Skip to main content
SpringerLink
Log in
Book cover

Retinal and Choroidal Angiogenesis pp 221–240Cite as

Adenosine in Retinal Vasculogenesis and Angiogenesis in Oxygen-Induced Retinopathy

  • Chapter

  • 723 Accesses

Abstract

Adenosine is a ubiquitous molecule produced predominantly by catabolism of adenosine triphosphate. Levels of this nucleoside increase dramatically with ischemia and elevated tissue activity. Adenosine induces angiogenesis in tumors and wound healing and upregulates VEGF production in several cell types, including endothelial cells. The source of adenosine in most tissues appears to be the ectoenzyme 5’ nucleotidase, which is hypoxia inducible. 5’ nucleotidase expression is prominent during retinal vascular development in the innermost processes of Muller cells, and levels of its product, adenosine, are high in inner retina during retinal vascular development in postnatal dog. One of the adenosine receptors, A2A, is present on angioblasts and on endothelial cells of formed blood vessels during canine retinal vascular development. These observations suggest that adenosine is important in retinal vascular development.

Oxygen-induced retinopathy (OIR) is a model for human retinopathy of prematurity (ROP). OIR is induced by exposure of the developing retina to high oxygen. Vascular development is halted, and over 60% of the retinal vasculature is lost during this stage, which is called vaso-obliteration. Expression of 5’ nucleotidase is dramatically reduced during vaso-obliteration, resulting in a sharp decline in adenosine. When animals are returned to room air, the retina is hypoxic because of the lack of blood vessels and increased oxygen consumption due to neuronal development. At this time, the vasoproliferative stage of OIR begins, and 5’ nucleotidase activity and adenosine levels become elevated well beyond normal. A2A-positive endothelial cell proliferation is also elevated compared to control animals. Florid preretinal neovascularization occurs and is characterized by high levels of adenosine and A2A receptors. Therefore, adenosine and its A2A receptor appear to be important in canine OIR. This has also been demonstrated in the mouse model of OIR. Systemically administered antagonists of the adenosine A2B receptor significantly reduced retinal neovascularization in mice,1 as did cleavage of A2B by a ribozyme.2 These studies suggest that adenosine and its receptors are important in retinal vascular development and may be a therapeutic target in OIR.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. R. P. Mino, P. E. Spoerri, S. Caballero, D. Player, L. Belardinelli, I. Biaggioni, and M. B. Grant, Adenosine receptor antagonists and retinal neovascularization in vivo, Invest. Ophthalmol. Vis. Sci. 42 (13), 3320-3324 (2001).

    PubMed  CAS  Google Scholar 

  2. A. Afzal, L. Shaw, S. Caballero, P. Spoerri, A. Lewin, D. Zeng, L. Belardinelli, and M. B. Grant, Reduction in preretinal neovascularization by ribozymes that cleave the A2b adenosine receptor mRNA, Circ. Res. 93, 500-506 (2003).

    Article  PubMed  CAS  Google Scholar 

  3. J. Linden, Molecular approach to adenosine receptors: receptor-mediated mechanisms of tissue protection, Annu. Rev. Pharmacol. Toxicol. 41, 775-787 (2001).

    Article  PubMed  CAS  Google Scholar 

  4. S. A. Rivkees, Z. Zhao, G. Porter, and C. Turner, Influences of adenosine on the fetus and newborn, Mol. Genet. Metab. 74 (1-2), 160-171 (2001).

    Article  PubMed  CAS  Google Scholar 

  5. G. Schopf, H. Rumpold, and M. M. Muller, Alterations of purine salvage pathways during differentiation of rat heart myoblasts toward myocytes, Biochimica et Biophysica Acta 884, 319-325 (1986).

    PubMed  CAS  Google Scholar 

  6. N. Braun, C. Lenz, F. Gillardon, M. Zimmerman, and H. Zimmerman, Focal cerebral ischemia enhances glial expression of ecto-5’-nucleotidase, Brain Res. 766, 213-226 (1997).

