Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
This PDF is available to Subscribers Only