Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 13 June 1997:
Vol. 276. no. 5319, pp. 1706 - 1709
DOI: 10.1126/science.276.5319.1706
Prev | Table of Contents | Next

Reports

Essential Role of Growth Hormone in Ischemia-Induced Retinal Neovascularization

Lois E. H. Smith, * John J. Kopchick, Wen Chen, Joanne Knapp, Fumi Kinose, Douglas Daley, Eliot Foley, Roy G. Smith, James M. Schaeffer

Retinal neovascularization is the major cause of untreatable blindness. The role of growth hormone (GH) in ischemia-associated retinal neovascularization was studied in transgenic mice expressing a GH antagonist gene and in normal mice given an inhibitor of GH secretion (MK678). Retinal neovascularization was inhibited in these mice in inverse proportion to serum levels of GH and a downstream effector, insulin-like growth factor-I (IGF-I). Inhibition was reversed with exogenous IGF-I administration. GH inhibition did not diminish hypoxia-stimulated retinal vascular endothelial growth factor (VEGF) or VEGF receptor expression. These data suggest that systemic inhibition of GH or IGF-I, or both, may have therapeutic potential in preventing some forms of retinopathy.

L. E. H. Smith, F. Kinose, D. Daley, E. Foley, Department of Ophthalmology, Harvard Medical School and Children's Hospital, Boston, MA 02115, USA.
J. J. Kopchick, W. Chen, J. Knapp, Edison Biotechnology Institute, Ohio University, Athens, OH 45701, USA.
R. G. Smith and J. M. Schaeffer, Merck Research Laboratories, Rahway, NJ 07065, USA.
*   To whom correspondence should be addressed. E-mail: smith_lo{at}a1.tch.harvard.edu

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Peptide Hormone Regulation of Angiogenesis.
C. Clapp, S. Thebault, M. C. Jeziorski, and G. Martinez De La Escalera (2009)
Physiol Rev 89, 1177-1215
   Abstract »    Full Text »    PDF »
FAK and p38-MAP Kinase-Dependent Activation of Apoptosis and Caspase-3 in Retinal Endothelial Cells by {alpha}1(IV)NC1.
C. S. Boosani, N. Nalabothula, V. Munugalavadla, D. Cosgrove, V. G. Keshamoun, N. Sheibani, and A. Sudhakar (2009)
Invest. Ophthalmol. Vis. Sci. 50, 4567-4575
   Abstract »    Full Text »    PDF »
Autocrine Human Growth Hormone Promotes Tumor Angiogenesis in Mammary Carcinoma.
S. E. Brunet-Dunand, C. Vouyovitch, S. Araneda, V. Pandey, L. J.-P. Vidal, C. Print, H. C. Mertani, P. E. Lobie, and J. K. Perry (2009)
Endocrinology 150, 1341-1352
   Abstract »    Full Text »    PDF »
Through The Eyes of a Child: Understanding Retinopathy through ROP The Friedenwald Lecture.
L. E. H. Smith (2008)
Invest. Ophthalmol. Vis. Sci. 49, 5177-5182
   Full Text »    PDF »
A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes: Data from the Diabetes Control and Complications Trial.
E. S. Kilpatrick, A. S. Rigby, and S. L. Atkin (2008)
Diabetes Care 31, 2198-2202
   Abstract »    Full Text »    PDF »
Growth hormone excess and the development of growth hormone receptor antagonists.
C. E. Higham and P. J. Trainer (2008)
Exp Physiol 93, 1157-1169
   Abstract »    Full Text »    PDF »
Effect of Intravitreal Administration of Somatostatin and sst2 Analogs on AMPA-Induced Neurotoxicity in Rat Retina.
F. Kiagiadaki and K. Thermos (2008)
Invest. Ophthalmol. Vis. Sci. 49, 3080-3089
   Abstract »    Full Text »    PDF »
The Role of Nitric Oxide and cGMP in Somatostatin's Protection against Retinal Ischemia.