    Article  PubMed  CAS  Google Scholar 

  7. M. Kitakaze, M. Hori, and T. Kamada, Role of adenosine and its interaction with alpha adrenoceptor activity in ischaemic and reperfusion injury of the myocardium, Cardiovascular Res. 27, 18-27 (1993).

    CAS  Google Scholar 

  8. K. Synnestvedt, G. T. Furuta, K. M. Comerford, N. Louis, J. Karhausen, H. K. Eltzschig, K. R. Hansen, L. F. Thompson, and S. P. Colgan, Ecto-5’-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia, J. Clin. Invest. 110 (7), 993-1002 (2002).

    Article  PubMed  CAS  Google Scholar 

  9. M. Freissmuth, W. Schutz, and M. E. Linder, Interactions of the bovine brain A1-adenosine receptor with recombinant G protein a-subunits. Selectivity for rGioa - 3, J. Biol. Chem. 266, 17778-17783 (1991).

    PubMed  CAS  Google Scholar 

  10. C. Blazynski, Adenosine A1 receptor-mediated inhibition of adenylate cyclase in rabbit retina, J. Neuroscience 7, 2522-2528 (1987).

    CAS  Google Scholar 

  11. W. Abebe and S. J. Mustafa, A1 adenosine receptor mediated Ins(1,4,5)P3 generation in allergic rabbit airway smooth muscle, Am. J. Physiol. 275, L990-L997 (1998).

    Google Scholar 

  12. B. T. Liang, Direct preconditioning of cardiac ventricular myocytes via adensoine A1 and KATP channel, Am. J.Physiol. 271, H1769-H1777 (1996).

    PubMed  CAS  Google Scholar 

  13. R. B. Marala and S. J. Mustafa, Immunological characterization of adenosine A2a receptors in human and porcine cardiovascular tissue, J. Pharmacol. Exp. Ther. 286, 1051-1057 (1998).

    PubMed  CAS  Google Scholar 

  14. V. Stefanovic, P. Vlahovic, V. Savic, and R. Ardaillou, Adenosine stimulates 5’-nucleotidase activity in rat mesangial cells via A2 receptor, FEBS Lett. 331, 96-100 (1993).

    Article  PubMed  CAS  Google Scholar 

  15. S. N. Li and P. T. Wong, The adenosine receptor agonist, APNEA, increases Ca+ + influx into rat cortical synaptosomes through N-type channels associated with A2a receptors, Neurochem. Res. 25, 457-459 (2000).

    Article  PubMed  CAS  Google Scholar 

  16. T. M. Palmer, T. W. Gettys, and G. L. Stiles, Differentail interaction with and regulation of multiple G-proteins by the rat A3 adenossne receptor, J. Biol. Chem. 270, 16895-16902 (1995).

    Article  PubMed  CAS  Google Scholar 

  17. M. P. Abbracchio, R. Brambilla, S. Ceruti, H. O. Kim, D. K. von Lubitz, and K. A. Jacobsen, G protein-dependent activation of phospholipase C by adensoine A3 receptors in rat brain, Mol. Pharmacol. 48, 1038-1045 (1995).

    PubMed  CAS  Google Scholar 

  18. Z. Zhao, C. E. Francis, and K. Ravid, An A3-subtype receptor is highly expressed in rat smooth muscle cells: its role in attenuating adensoine-induced increase in camp, Microvasc. Res. 54, 243-252 (1997).

    Article  PubMed  CAS  Google Scholar 

  19. Z. Zhao, K. Makaritsis, C. E. Francis, H. Gavris, and K. Ravid, A role for the A3 adensoine receptor in determining tissue levels of cAMP and blood pressure: studies in knockout mice, Biochem. Biophys. Acta 1500, 280-290 (2000).

    PubMed  CAS  Google Scholar 

  20. R. Berne, R. Knabb, S. W. Ely, and R. Rubio, Adenosine in the local regulation of blood flow: a brief overview, Federation Proc. 42, 3136-3142 (1983).

