171–1180

    Article  PubMed  CAS  Google Scholar 

  73. Benjamin LE, Hemo I, Keshet E (1998) A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125:1591–1598

    PubMed  CAS  Google Scholar 

  74. Uemura A, Ogawa M, Hirashima M, Fujiwara T, Koyama S, Takagi H, Honda Y, Wiegand SJ, Yancopoulos GD, Nishikawa S (2002) Recombinant angiopoietin-1 restores higher-order architecture of growing blood vessels in mice in the absence of mural cells. J Clin Invest 110:1619–1628

    Article  PubMed  CAS  Google Scholar 

  75. Jain RK (2003) Molecular regulation of vessel maturation. Nat Med 9:685–693

    Article  PubMed  CAS  Google Scholar 

  76. Risau W, Hallmann R, Albrecht U (1986) Differentiation-dependent expression of proteins in brain endothelium during development of the blood-brain barrier. Dev Biol 117:537–545

    Article  PubMed  CAS  Google Scholar 

  77. Bauer H, Sonnleitner U, Lametschwandtner A, Steiner M, Adam H, Bauer HC (1995) Ontogenic expression of the erythroid-type glucose transporter (Glut 1) in the telencephalon of the mouse: correlation to the tightening of the blood–brain barrier. Brain Res Dev Brain Res 86:317–325

    Article  PubMed  CAS  Google Scholar 

  78. Saunders NR, Knott GW, Dziegielewska KM (2000) Barriers in the immature brain. Cell Mol Neurobiol 20:29–40

    Article  PubMed  CAS  Google Scholar 

  79. Arthur FE, Shivers RR, Bowman PD (1987) Astrocyte-mediated induction of tight junctions in brain capillary endothelium: an efficient in vitro model. Brain Res 433:155–159

    PubMed  CAS  Google Scholar 

  80. Risau W (1991) Induction of blood–brain barrier endothelial cell differentiation. Ann NY Acad Sci 633:405–419

    Article  PubMed  CAS  Google Scholar 

  81. Tserentsoodol N, Shin BC, Suzuki T, Takata K (1998) Colocalization of tight junction proteins, occludin and ZO-1, and glucose transporter GLUT1 in cells of the blood–ocular barrier in the mouse eye. Histochem Cell Biol 110:543–551

    Article  PubMed  CAS  Google Scholar 

  82. Russ PK, Davidson MK, Hoffman LH, Haselton FR (1998) Partial characterization of the human retinal endothelial cell tight and adherens junction complexes. Invest Ophthalmol Vis Sci 39:2479–2485

    PubMed  CAS  Google Scholar 

  83. Barber AJ, Antonetti DA (2003) Mapping the blood vessels with paracellular permeability in the retinas of diabetic rats. Invest Ophthalmol Vis Sci 44:5410–5416

    Article  PubMed  Google Scholar 

  84. Barber AJ, Antonetti DA, Gardner TW (2000) Altered expression of retinal occludin and glial fibrillary acidic protein in experimental diabetes. The Penn State Retina Research Group. Invest Ophthalmol Vis Sci 41:3561–3568

    PubMed  CAS  Google Scholar 

  85. Kevil CG, Okayama N, Trocha SD, Kalogeris TJ, Coe LL, Specian RD, Davis CP, Alexander JS (1998) Expression of zonula occludens and adherens junctional proteins in human venous and arterial endothelial cells: role of occludin in endothelial solute barriers. Microcirculation 5:197–210

    Article  PubMed  CAS  Google Scholar 

  86. Wong V, Gumbiner BM (1997) A synthetic peptide corresponding to the extracellular domain of occludin perturbs the tight junction permeability barrier. J Cell Biol 136:399–409

    Article  PubMed  CAS  Google Scholar 

  87. Antonetti DA, Barber AJ, Khin S, Lieth E, Tarbell JM, Gardner TW (1998) Vascular permeability in experimental diabetes is associated with reduced endothelial occludin content: vascular endothelial growth factor decreases occludin in retinal endothelial cells. Penn State Retina Research Group. Diabetes 47:1953–1959

    Article  PubMed  CAS  Google Scholar 

  88. Gardner TW, Lieth E, Khin SA, Barber AJ, Bonsall DJ, Lesher T, Rice K, Brennan WA Jr (1997) Astrocytes increase barrier properties and ZO-1 expression in retinal vascular endothelial cells. Invest Ophthalmol Vis Sci 38:2423–2427

    PubMed  CAS  Google Scholar 

  89. Tout S, Chan-Ling T, Hollander H, Stone J (1993) The role of Muller cells in the formation of the blood-retinal barrier. Neuroscience 55:291–301

    Article  PubMed  CAS  Google Scholar 

  90. Gariano RF, Iruela-Arispe ML, Hendrickson AE (1994) Vascular development in primate retina: comparison of laminar plexus formation in monkey and human. Invest Ophthalmol Vis Sci 35:3442–3445