N. Mastrodimou, F. Kiagiadaki, and K. Thermos (2008)
Invest. Ophthalmol. Vis. Sci. 49, 342-349
   Abstract »    Full Text »    PDF »
Interleukin-18 regulates pathological intraocular neovascularization.
H. Qiao, K.-H. Sonoda, Y. Ikeda, T. Yoshimura, K. Hijioka, Y.-J. Jo, Y. Sassa, C. Tsutsumi-Miyahara, Y. Hata, S. Akira, et al. (2007)
J. Leukoc. Biol. 81, 1012-1021
   Abstract »    Full Text »    PDF »
Triamcinolone Reduces Neovascularization, Capillary Density and IGF-1 Receptor Phosphorylation in a Model of Oxygen-Induced Retinopathy.
M. E. Hartnett, D. J. Martiniuk, Y. Saito, P. Geisen, L. J. Peterson, and J. R. McColm (2006)
Invest. Ophthalmol. Vis. Sci. 47, 4975-4982
   Abstract »    Full Text »    PDF »
Postnatal head growth deficit among premature infants parallels retinopathy of prematurity and insulin-like growth factor-1 deficit..
C. Lofqvist, E. Engstrom, J. Sigurdsson, A.-L. Hard, A. Niklasson, U. Ewald, G. Holmstrom, L. E. H. Smith, and A. Hellstrom (2006)
Pediatrics 117, 1930-1938
   Abstract »    Full Text »    PDF »
T2-TrpRS Inhibits Preretinal Neovascularization and Enhances Physiological Vascular Regrowth in OIR as Assessed by a New Method of Quantification.
E. Banin, M. I. Dorrell, E. Aguilar, M. R. Ritter, C. M. Aderman, A. C. H. Smith, J. Friedlander, and M. Friedlander (2006)
Invest. Ophthalmol. Vis. Sci. 47, 2125-2134
   Abstract »    Full Text »    PDF »
Expression of Protein Kinase CK2 in Astroglial Cells of Normal and Neovascularized Retina.
A. A. Kramerov, M. Saghizadeh, H. Pan, A. Kabosova, M. Montenarh, K. Ahmed, J. S. Penn, C. K. Chan, D. R. Hinton, M. B. Grant, et al. (2006)
Am. J. Pathol. 168, 1722-1736
   Abstract »    Full Text »    PDF »
A GH receptor antisense oligonucleotide inhibits hepatic GH receptor expression, IGF-I production and body weight gain in normal mice..
G Tachas, S Lofthouse, C J Wraight, B F Baker, N B Sioufi, R A Jarres, A Berdeja, A M Rao, L M Kerr, E M d'Aniello, et al. (2006)
J. Endocrinol. 189, 147-154
   Abstract »    Full Text »    PDF »
Ontogeny of VEGF, IGF-I, and GH in Neonatal Rat Serum, Vitreous Fluid, and Retina from Birth to Weaning.
H. D. Modanlou, Z. Gharraee, J. Hasan, J. Waltzman, S. Nageotte, and K. D. A. Beharry (2006)
Invest. Ophthalmol. Vis. Sci. 47, 738-744
   Abstract »    Full Text »    PDF »
Molecular Endocrinology and Physiology of the Aging Central Nervous System.
R. G. Smith, L. Betancourt, and Y. Sun (2005)
Endocr. Rev. 26, 203-250
   Abstract »    Full Text »    PDF »
Evidence for Down-Regulation of Phosphoinositide 3-Kinase/Akt/Mammalian Target of Rapamycin (PI3K/Akt/mTOR)-Dependent Translation Regulatory Signaling Pathways in Ames Dwarf Mice.
Z. D. Sharp and A. Bartke (2005)
J. Gerontol. A Biol. Sci. Med. Sci. 60, 293-300
   Abstract »    Full Text »    PDF »
Residual {beta}-Cell Function More than Glycemic Control Determines Abnormalities of the Insulin-Like Growth Factor System in Type 1 Diabetes.