    CAS  Google Scholar 

  21. J. W. Phillis, Adenosine in the control of cerebral circulation, Cerebrovascular and Brain Metabolism Reviews 1, 26-54 (1989).

    PubMed  CAS  Google Scholar 

  22. H. Winn, S. Morii, and R. Berne, The role of adenosine in autoregulation of cerebral blood flow, Annals Biomed. Engineering 13, 321-328 (1985).

    Article  CAS  Google Scholar 

  23. R. Tabrizchi and S. Bedi, Pharmacology of adenosine receptors in the vasculature, Pharmacol. Ther. 91 (2), 133-147 (2001).

    Article  PubMed  CAS  Google Scholar 

  24. H. A. Olanrewaju and S. J. Mustafa, Adenosine A(2A) and A(2B) receptors mediated nitric oxide production in coronary artery endothelial cells, Gen. Pharmacol. 35 (3), 171-177 (2000).

    PubMed  CAS  Google Scholar 

  25. J. W. Dusseau and P. M. Hutchins, Hypoxia-induced angiogenesis in chick chorioallantoic membranes: a role for adenosine, Respir. Physiol. 71, 33-44 (1988).

    Article  PubMed  CAS  Google Scholar 

  26. C. J. Meininger, M. E. Schelling, and H. J. Granger, Adenosine and hypoxia stimulate proliferation and migration of endothelial cells, Am. J. Physiol. 255, H554-H562 (1988).

    PubMed  CAS  Google Scholar 

  27. E. Teuscher and V. Weidlich, Adenosine nucleotides, adenosine and adenine as angiogenesis factors, Biomed. Biochim. Acta. 44, 493-495 (1985).

    PubMed  CAS  Google Scholar 

  28. G. A. Lutty, M. K. Mathews, C. Merges, and D. S. McLeod, Adenosine stimulates canine retinal microvascular endothelial cell migration and tube formation, Curr. Eye Res. 17 (6), 594-607 (1998).

    PubMed  CAS  Google Scholar 

  29. H. A. Olanrewaju, W. Qin, I. Feoktistov, J. L. Scemama, and S. J. Mustafa, Adenosine A(2A) and A(2B) receptors in cultured human and porcine coronary artery endothelial cells, Am. J. Physiol. Heart Circ. Physiol. 279 (2), H650-H656 (2000).

    PubMed  CAS  Google Scholar 

  30. I. Feoktistov, A. E. Goldstein, S. Ryzhov, D. Zeng, L. Belardinelli, T. Voyno-Yasenetskaya, and I. Biaggioni, Differential expression of adenosine receptors in human endothelial cells: role of A2B receptors in angiogenic factor regulation, Circ. Res. 90 (5), 531-538 (2002).

    Article  PubMed  CAS  Google Scholar 

  31. R. K. Dubey, D. G. Gillespie, and E. K. Jackson, A(2B) adenosine receptors stimulate growth of porcine and rat arterial endothelial cells, Hypertension 39 (2 Pt 2), 530-535 (2002).

    Article  PubMed  CAS  Google Scholar 

  32. M. B. Grant, M. I. Davis, S. Caballero, I. Feoktistov, I. Biaggioni, and L. Belardinelli, Proliferation, migration, and ERK activation in human retinal endothelial cells through A(2B) adenosine receptor stimulation, Invest. Ophthalmol. Vis. Sci. 42 (9), 2068-2073 (2001).

    PubMed  CAS  Google Scholar 

  33. A. Desai, C. Victor-Vega, S. Gadangi, M. C. Montesinos, C. C. Chu, and B. N. Cronstein, Adenosine A2A receptor stimulation increases angiogenesis by down-regulating production of the antiangiogenic matrix protein thrombospondin 1, Mol. Pharmacol. 67 (5), 1406-1413 (2005).

    Article  PubMed  CAS  Google Scholar 

  34. G. W. Kreutzberg and S. T. Hussain, Cytochemical heterogeneity of the glial plasma membrane: 5’-nucleotidase in retinal Müller cells, J. Neurocytol. 11, 53-64 (1982).

