April 2014
Volume 55, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2014
Ciliary neurotrophic factor (CNTF) reduces neovascularization in the mouse-model of oxygen-induced retinopathy
Author Affiliations & Notes
  • Felicitas Bucher
    Eye Centre, Albert-Ludwigs-Universität Freiburg, Germany, Freiburg, Germany
  • Anima D Buehler
    Eye Centre, Albert-Ludwigs-Universität Freiburg, Germany, Freiburg, Germany
  • Gottfried Martin
    Eye Centre, Albert-Ludwigs-Universität Freiburg, Germany, Freiburg, Germany
  • Gunther R Schlunck
    Eye Centre, Albert-Ludwigs-Universität Freiburg, Germany, Freiburg, Germany
  • Hansjuergen Agostini
    Eye Centre, Albert-Ludwigs-Universität Freiburg, Germany, Freiburg, Germany
  • Andreas Stahl
    Eye Centre, Albert-Ludwigs-Universität Freiburg, Germany, Freiburg, Germany
  • Footnotes
    Commercial Relationships Felicitas Bucher, None; Anima Buehler, None; Gottfried Martin, None; Gunther Schlunck, None; Hansjuergen Agostini, None; Andreas Stahl, Novartis (F)
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 5408. doi:
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      Felicitas Bucher, Anima D Buehler, Gottfried Martin, Gunther R Schlunck, Hansjuergen Agostini, Andreas Stahl; Ciliary neurotrophic factor (CNTF) reduces neovascularization in the mouse-model of oxygen-induced retinopathy. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5408.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: Retinal ganglion cells (RGCs) have been shown to play important roles in retinal vascularization. For example, RGCs can express angiorepulsive factors like Sema3A. Neuroprotection could therefore be used as a new therapeutic approach to ameliorate vasoproliferative retinal diseases. This study examines the effect of ciliary neuroprotective factor (CNTF) on physiological and pathological vascularization in the mouse-model of oxygen-induced retinopathy (OIR-model). Ciliary neurotrophic factor (CNTF) is a well known neuroprotective agent that is currently investigated in multiple clinical trials for treatment of retinitis pigmentosa, ischemic neuropathy and macular teleangiectasia.

Methods: In the OIR model, newborn pups together with their nursing mother are exposed to hyperoxia (75% oxygen) from postnatal day 7 (P7) to P12. Following P12, pups are returned to room air. CNTF (500ng/µl) is administered intravitreally on P7 or P12 in one eye. The opposite eyes receive carrier-injections with PBS/BSA for intra-individual controls. The size of the vaso-obliterated area (VO) and the amount of neovascularization (NV) is determined on P17. To analyze the direct effect of CNTF on endothelial cell sprouting, CNTF is used in a spheroid-assay using human umbilical vein endothelial cells (HUVECS) in collagen with and without VEGF-stimulation.

Results: Intravitreal injections of CNTF on P12 (n=25 mice) but not on P7 (n=9 mice) results in a significant reduction of NV on P17 (P 12-injected: p= 0,021, P07-injected: p=0,59). In contrast, the size of the VO area at P17 remains unchanged in both groups, suggesting a selective anti-angiogenic effect of CNTF treatment on pathologic vessel formation. In the spheroid-assay, CNTF does not show any direct pro- or anti-angiogenic effect on endothelial cells. This can be explained by a lack of CNTF-receptor expression on both HUVECS as well as human retinal microvascular endothelial cells and suggests an indirect anti-angiogenic effect of CNTF in the OIR in vivo model.

Conclusions: CNTF potently reduces pathological NV in the OIR-model. According to our in vitro experiments, this effect cannot be attributed to a direct anti-angiogenic effect of CNTF on endothelial cells but is rather mediated by a third cell type.

Keywords: 706 retinopathy of prematurity • 700 retinal neovascularization • 531 ganglion cells  
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