    PubMed  CAS  Google Scholar 

  91. Provis JM (2001) Development of the primate retinal vasculature. Prog Retin Eye Res 20:799–821

    Article  PubMed  CAS  Google Scholar 

  92. Engerman RL, Meyer RK (1965) Development of retinal vasculature in rats. Am J Ophthalmol 60:628–641

    PubMed  CAS  Google Scholar 

  93. Heckenlively JR, Hawes NL, Friedlander M, Nusinowitz S, Hurd R, Davisson M, Chang B (2003) Mouse model of subretinal neovascularization with choroidal anastomosis. Retina 23:518–522

    Article  PubMed  Google Scholar 

  94. Trommsdorff M, Gotthardt M, Hiesberger T, Shelton J, Stockinger W, Nimpf J, Hammer RE, Richardson JA, Herz J (1999) Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2. Cell 97:689–701

    Article  PubMed  CAS  Google Scholar 

  95. Hackett SF, Wiegand S, Yancopoulos G, Campochiaro PA (2002) Angiopoietin-2 plays an important role in retinal angiogenesis. J Cell Physiol 192:182–187

    Article  PubMed  CAS  Google Scholar 

  96. Hackett SF, Ozaki H, Strauss RW, Wahlin K, Suri C, Maisonpierre P, Yancopoulos G, Campochiaro PA (2000) Angiopoietin 2 expression in the retina: upregulation during physiologic and pathologic neovascularization. J Cell Physiol 184:275–284

    Article  PubMed  CAS  Google Scholar 

  97. Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (1997) Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis. Science 277:55–60

    Article  PubMed  CAS  Google Scholar 

  98. Luhmann UF, Lin J, Acar N, Lammel S, Feil S, Grimm C, Seeliger MW, Hammes HP, Berger W (2005) Role of the Norrie disease pseudoglioma gene in sprouting angiogenesis during development of the retinal vasculature. Invest Ophthalmol Vis Sci 46:3372–3382

    Article  PubMed  Google Scholar 

  99. Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J (2004) Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell 116:883–895

    Article  PubMed  CAS  Google Scholar 

  100. Ohlmann A, Scholz M, Goldwich A, Chauhan BK, Hudl K, Ohlmann AV, Zrenner E, Berger W, Cvekl A, Seeliger MW, Tamm ER (2005) Ectopic norrin induces growth of ocular capillaries and restores normal retinal angiogenesis in Norrie disease mutant mice. J Neurosci 25:1701–1710

    Article  PubMed  CAS  Google Scholar 

  101. Chen ZY, Battinelli EM, Fielder A, Bundey S, Sims K, Breakefield XO, Craig IW (1993) A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy. Nat Genet 5:180–183

    Article  PubMed  CAS  Google Scholar 

  102. Toomes C, Downey LM, Bottomley HM, Scott S, Woodruff G, Trembath RC, Inglehearn CF (2004) Identification of a fourth locus (EVR4) for familial exudative vitreoretinopathy (FEVR). Mol Vis 10:37–42

    PubMed  CAS  Google Scholar 

  103. Enyedi LB, de Juan E Jr, Gaitan A (1991) Ultrastructural study of Norrie’s disease. Am J Ophthalmol 111:439–445

    PubMed  CAS  Google Scholar 

  104. Toomes C, Bottomley HM, Jackson RM, Towns KV, Scott S, Mackey DA, Craig JE, Jiang L, Yang Z, Trembath R, Woodruff G, Gregory-Evans CY, Gregory-Evans K, Parker MJ, Black GC, Downey LM, Zhang K, Inglehearn CF (2004) Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet 74:721–730

    Article  PubMed  CAS  Google Scholar 

  105. Kato M, Patel MS, Levasseur R, Lobov I, Chang BH, Glass DA, Hartmann C, Li L, Hwang TH, Brayton CF, Lang RA, Karsenty G, Chan L (2002) Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol 157:303–314

    Article  PubMed  CAS  Google Scholar 

  106. Goldberg MF (1997) Persistent fetal vasculature (PFV): an integrated interpretation of signs and symptoms associated with persistent hyperplastic primary vitreous (PHPV). LIV Edward Jackson Memorial Lecture. Am J Ophthalmol 124:587–626

    PubMed  CAS  Google Scholar 

  107. Lang RA, Bishop JM (1993) Macrophages are required for cell death and tissue remodeling in the developing mouse eye. Cell 74:453–462

    Article  PubMed  CAS  Google Scholar 

  108. Diez-Roux G, Lang RA (1997) Macrophages induce apoptosis in normal cells in vivo. Development 124:3633–3638

    PubMed  CAS  Google Scholar 

  109. Lobov IB, Rao S, Carroll TJ, Vallance JE, Ito M, Ondr JK, Kurup S, Glass DA, Patel MS, Shu W, Morrisey EE, McMahon AP, Karsenty G, Lang RA (2005) WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature 437:417–421