C. A. Hedman, J. Frystyk, T. Lindstrom, J.-W. Chen, A. Flyvbjerg, H. Orskov, and H. J Arnqvist (2004)
J. Clin. Endocrinol. Metab. 89, 6305-6309
   Abstract »    Full Text »    PDF »
A Conformationally Sensitive GHR [Growth Hormone (GH) Receptor] Antibody: Impact on GH Signaling and GHR Proteolysis.
J. Jiang, X. Wang, K. He, X. Li, C. Chen, P. P. Sayeski, M. J. Waters, and S. J. Frank (2004)
Mol. Endocrinol. 18, 2981-2996
   Abstract »    Full Text »    PDF »
Inhibition of Choroidal Neovascularization by a Peptide Inhibitor of the Urokinase Plasminogen Activator and Receptor System in a Mouse Model.
A. Das, N. Boyd, T. R. Jones, N. Talarico, and P. G. McGuire (2004)
Arch Ophthalmol 122, 1844-1849
   Abstract »    Full Text »    PDF »
Patterns of Gene Expression Reveal a Temporally Orchestrated Wound Healing Response in the Injured Spinal Cord.
M. J. Velardo, C. Burger, P. R. Williams, H. V. Baker, M. C. Lopez, T. H. Mareci, T. E. White, N. Muzyczka, and P. J. Reier (2004)
J. Neurosci. 24, 8562-8576
   Abstract »    Full Text »    PDF »
Insulin-Like Growth Factor-I Plays a Pathogenetic Role in Diabetic Retinopathy.
V. Poulaki, A. M. Joussen, N. Mitsiades, C. S. Mitsiades, E. F. Iliaki, and A. P. Adamis (2004)
Am. J. Pathol. 165, 457-469
   Abstract »    Full Text »    PDF »
Diabetic Retinopathy.
E. Stefansson and R. N. Frank (2004)
N. Engl. J. Med. 350, 2525-2526
   Full Text »    PDF »
Growth Hormone Receptor Antagonists.
A. F. Muller, J. J. Kopchick, A. Flyvbjerg, and A. J. van der Lely (2004)
J. Clin. Endocrinol. Metab. 89, 1503-1511
   Full Text »    PDF »
Diabetic Retinopathy.
R. N. Frank (2004)
N. Engl. J. Med. 350, 48-58
   Full Text »    PDF »
Angiogenesis and Antiangiogenesis in the Neonate: Relevance to Retinopathy of Prematurity.
A. Madan (2003)
NeoReviews 4, e356-363
   Full Text »    PDF »
Postnatal Serum Insulin-Like Growth Factor I Deficiency Is Associated With Retinopathy of Prematurity and Other Complications of Premature Birth.
A. Hellstrom, E. Engstrom, A.-L. Hard, K. Albertsson-Wikland, B. Carlsson, A. Niklasson, C. Lofqvist, E. Svensson, S. Holm, U. Ewald, et al. (2003)
Pediatrics 112, 1016-1020
   Abstract »    Full Text »    PDF »
Angiogenesis in Endocrine Tumors.
H. E. Turner, A. L. Harris, S. Melmed, and J. A. H. Wass (2003)
Endocr. Rev. 24, 600-632
   Abstract »    Full Text »    PDF »
The Kinase Inhibitor PKC412 Suppresses Epiretinal Membrane Formation and Retinal Detachment in Mice with Proliferative Retinopathies.
Y. Saishin, Y. Saishin, K. Takahashi, M.-S. Seo, M. Melia, and P. A. Campochiaro (2003)
Invest. Ophthalmol. Vis. Sci. 44, 3656-3662
   Abstract »    Full Text »    PDF »
CD105 prevents apoptosis in hypoxic endothelial cells.
C. Li, R. Issa, P. Kumar, I. N. Hampson, J. M. Lopez-Novoa, C. Bernabeu, and S. Kumar (2003)
J. Cell Sci. 116, 2677-2685
   Abstract »    Full Text »    PDF »
The Urokinase/Urokinase Receptor System in Retinal Neovascularization: Inhibition by A6 Suggests a New Therapeutic Target.
