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Hidenori Ishihama, Masaharu Ohbayashi, Nobuyuki Kurosawa, Takashi Kitsukawa, Onrai Matsuura, Yozo Miyake, Takashi Muramatsu; Colocalization of Neuropilin-1 and Flk-1 in Retinal Neovascularization in a Mouse Model of Retinopathy. Invest. Ophthalmol. Vis. Sci. 2001;42(6):1172-1178.
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purpose. To investigate the mechanisms of the development of retinal
neovascularization, the localizations of vascular endothelial (VEGF)
receptors Flk-1 and neuropilin (NP)-1 mRNAs were examined.
methods. The model of retinopathy of prematurity (ROP) was produced by
ischemia-induced ocular neovascularization, by exposing postnatal day-7
mice to 75% oxygen for 5 days and then returning them to room air for
5 days. Retinal neovascularization was visualized by injection of
fluorescein-dextran. Expression of Flk-1 and NP-1 mRNAs were examined
by in situ hybridization with flatmount and serial sections of the
retina. The localization of NP-1 was also confirmed by
immunohistochemistry. Blood vessel patterns were characterized by
immunohistochemical localization of von Willebrand factor (vWF).
results. Flatmount in situ hybridization showed intense expression of NP-1 and
Flk-1 mRNAs colocalized in the area of neovascularization. In situ
hybridization of serial sections of the retina revealed that expression
of Flk-1 and NP-1 was restricted to neovascularized vessels of the
retina from ROP mice.
conclusions. The restricted expression of Flk-1 and NP-1 on neovascularized vessels
suggests that these molecules may play important roles in retinal
neovascularization. This is the first report of the colocalization of
NP-1 and Flk-1 on neovascularized vessels of the retina from ROP
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