| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Improves Physiological Angiogenesis and Reduces Pathological Neovascularization in Ischemic Retinopathy
From Ophthalmology and Vision Science,* Queen’s University Belfast, Belfast, Northern Ireland; and Cytokine PharmaSciences, Inc., King of Prussia, Pennsylvania
The present study was undertaken to test whether inhibition of the proangiogenic inflammatory cytokine tumor necrosis factor (TNF)-
can modulate retinal hypoxia and preretinal neovascularization in a murine model of oxygen-induced retinopathy (OIR). OIR was produced in TNF-–/– and wild-type (WT) control C57B6 neonatal mice by exposure to 75% oxygen between postnatal days 7 and 12 (P7 to P12). Half of each WT litter was treated with the cytokine inhibitor semapimod (formerly known as CNI-1493) (5 mg/kg) by daily intraperitoneal injection from the time of reintroduction to room air at P12 until P17. The extent of preretinal neovascularization and intraretinal revascularization was quantified by image analysis of retinal flat-mounts and retinal hypoxia correlated with vascularization by immunofluorescent localization of the hypoxia-sensitive drug pimonidazole (hypoxyprobe, HP). HP adducts were also characterized by Western analysis and quantified by competitive enzyme-linked immunosorbent assay. TNF-–/– and WT mice showed a similar sensitivity to hyperoxia-induced retinal ischemia at P12. At P13 some delay in early reperfusion was evident in TNF-–/– and WT mice treated with semapimod. However, at P17 both these groups had significantly better vascular recovery with less ischemic/hypoxic retina and preretinal neovascularization compared to untreated retinopathy in WT mice. Immunohistochemistry showed deposition of HP in the avascular inner retina but not in areas underlying preretinal neovascularization, indicating that such aberrant vasculature can reduce retinal hypoxia. Inhibition of TNF- significantly improves vascular recovery within ischemic tissue and reduces pathological neovascularization in OIR. HP provides a useful tool for mapping and quantifying tissue hypoxia in experimental ischemic retinopathy.
This article has been cited by other articles:
 |
|
 |
|
  H. Zhao, H. Jin, Q. Li, Q. Gu, Z. Zheng, H. Wu, S. Ye, X. Sun, X. Xu, and P. C. P. Ho Inhibition of Pathologic Retinal Neovascularization by a Small Peptide Derived from Human Apolipoprotein(a) Invest. Ophthalmol. Vis. Sci., November 1, 2009; 50(11): 5384 - 5395. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Zhang, M. Rojas, B. Lilly, N.-T. Tsai, T. Lemtalsi, G. I. Liou, R. W. Caldwell, and R. B. Caldwell NAD(P)H Oxidase-Dependent Regulation of CCL2 Production during Retinal Inflammation Invest. Ophthalmol. Vis. Sci., June 1, 2009; 50(6): 3033 - 3040. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Guma, J. Rius, K. X. Duong-Polk, G. G. Haddad, J. D. Lindsey, and M. Karin Genetic and pharmacological inhibition of JNK ameliorates hypoxia-induced retinopathy through interference with VEGF expression PNAS, May 26, 2009; 106(21): 8760 - 8765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Higuchi, K. Ohashi, S. Kihara, K. Walsh, and N. Ouchi Adiponectin Suppresses Pathological Microvessel Formation in Retina Through Modulation of Tumor Necrosis Factor-{alpha} Expression Circ. Res., May 8, 2009; 104(9): 1058 - 1065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Berger, S. I. Savitz, S. Nijhawan, M. Singh, J. David, P. S. Rosenbaum, and D. M. Rosenbaum Deleterious Role of TNF-{alpha} in Retinal Ischemia-Reperfusion Injury Invest. Ophthalmol. Vis. Sci., August 1, 2008; 49(8): 3605 - 3610. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Cai, O. Kehoe, G. M. Smith, P. Hykin, and M. E. Boulton The Angiopoietin/Tie-2 System Regulates Pericyte Survival and Recruitment in Diabetic Retinopathy Invest. Ophthalmol. Vis. Sci., May 1, 2008; 49(5): 2163 - 2171. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ruiz-Ederra and A. S. Verkman Aquaporin-1 Independent Microvessel Proliferation in a Neonatal Mouse Model of Oxygen-Induced Retinopathy Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4802 - 4810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. de Gooyer, K. A. Stevenson, P. Humphries, D. A. C. Simpson, T. M. Curtis, T. A. Gardiner, and A. W. Stitt Rod Photoreceptor Loss in Rho-/- Mice Reduces Retinal Hypoxia and Hypoxia-Regulated Gene Expression Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5553 - 5560. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. E. de Gooyer, K. A. Stevenson, P. Humphries, D. A. C. Simpson, T. A. Gardiner, and A. W. Stitt Retinopathy Is Reduced during Experimental Diabetes in a Mouse Model of Outer Retinal Degeneration Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5561 - 5568. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kociok, S. Radetzky, T. U. Krohne, C. Gavranic, and A. M. Joussen Pathological but Not Physiological Retinal Neovascularization Is Altered in TNF-Rp55-Receptor-Deficient Mice Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 5057 - 5065. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Falconer, J.M. Mwenda, D.C. Chai, C. Wagner, X.Y. Song, A. Mihalyi, P. Simsa, C. Kyama, F.J. Cornillie, A. Bergqvist, et al. Treatment with anti-TNF monoclonal antibody (c5N) reduces the extent of induced endometriosis in the baboon Hum. Reprod., July 1, 2006; 21(7): 1856 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Banin, M. I. Dorrell, E. Aguilar, M. R. Ritter, C. M. Aderman, A. C. H. Smith, J. Friedlander, and M. Friedlander T2-TrpRS Inhibits Preretinal Neovascularization and Enhances Physiological Vascular Regrowth in OIR as Assessed by a New Method of Quantification Invest. Ophthalmol. Vis. Sci., May 1, 2006; 47(5): 2125 - 2134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sriwijitkamol, C. Christ-Roberts, R. Berria, P. Eagan, T. Pratipanawatr, R. A. DeFronzo, L. J. Mandarino, and N. Musi Reduced Skeletal Muscle Inhibitor of {kappa}B{beta} Content Is Associated With Insulin Resistance in Subjects With Type 2 Diabetes: Reversal by Exercise Training Diabetes, March 1, 2006; 55(3): 760 - 767. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