    Article  PubMed  CAS  Google Scholar 

  35. N. Braun, P. Brendel, and H. Zimmerman, Distribution of 5’-nucleotidase in the developing mouse retina, Brain Res. 88, 79-86 (1995).

    Article  CAS  Google Scholar 

  36. G. A. Lutty, C. Merges, and D. S. McLeod, 5’ nucleotidase and adenosine during retinal vasculogenesis and oxygen- induced retinopathy, Invest. Ophthalmol. Vis. Sci. 41 (1), 218-229 (2000).

    PubMed  CAS  Google Scholar 

  37. C. Blazynski and M. T. Perez, Neuroregulatory functions of adenosine in the retina, Prog. Retinal Res. 11, 293-332 (1992).

    Article  Google Scholar 

  38. K. M. Braas, M. A. Zarbin, and S. H. Snyder, Endogenous adenosine and adenosine receptors localized to ganglion cells of the retina, Proc. Natl. Acad. Sci., USA 84, 3906-3910 (1987).

    Article  PubMed  CAS  Google Scholar 

  39. C. Blazynski, J. L. Mosinger, and A. I. Cohen, Comparison of adenosine uptake and endogenous adenosine-containing cells in mammalian retina, Vis. Neurosci. 2, 109-116 (1989).

    PubMed  CAS  Google Scholar 

  40. P. Ostwald, S. S. Park, A. Y. Toledando, and S. Roth, Adenosine receptor blockade and nitric oxide synthase inhibition in the retina: Impact upon post-ischemic hyperemia and the electroretinogram, Vis. Res. 37, 3453-3461 (1997).

    Article  PubMed  CAS  Google Scholar 

  41. J. M. Gidday and T. S. Park, Adenosine-mediated autoregulation of retinal arteriolar tone in the piglet, Invest. Ophthalmol. Vis. Sci. 34, 2713-2719 (1993).

    PubMed  CAS  Google Scholar 

  42. J. M. Gidday and T. S. Park, Microcirculatory responses to adenosine in the newborn pig, Pediatr. Res. 33, 620-627 (1993).

    Article  PubMed  CAS  Google Scholar 

  43. S. Roth, S. S. Park, C. W. Sikorski, J. Osinski, R. Chan, and K. Loomis, Concentrations of adenosine and its metabolites in the rat retina/choroid during reperfusion after ischemia, Curr. Eye Res. 16, 875-885 (1997).

    Article  PubMed  CAS  Google Scholar 

  44. S. Roth, P. S. Rosenbaum, J. Osinski, S. S. Park, A. Y. Toledano, B. Li, and A. A. Moshfeghi, Ischemia induces significant changes in purine nucleoside concentration in the retina-choroid in rats, Exp. Eye Res. 65, 771-779 (1997).

    Article  PubMed  CAS  Google Scholar 

  45. A. K. Larsen and N. N. Osbourne, Involvement of adenosine in retinal ischemia. Studies on rat, Invest. Ophthalmol. Vis. Sci. 37, 2603-2611 (1996).

    PubMed  CAS  Google Scholar 

  46. B. Li, P. S. Rosenbaum, N. M. Jennings, K. A. Maxwell, and S. Roth, Differential roles of adenosine receptor subtypes in retinal ischemia-reperfusion injury in the rat, Exp. Eye Res. 68, 9-17 (1999).

    Article  PubMed  CAS  Google Scholar 

  47. B. Li and S. Roth, Retinal preconditioning in the rat: requirement for adenosine and repetitive induction, Invest. Ophthalmol. Vis. Sci. 40, 1200-1216 (1999).

    PubMed  CAS  Google Scholar 

  48. G. J. Ghiardi, J. M. Gidday, and S. Roth, The purine nucleoside adenosine in retinal ischemia-reperfusion injury, Vision Res. 39, 2519-2535 (1999).

