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Chintan Patel, PRAHALATHAN PICHAVARAM, Manuela Cervelli, Ruth B Caldwell, S. Priya Narayanan; Overexpression of spermine oxidase in retinal neurons aggravates vascular injury in a model of retinopathy of prematurity. Invest. Ophthalmol. Vis. Sci. 2017;58(8):3463.
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© ARVO (1962-2015); The Authors (2016-present)
Retinopathy of prematurity (ROP), continues to be a major cause of childhood blindness all over the world. Using an oxygen-induced retinopathy (OIR) mouse model of ROP, we have previously shown that inhibition of polyamine oxidases using MDL 72527 significantly reduced vascular injury and microglial activation (Patel et al., 2016). Spermine Oxidase (SMO, a polyamine oxidase) is a key enzyme in polyamine catabolism. In this study, we investigated the impact of specific overexpression of SMO in retinal neurons on mediating vascular injury.
Newborn Calbindin-cre-SMOf/f transgenic mice overexpressing SMO in horizontal and amacrine cells (SMO Tg) and littermate (WT) control mice were maintained in 70% oxygen from postnatal day (P) 7 to 12 followed by normoxia until P17. Animals were sacrificed at different stages of OIR treatment and eyes were processed for different studies. Retinal cryostat sections were prepared for immunostaining analysis. Analysis of vaso-obliteration and neovascularization were performed on retinal flatmounts.
In SMO Tg model, vascular development is normal and SMO is over expressed in horizontal and amacrine cells, which are ideally situated to interact with the vasculature. Untreated SMO Tg retinas showed normal vascular development. Vaso-obliteration analyses using Isolectin B4 on retinal flatmounts showed significantly increased avascular area at P12 and P17 in SMO Tg retina compared to control OIR treated retina (p<0.05, N=5). Quantitation of neovascular tufts (NV) on retinal flatmounts revealed significant increases in pathological NV area in SMO Tg OIR retina compared to control OIR retinas at P17 (p<0.05, N=3). Immunolabeling studies using GFAP antibody demonstrated that glial activation was also increased in SMO Tg OIR retina compared to control OIR retinas at P17. These data demonstrate a specific role for neuronal SMO in mediating OIR-induced retinal vascular injury. Molecular mechanisms by which SMO mediates glial activation and vascular damage in OIR retina are currently under investigation.
Our data suggest a significant role of neuronal SMO in mediating vascular damage and glial activation in the OIR retina. Calbindin-cre-SMOf/f transgenic mouse is an excellent tool to investigate the neuro-vascular interactions and regulatory mechanisms in retinal disease models.
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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