    Article  PubMed  CAS  Google Scholar 

  110. Richter M, Gottanka J, May CA, Welge-Lussen U, Berger W, Lutjen-Drecoll E (1998) Retinal vasculature changes in Norrie disease mice. Invest Ophthalmol Vis Sci 39:2450–2457

    PubMed  CAS  Google Scholar 

  111. Chang B, Smith RS, Peters M, Savinova OV, Hawes NL, Zabaleta A, Nusinowitz S, Martin JE, Davisson ML, Cepko CL, Hogan BL, John SW (2001) Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure. BMC Genet 2:18

    Article  PubMed  CAS  Google Scholar 

  112. Rousseau B, Larrieu-Lahargue F, Bikfalvi A, Javerzat S (2003) Involvement of fibroblast growth factors in choroidal angiogenesis and retinal vascularization. Exp Eye Res 77:147–156

    Article  PubMed  CAS  Google Scholar 

  113. Fukai N, Eklund L, Marneros AG, Oh SP, Keene DR, Tamarkin L, Niemela M, Ilves M, Li E, Pihlajaniemi T, Olsen BR (2002) Lack of collagen XVIII/endostatin results in eye abnormalities. EMBO J 21:1535–1544

    Article  PubMed  CAS  Google Scholar 

  114. Ishida S, Usui T, Yamashiro K, Kaji Y, Amano S, Ogura Y, Hida T, Oguchi Y, Ambati J, Miller JW, Gragoudas ES, Ng YS, D’Amore PA, Shima DT, Adamis AP (2003) VEGF164-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J Exp Med 198:483–489

    Article  PubMed  CAS  Google Scholar 

  115. Yoshida S, Yoshida A, Ishibashi T, Elner SG, Elner VM (2003) Role of MCP-1 and MIP-1alpha in retinal neovascularization during postischemic inflammation in a mouse model of retinal neovascularization. J Leukoc Biol 73:137–144

    Article  PubMed  CAS  Google Scholar 

  116. Alva JA, Iruela-Arispe ML (2004) Notch signaling in vascular morphogenesis. Curr Opin Hematol 11:278–283

    Article  PubMed  CAS  Google Scholar 

  117. Bicknell R, Harris AL (2004) Novel angiogenic signaling pathways and vascular targets. Annu Rev Pharmacol Toxicol 44:219–238

    Article  PubMed  CAS  Google Scholar 

  118. Shibuya M, Claesson-Welsh L (2006) Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis. Exp Cell Res 312:549–560

    Article  PubMed  CAS  Google Scholar 

  119. Thurston G (2003) Role of angiopoietins and Tie receptor tyrosine kinases in angiogenesis and lymphangiogenesis. Cell Tissue Res 314:61–68

    Article  PubMed  CAS  Google Scholar 

  120. Bainbridge JW, Mistry A, De Alwis M, Paleolog E, Baker A, Thrasher AJ, Ali RR (2002) Inhibition of retinal neovascularisation by gene transfer of soluble VEGF receptor sFlt-1. Gene Ther 9:320–326

    Article  PubMed  CAS  Google Scholar 

  121. McLeod DS, Taomoto M, Cao J, Zhu Z, Witte L, Lutty GA (2002) Localization of VEGF receptor-2 (KDR/Flk-1) and effects of blocking it in oxygen-induced retinopathy. Invest Ophthalmol Vis Sci 43:474–482

    PubMed  Google Scholar 

  122. Campochiaro PA (2006) Ocular versus extraocular neovascularization: mirror images or vague resemblances. Invest Ophthalmol Vis Sci 47:462–474

    Article  PubMed  Google Scholar 

  123. Shen J, Yang X, Xiao WH, Hackett SF, Sato Y, Campochiaro PA (2006) Vasohibin is up-regulated by VEGF in the retina and suppresses VEGF receptor 2 and retinal neovascularization. FASEB J 20:723–725

    PubMed  CAS  Google Scholar 

  124. Aronoff R, Petersen CC (2006) Controlled and localized genetic manipulation in the brain. J Cell Mol Med 10:333–352

    PubMed  Google Scholar 

Download references

Acknowledgements

The author thanks Joanne Taylor and Christiana Ruhrberg for critical reading of the manuscript. The work was made possible by funding from the Lowy Medical Research Institute LTD and the Medical Research Council.

Author information

Authors and Affiliations

  1. UCL Institute of Ophthalmology, 11-43 Bath Street, London, EC1V 9EL, UK

    Marcus Fruttiger

Authors
  1. Marcus Fruttiger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Marcus Fruttiger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fruttiger, M. Development of the retinal vasculature. Angiogenesis 10, 77–88 (2007). https://doi.org/10.1007/s10456-007-9065-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10456-007-9065-1

Keywords

Search

Navigation