    Article  PubMed  CAS  Google Scholar 

  49. S. Fischer, H. S. Sharma, G. F. Kaliczek, and W. Schaper, Expression of vascular permeability factor/vascular endothelial growth factor in pig cerebral microvascular endothelial cells and its upregulation by adenosine, Mol. Brain Res. 28, 141-148 (1995).

    Article  PubMed  CAS  Google Scholar 

  50. H. Takagi, G. L. King, G. S. Robinson, N. Ferrara, and L. P. Aiello, Adenosine mediates hypoxic induction of vascular endothelial growth factor in retinal pericytes and endothelial cells, Invest. Ophthalmol. Vis. Sci. 37, 2165-2176 (1996).

    PubMed  CAS  Google Scholar 

  51. H. Takagi, G. L. King, N. Ferrara, and L. P. Aiello, Hypoxia regulates vascular endothelial growth factor receptor KDR/Flk gene expression through adenosine A2 receptors in retinal capillary endothelial cells, Invest. Ophthalmol. Vis. Sci. 37, 1311-1321 (1996).

    PubMed  CAS  Google Scholar 

  52. M. B. Grant, R. W. Tarnuzzer, S. Cabalerro, M. J. Ozeck, M. I. Davis, P. E. Spoerri, I. Feoktistov, I. Biaggioni, J. C. Shryock, and L. Belardinelli, Adenosine receptor activation induces vascular endothelial growth factor in human endothelial cells, Circ. Res. 85, 699-706 (1999).

    PubMed  CAS  Google Scholar 

  53. R. W. Flower, D. S. McLeod, G. A. Lutty, B. Goldberg, and S. D. Wajer, Postnatal retinal vascular development of the puppy, Invest. Ophthal. Vis. Sci. 26, 957-968 (1985).

    PubMed  CAS  Google Scholar 

  54. D. S. McLeod, R. Brownstein, and G. A. Lutty, Vaso-obliteration in the canine model of oxygen-induced retinopathy, Invest. Ophthalmol. Vis. Sci. 37, 300-311 (1996).

    PubMed  CAS  Google Scholar 

  55. D. S. McLeod and G. A. Lutty, Menadione-dependent alpha glycerophosphate and succinate dehydrogenases in the developing canine retina, Curr. Eye Res. 14, 819-826 (1995).

    Article  PubMed  CAS  Google Scholar 

  56. D. S. McLeod, G. A. Lutty, S. D. Wajer, and R. W. Flower, Visualization of a developing vasculature, Microvasc. Res. 33, 257-269 (1987).

    Article  PubMed  CAS  Google Scholar 

  57. T. Chan-Ling, D. S. McLeod, S. Hughes, L. Baxter, Y. Chu, T. Hasegawa, and G. A. Lutty, Astrocyte-endothelial cell relationships during human retinal vascular development, Invest. Ophthalmol. Vis. Sci. 45, 2020-2032 (2004).

    Article  PubMed  Google Scholar 

  58. M. Taomoto, D. S. McLeod, C. Merges, and G. A. Lutty, Localization of adenosine A2a receptor in retinal development and oxygen-induced retinopathy, Invest. Ophthalmol. Vis. Sci. 41 (1), 230-243 (2000).

    PubMed  CAS  Google Scholar 

  59. A. Van Waarde, M. E. Stromski, G. Thulin, K. M. Guadio, M. Kashgarian, R. G. Shulman, and N. J. Siegel, Protection of the kidney against ischemic injury by inhibition of 5’-nucleotidase, Am. J. Physiol. 256, F298-F305 (1989).

    PubMed  Google Scholar 

  60. G. A. Gole, Animal models of retinopathy of prematurity, in: Retinopathy of prematurity, edited by W. A. Silverman and J. T. Flynn (Blackwell Scientific Publications, Boston, 1985) pp. 53-95.

    Google Scholar 

  61. X. Reynaud and C. K. Dorey, Extraretinal neovascularization induced by hypoxic episodes in the neonatal rat, Invest. Ophthalmol. Vis. Sci. 35, 3169-3177 (1994).

