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Peter Heiduschka, Tanja Plagemann, Anne F. Alex, Nicole Eter; Effects of inhibition of neovascular signalling in a model of retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3459.
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© ARVO (1962-2015); The Authors (2016-present)
Retinopathy of prematurity (ROP) can be treated by blocking of VEGF. In a mouse model of ROP, we tested if blocking of placental growth factor (PlGF) would result in effects comparable to those achieved by anti-VEGF treatment. We also tested combined blocking of VEGF and PlGF and effects of Sunitinib that blocks many pro-angiogenic pathways.
C57BL/6 mice were exposed to 75% oxygen from postnatal days P7 to P12. After return to ambient air, intravitreal injections were performed. In three control groups, PBS or two neutral IgG molecules were injected. Mice of a fourth control group remained untouched after O2 treatment. In the treatment groups, antibodies against VEGF or PlGF, a mixture of anti-VEGF and anti-PlGF, and Sunitinib were injected. At least 10 eyes were evaluated in each group. On P17, electroretinographic (ERG) measurements were performed. The eyes were isolated, and blood vessels in retinal whole mounts were stained to evaluate avascular zones and neovascularisation. Results are expressed as percent of total retinal area with standard deviation (SD). Statistical analysis was done using the Kruskal-Wallis test.
Eyes of control groups showed similar neovascularisation (1.7-3.4%, SD 0.8-1.3%). Neovascularisation was clearly less (0.6-0.9%, SD 0.4-0.6%) in all treatment groups compared to controls (p<0.01 for antibodies and p<0.05 for sunitinib). Avascular zones in the retinas of all control groups showed similar values (15.6-22.7%, SD 4.6-8.8%). In eyes injected with anti-VEGF, avascular zones were reduced down to 4.0±2.7% (p<0.001 for control groups), but they were not reduced significantly when anti-PlGF, anti-VEGF+anti-PlGF or Sunitinib were injected (13.6-21.2%, SD 4.4-6.2%).ERG measurements did not reveal significant differences between the controls and the treatment groups. Amplitudes of a-waves were slightly larger in treated mice than in controls, and b-waves and amplitudes of oscillatory potentials were slightly larger in anti-VEGF treated mice than in all other groups.
Blocking of PlGF or injection of sunitinib results in a similar inhibition of neovascularisation as by anti-VEGF treatment in the mouse model of ROP. However, physiological angiogenesis that occurs after anti-VEGF treatment is blocked by anti-PlGF or sunitinib treatment. This indicates that pathological neovascularisation follows different pathways than physiological angiogenesis in ROP.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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