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F. vom Hagen, E. Langenkamp, P. J. Zwiers, H.-P. Hammes, G. Molema; Angiogenic and Inflammatory Genes Are Differentially Regulated and Expressed in Selected Retinal Areas in Experimental Proliferative Retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3129.
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© ARVO (1962-2015); The Authors (2016-present)
The common nature of proliferative retinopathies is the preretinal/intravitreal growth of new vessels, which originate from preexisting intraretinal vessels. Angiogenic and inflammatory factors play a role in pathologic angiogenesis. However, little is known about the spatial patterning and regulation of angiogenic and inflammatory genes in the initial phase of proliferative retinopathy.
We used the mouse model of retinopathy of prematurity. Eyes were obtained at postnatal day 13, i.e. after 5 days in hyperoxia, and one day in normoxia, when preretinal neovascularization (pNV) start. Vascularised retinal layers were dissected by laser dissection microscopy. The expression of 48 angiogenic and inflammatory genes was analysed in the dissected material and in retinal lysates of the contralateral eye using quantitative RT-PCR.
In control mice 9 of the 48 genes were predominantly expressed in the vascularized inner retinal layers, and 12 around the superficial vascular plexus, compared to the expression level of the whole retina. Thrombospondin-1 was preferentially expressed in the non-vascularized outer retina. In the ROP retina, 28 genes representing inflammation, angiogenesis, adhesion and remodelling were found in the vicinity of the superficial vascular plexus, from which neovascularizations arise. VEGF was expressed in the inner nuclear layer, while bFGF was abundant in the non-vascularizated outer retina. Compared with normoxic controls, 26 genes including TIMP-1, eNOS and iNOS were significantly upregulated.
The majority of the genes assessed were expressed close to or in the retinal vasculature at the onset of pNV. These genes located in areas from which pNV originate and are upregulated in ROP. Furthermore, ROP changes the spatial patterning of genes. These data promote the understanding of spatial regulation of angiogenic and inflammatory genes in the angiogenic mouse retina.
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