    PubMed  CAS  Google Scholar 

  62. J. S. Penn, B. L. Tolman, and M. M. Henry, Oxygen-induced retinopathy in the rat: relationship of retinal nonperfusion to subsequent neovascularization, Invest. Ophthalmol. Vis. Sci. 35, 3429-3435 (1994).

    PubMed  CAS  Google Scholar 

  63. D. S. McLeod, S. A. D’Anna, and G. A. Lutty, Clinical and histopathologic features of canine oxygen-induced proliferative retinopathy, Invest. Ophthalmol. Vis. Sci. 39 (10), 1918-1932 (1998).

    PubMed  CAS  Google Scholar 

  64. L. E. H. Smith, E. Wesolowski, A. McLellan, S. K. Kostyk, R. D. D’Amato, R. Sullivan R, and P. A. D’Amore, Oxygen-induced retinopathy in the mouse, Invest. Ophthalmol. Vis. Sci. 35 (1), 101-111 (1994).

    PubMed  CAS  Google Scholar 

  65. T. Chan-Ling, S. Tout, H. Holländer, and J. Stone, Vascular changes and their mechanisms in the feline model of retinopathy of prematurity, Invest. Ophthalmol. Vis. Sci. 33 (7), 2128-2147 (1992).

    PubMed  CAS  Google Scholar 

  66. N. Ashton, B. Ward, and G. Serpell, Effect of oxygen on developing retinal vessels with particular reference to the problem of retrolental fibroplasias, Br. J. Ophthalmol. 38, 397-428 (1954).

    Article  PubMed  CAS  Google Scholar 

  67. T. Chan-Ling, B. Gock, and J. Stone, The effect of oxygen on vasoformative cell division. Evidence that ‘physiological hypoxia’ is the stimulus for normal retinal vasculogenesis, Invest. Ophthalmol. Vis. Sci. 36, 1201-1214 (1995).

    PubMed  CAS  Google Scholar 

  68. A. Patz, Oxygen studies in retrolental fibroplasia:IV clinical and experimental observations, Am. J. Ophthalmol. 38, 291-307 (1954).

    PubMed  CAS  Google Scholar 

  69. M. Kitakaze, M. Hori, S. Takashima, K. Iwai, H. Sato, M. Inoue, A. Kitabatake, and T. Kamada, Superoxide dismutase enhances ischemia- induced reactive hyperemic flow and adenosine release in dogs, Circ. Res. 71, 558-566 (1992).

    PubMed  CAS  Google Scholar 

  70. M. Kitakaze, M. Hori, T. Morioka, S. Takashima, T. Minamino, H. Sato, M. Inoue, and T. Kamada, Attenuation of ecto-5’-nucleotidase activity and adenosine release in activated human polymorphonuclear leukocytes, Circ. Res. 73, 524-533 (1993).

    PubMed  CAS  Google Scholar 

  71. Y. F. Chen, P. L. Li, and A. P. Zou, Oxidative stress enhances the production and actions of adenosine in the kidney, Am. J. Physiol. Regulatory Integrative Comp. Physiol. 281, R1808-R1816 (2001).

    CAS  Google Scholar 

  72. D. S. McLeod, S. N. Crone, and G. A. Lutty, Vasoproliferation in the neonatal dog model of oxygen-induced retinopathy, Invest. Ophthalmol. Vis. Sci. 37 (7), 1322-1333 (1996).

    PubMed  CAS  Google Scholar 

  73. S. E. Brooks, X. Gu, S. Samuel, D. M. Marcus, M. Bartoli, P. L. Huang, and R. B. Caldwell, Reduced severity of oxygen-induced retinopathy in eNOS-deficient mice, Invest. Ophthalmol. Vis. Sci. 42, 222-228 (2001).