P. G. McGuire, T. R. Jones, N. Talarico, E. Warren, and A. Das (2003)
Invest. Ophthalmol. Vis. Sci. 44, 2736-2742
   Abstract »    Full Text »    PDF »
Insulin-like Growth Factor-I and its Receptor in Neovascular Age-Related Macular Degeneration.
A. C. Lambooij, K. H. M. van Wely, D. J. Lindenbergh-Kortleve, R. W. A. M. Kuijpers, M. Kliffen, and C. M. Mooy (2003)
Invest. Ophthalmol. Vis. Sci. 44, 2192-2198
   Abstract »    Full Text »    PDF »
Recruitment of a Repressosome Complex at the Growth Hormone Receptor Promoter and Its Potential Role in Diabetic Nephropathy.
P. M. Gowri, J. H. Yu, A. Shaufl, M. A. Sperling, and R. K. Menon (2003)
Mol. Cell. Biol. 23, 815-825
   Abstract »    Full Text »
Expression of IGFBP-3 by Human Retinal Endothelial Cell Cultures: IGFBP-3 Involvement in Growth Inhibition and Apoptosis.
P. E. Spoerri, S. Caballero, S. H. Wilson, L. C. Shaw, and M. B. Grant (2003)
Invest. Ophthalmol. Vis. Sci. 44, 365-369
   Abstract »    Full Text »    PDF »
Impact of Experimental Blockade of Peripheral Growth Hormone (GH) Receptors on the Kinetics of Endogenous and Exogenous GH Removal in Healthy Women and Men.
J. D. Veldhuis, M. Bidlingmaier, S. M. Anderson, W. S. Evans, Z. Wu, and C. J. Strasburger (2002)
J. Clin. Endocrinol. Metab. 87, 5737-5745
   Abstract »    Full Text »    PDF »
Deficit of Somatostatin-Like Immunoreactivity in the Vitreous Fluid of Diabetic Patients: Possible role in the development of proliferative diabetic retinopathy.
R. Simo, A. Lecube, L. Sararols, J. Garcia-Arumi, R. M. Segura, R. Casamitjana, and C. Hernandez (2002)
Diabetes Care 25, 2282-2286
   Abstract »    Full Text »    PDF »
Growth Hormone Receptor Antagonists: Discovery, Development, and Use in Patients with Acromegaly.
J. J. Kopchick, C. Parkinson, E. C. Stevens, and P. J. Trainer (2002)
Endocr. Rev. 23, 623-646
   Abstract »    Full Text »    PDF »
Cardiovascular Disease and Insulin-Like Growth Factor I.
J. Frystyk, T. Ledet, N. Moller, A. Flyvbjerg, and H. Orskov (2002)
Circulation 106, 893-895
   Full Text »    PDF »
IGF-I Is Critical for Normal Vascularization of the Human Retina.
A. Hellstrom, B. Carlsson, A. Niklasson, K. Segnestam, M. Boguszewski, L. de Lacerda, M. Savage, E. Svensson, L. Smith, D. Weinberger, et al. (2002)
J. Clin. Endocrinol. Metab. 87, 3413-3416
   Abstract »    Full Text »    PDF »
Retina-Specific Expression of PDGF-B Versus PDGF-A: Vascular Versus Nonvascular Proliferative Retinopathy.
K. Mori, P. Gehlbach, A. Ando, G. Dyer, E. Lipinsky, A. G. Chaudhry, S. F. Hackett, and P. A. Campochiaro (2002)
Invest. Ophthalmol. Vis. Sci. 43, 2001-2006
   Abstract »    Full Text »    PDF »
Pigment Epithelium-Derived Factor Suppresses Ischemia-Induced Retinal Neovascularization and VEGF-Induced Migration and Growth.
E. J. Duh, H. S. Yang, I. Suzuma, M. Miyagi, E. Youngman, K. Mori, M. Katai, L. Yan, K. Suzuma, K. West, et al. (2002)
Invest. Ophthalmol. Vis. Sci. 43, 821-829
   Abstract »    Full Text »    PDF »
Adenosine Receptor Antagonists and Retinal Neovascularization in Vivo.
