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Patricia A D'Amore, Cindy Park-Windhol, Magali Saint-Geniez; Endomucin depletion inhibits pathologic retinal vascularization in vivo. Invest. Ophthalmol. Vis. Sci. 2017;58(8):4058. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Many ocular diseases such as retinopathy of prematurity (ROP) and wet age-related macular degeneration (AMD) involve abnormal retinal blood vessel growth. We previously demonstrated that endomucin-1 (EMCN), an endothelial cell-specific, sialic-rich glycoprotein, regulates normal retinal vessel development in vivo. Given that EMCN knockdown led to impaired developmental retinal vascularization, we examined the role of EMCN in the formation of pathological vessels.
The role of EMCN in pathologic vessel growth was assessed using the oxygen-induced retinopathy (OIR) and the laser-induced choroidal neovascularization (CNV) murine-models. For the OIR model, C57BL/6J pups were exposed to 75% oxygen between postnatal day (P) seven (P7) to P12 then injected intravitreally with siEMCN or scrambled siRNA (siCtrl) upon return to room air at P12. The areas of vaso-obliteration and neovascularization were measured at P17, time of maximal angiogenic response. Laser-induced CNV was created in C57BL/6J mice using a 532 nm laser under direct visualization using the Micron® fundus camera (4 spots/eye; 50 uM size, 50 ms, 550 Mw). Following the laser treatment mice received a single intravitreal injection of siEMCN or siCtrl. Lesions were confirmed by optical coherence tomography. The areas of CNV and extent of vessel leakage were determined by fluorescein angiography on days 7 and 14 post-laser.
Administration of siEMCN to mice following exposure to hyperoxia led to a reduction in avascular area (14.2±2.6% vs 22.6±4.7%, P<0.05) and neovascularization (2.6± 0.3% vs 3.5% ± 0.5%, P<0.05) in siEMCN retinas at P17 compared to siCtrl mice. At day 14, comparisons of fluorescein angiograms revealed that laser-induced CNV lesions in mice injected with siEMCN developed smaller and had significantly less leakage than in control mice (32.2±1.4% vs. 40.6±4.1%, P<0.05).
Reduction of EMCN expression using siRNA was associated with a reduction in pathological neovascularization in OIR and CNV. Our data indicate EMCN reduction/neutralization may be a potential therapy for treating pathologic ocular neovascularization.
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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