    PubMed  CAS  Google Scholar 

  74. C. D. Lewis, S. M. Hourani, C. J. Long, and M. G. Collis, Characterization of adenosine receptors in the rat isolated aorta, Gen. Pharmac. 25, 1381-1387 (1994).

    CAS  Google Scholar 

  75. S. M. Poucher, J. R. Keddie, R. Brooks, G. R. Shaw, and D. McKillup, Pharmacodynamics of ZM 241385, a potent A2a adenosine antagonist, after enteric administration in rat, cat and dog, J. Pharm. Pharmacol. 48, 601-606 (1996).

    PubMed  CAS  Google Scholar 

  76. L. Sobrevia, D. L. Yudilevich, and G. E. Mann, Activation of A2-purinoceptors by adenosine stimulates L-arginine transport (system y+) and nitric oxide synthesis in fetal human endothelial cells, J. Physiol. 499, 135-140 (1997).

    PubMed  CAS  Google Scholar 

  77. S. J. Mustafa and W. Abebe, Coronary vasodilation by adenosine-receptor subtypes and mechanism of action, Drug Development Res. 39, 308-313 (1996).

    Article  CAS  Google Scholar 

  78. D. S. McLeod, M. Taomoto, J. Cao, Z. Zhu, L. Witte, and G. A. Lutty, Localization of VEGF receptor-2 (KDR/FLK-1) and effects of blocking it in oxygen-induced retinopathy, Invest. Ophthalmol. Vis. Sci. 43, 474-482 (2002).

    PubMed  Google Scholar 

  79. R. R. Morrison, M. A. Talukder, C. Ledent, and S. J. Mustafa, Cardiac effects of adenosine in A(2A) receptor knockout hearts: uncovering A(2B) receptors, Am. J. Physiol. Heart Circ. Physiol. 282 (2), H437-H444 (2002).

    PubMed  CAS  Google Scholar 

  80. J. L. Moreau and G. Huber, Central adenosine A(2A) receptors: an overview, Brain Res. Brain Res. Rev. 31, 65-82 (1999).

    Article  PubMed  CAS  Google Scholar 

  81. A. Afzal, L. C. Shaw, S. Caballero, E. A. Ellis, and M. B. Grant, The development of hammerhead ribozymes that specifically cleave the A2B receptor mRNA, Invest. Ophthalmol. Vis. Sci. 43, ARVO abstract #3711 (2002).

    Google Scholar 

  82. J. A. Forsythe, B. Jiang, N. V. Iyer, F. Agani, S. W. Leung, R. D. Koos, and G. L. Semenza, Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1, Mol. Cell. Biol. 16, 4604-4613 (1996).

    PubMed  CAS  Google Scholar 

  83. P. H. Maxwell and P. J. Ratcliffe, Oxygen sensors and angiogenesis, Seminars in Cell & Developmental Biology 13 (1), 29-37 (2002).

    Article  CAS  Google Scholar 

  84. C. Michiels, E. Minet, G. Michel, D. Mottet, J. Piret, and M. Raes, HIF-1 and AP-1 cooperate to increase gene expression in hypoxia: role of MAP kinases, IUBMB Life 52, 49-53 (2001).

    Article  PubMed  CAS  Google Scholar 

  85. G. A. Lutty and D. S. McLeod, Retinal vascular development and oxygen-induced retinopathy: a role for adenosine, Prog. Ret. Eye Res. 22, 95-111 (2003).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Wilmer Ophthalmological Institute,Johns Hopkins Hospital, Baltimore, Maryland

    Gerard A. Lutty PhD & D. Scott McLeod

Authors
  1. Gerard A. Lutty PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Scott McLeod
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Vanderbilt University School of Medicine, Nashville, TN, U.S.A

    J.S. Penn

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Lutty, G.A., McLeod, D.S. (2008). Adenosine in Retinal Vasculogenesis and Angiogenesis in Oxygen-Induced Retinopathy. In: Penn, J. (eds) Retinal and Choroidal Angiogenesis. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6780-8_12

Download citation

Publish with us

Policies and ethics

Search

Navigation