R. P. Mino, P. E. Spoerri, S. Caballero, D. Player, L. Belardinelli, I. Biaggioni, and M. B. Grant (2001)
Invest. Ophthalmol. Vis. Sci. 42, 3320-3324
   Abstract »    Full Text »    PDF »
Enhanced Exercise-Induced GH Secretion in Subjects with Pro7 Substitution in the Prepro-NPY.
J. Kallio, U. Pesonen, M. K. Karvonen, M. Kojima, H. Hosoda, K. Kangawa, and M. Koulu (2001)
J. Clin. Endocrinol. Metab. 86, 5348-5352
   Abstract »    Full Text »    PDF »
An anti-angiogenic state in mice and humans with retinal photoreceptor cell degeneration.
J. Lahdenranta, R. Pasqualini, R. O. Schlingemann, M. Hagedorn, W. B. Stallcup, C. D. Bucana, R. L. Sidman, and W. Arap (2001)
PNAS 98, 10368-10373
   Abstract »    Full Text »    PDF »
Gene transfer by viral vectors into blood vessels in a rat model of retinopathy of prematurity.
I. Chowers, E. Banin, Y. Hemo, R. Porat, H. Falk, E. Keshet, J. Pe'er, and A. Panet (2001)
Br J Ophthalmol 85, 991-995
   Abstract »    Full Text »    PDF »
Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity.
A. Hellstrom, C. Perruzzi, M. Ju, E. Engström, A.-L. Hård, J.-L. Liu, K. Albertsson-Wikland, B. Carlsson, A. Niklasson, L. Sjödell, et al. (2001)
PNAS
   Abstract »    Full Text »
Preretinal Neovascularization Associated with Acetazolamide-Induced Systemic Acidosis in the Neonatal Rat.
S. Zhang, D. A. Leske, W. L. Lanier, B. A. Berkowitz, and J. M. Holmes (2001)
Invest. Ophthalmol. Vis. Sci. 42, 1066-1071
   Abstract »    Full Text »
Prenatal and Adult Growth Hormone Gene Expression in Rat Lymphoid Organs.
S. Recher, M. Raccurt, A. Lambert, P. E. Lobie, H. C. Mertani, and G. Morel (2001)
J. Histochem. Cytochem. 49, 347-354
   Abstract »    Full Text »
Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor.
V. Stellmach, S. E. Crawford, W. Zhou, and N. Bouck (2001)
PNAS
   Abstract »    Full Text »
VEGF Is Major Stimulator in Model of Choroidal Neovascularization.
N. Kwak, N. Okamoto, J. M. Wood, and P. A. Campochiaro (2000)
Invest. Ophthalmol. Vis. Sci. 41, 3158-3164
   Abstract »    Full Text »
Somatostatin Receptor 2A Expression in Choroidal Neovascularization Secondary to Age-Related Macular Degeneration.
A. C. Lambooij, R. W. A. M. Kuijpers, E. G. R. van Lichtenauer–Kaligis, M. Kliffen, G. S. Baarsma, P. M. van Hagen, and C. M. Mooy (2000)
Invest. Ophthalmol. Vis. Sci. 41, 2329-2335
   Abstract »    Full Text »
Mechanisms of Hepatocyte Growth Factor-Induced Retinal Endothelial Cell Migration and Growth.
W. Cai, S. L. Rook, Z. Y. Jiang, N. Takahara, and L. P. Aiello (2000)
Invest. Ophthalmol. Vis. Sci. 41, 1885-1893
   Abstract »    Full Text »
Growth Hormone Replacement Therapy Is Not Associated with Retinal Changes.
D. Blank, M. Riedl, A. Reitner, C. Schnack, G. Schernthaner, M. Clodi, H. Frisch, and A. Luger (2000)
J. Clin. Endocrinol. Metab. 85, 634-636
   Abstract »    Full Text »
Insulin-like Growth Factors in Pediatric Health and Disease.
D. LeRoith (1999)
J. Clin. Endocrinol. Metab. 84, 4355-4361
   Full Text »
Treatment of Diabetic Retinopathy.
F. L. Ferris, M. D. Davis, and L. M. Aiello (1999)
N. Engl. J. Med. 341, 667-678
   Full Text »    PDF »
Dramatic Inhibition of Retinal and Choroidal Neovascularization by Oral Administration of a Kinase Inhibitor.
M. S. Seo, N. Kwak, H. Ozaki, H. Yamada, N. Okamoto, E. Yamada, D. Fabbro, F. Hofmann, J. M. Wood, and P. A. Campochiaro (1999)
Am. J. Pathol. 154, 1743-1753
   Abstract »    Full Text »    PDF »
Severe proliferative diabetic retinopathy associated with acromegaly.
N. INOKUCHI, T. IKEDA, F. YASUDA, S. SHIRAI, and Y. UCHIHORI (1999)
Br J Ophthalmol 83, 628c-628
   Full Text »
Retinal Neovascularization Is Suppressed With a Matrix Metalloproteinase Inhibitor.
A. Das, A. McLamore, W. Song, and P. G. McGuire (1999)
Arch Ophthalmol 117, 498-503
   Abstract »    Full Text »    PDF »
Reduced Retinal Vascularization in Children with Growth Hormone Deficiency.
A. Hellström, E. Svensson, B. Carlsson, A. Niklasson, and K. Albertsson-Wikland (1999)
J. Clin. Endocrinol. Metab. 84, 795-798
   Abstract »    Full Text »
Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2.
L. Yang, S. C. Berk, S. P. Rohrer, R. T. Mosley, L. Guo, D. J. Underwood, B. H. Arison, E. T. Birzin, E. C. Hayes, S. W. Mitra, et al. (1998)
PNAS 95, 10836-10841
   Abstract »    Full Text »    PDF »
Basic Fibroblast Growth Factor Is Neither Necessary nor Sufficient for the Development of Retinal Neovascularization.
H. Ozaki, N. Okamoto, S. Ortega, M. Chang, K. Ozaki, S. Sadda, M. A. Vinores, N. Derevjanik, D. J. Zack, C. Basilico, et al. (1998)
Am. J. Pathol. 153, 757-765
   Abstract »    Full Text »    PDF »
Retinal Changes Mimicking Diabetic Retinopathy in Two Nondiabetic, Growth Hormone-Treated Patients.
E. A. Koller, L. Green, J. M. Gertner, M. Bost, and S. N. Malozowski (1998)
J. Clin. Endocrinol. Metab. 83, 2380-2383
   Abstract »    Full Text »
Evidence that upregulation of serum IGF-1 concentration can trigger acceleration of diabetic retinopathy.
E Chantelau (1998)
Br J Ophthalmol 82, 725-730
   Abstract »    Full Text »
Plasma endothelin-1 concentrations in patients with retinal vein occlusions.
A. Iannaccone, C. Letizia, S. Pazzaglia, E. M Vingolo, G. Clemente, and M. R Pannarale (1998)
Br J Ophthalmol 82, 498-503
   Abstract »    Full Text »
Treatment of Cystoid Macular Edema with Octreotide.
R. W.A.M. Kuijpers, S. Baarsma, and P. M. van Hagen (1998)
N. Engl. J. Med. 338, 624-626
   Full Text »
Why some cases of retinopathy worsen when diabetic control improves.
E Chantelau and E M Kohner (1997)
BMJ 315, 1105-1106
   Full Text »
Prevention of ischemia-induced retinopathy by the natural ocular antiangiogenic agent pigment epithelium-derived factor.
V. Stellmach, S. E. Crawford, W. Zhou, and N. Bouck (2001)
PNAS 98, 2593-2597
   Abstract »    Full Text »    PDF »
Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity.
A. Hellstrom, C. Perruzzi, M. Ju, E. Engstrom, A.-L. Hard, J.-L. Liu, K. Albertsson-Wikland, B. Carlsson, A. Niklasson, L. Sjodell, et al. (2001)
PNAS 98, 5804-5808
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)