Project description:Different inbred strains of rats differ in their susceptibility to OIR, an animal model of human retinopathy of prematurity. We examined gene expression profiles in Fischer 344 (F344, resistant to OIR) and Sprague Dawley (SD, susceptible to OIR) rats at the early time points of day 5 (in response to hyperoxia) and day 6 (in response to relative hypoxia) to identify gene pathways related to the underlying genetic cause of the phenotypic differences observed between strains. To examine gene expression changes in rat strains which are resistant and susceptible to OIR, four different experimental conditions were analysed: F344 cyclic hyperoxia (O2) exposed, F344 room air (RA) exposed, SD O2 exposed and SD RA exposed. Two samples of pooled RNA, comprising of 3 individual rats from 2 separate litters, was used for each experimental condition, for each time point of interest. Pooled RNA from age-matched room air-exposed rats were used as controls.
Project description:To study early and late transcriptional changes introduced to blood and retinal tissue in murine oxygen-induced retinopathy (OIR). From retinal cells RNA was extracted at three time points: immediately after end of hyperoxia (P12), at P17 and P28.
Project description:To study early and late transcriptional changes introduced to blood and retinal tissue in murine oxygen-induced retinopathy (OIR). From blood MNCs total RNA was extracted at three time points: immediately after end of hyperoxia (P12), at P17 and P28.
Project description:Different inbred strains of rats differ in their susceptibility to OIR, an animal model of human retinopathy of prematurity. We examined gene expression profiles in Fischer 344 (F344, resistant to OIR) and Sprague Dawley (SD, susceptible to OIR) rats at the early time points of day 5 (in response to hyperoxia) and day 6 (in response to relative hypoxia) to identify gene pathways related to the underlying genetic cause of the phenotypic differences observed between strains.
Project description:Activation of anaplerosis takes away glutamine from the biosynthetic pathway to the energy-producing TCA cycle. Especially, induction of hyperoxia driven anaplerosis in neurovascular tissues such as the retina during early stages of development could deplete biosynthetic precursors from newly proliferating endothelial cells impeding physiological angiogenesis and leading to vasoobliteration. Using an oxygen-induced retinopathy (OIR) mouse model, we investigated the metabolic differences between OIR-resistant BALB/cByJ and OIR susceptible C57BL/6J strains at system levels to understand the molecular underpinnings that potentially contribute to hyperoxia-induced vascular abnormalities in the neural retina. Our systems level in vivo RNA-seq, proteomic, and lipidomic profiling and ex-vivo explant studies show that the medium-chain fatty acids serves as an alternative source to feed the TCA cycle. Our findings strongly implicate that medium-chain fatty acids could suppress glutamine-fueled anaplerosis and ameliorate hyperoxia-induced vascular abnormalities in conditions such as retinopathy of prematurity.
Project description:Activation of anaplerosis takes away glutamine from the biosynthetic pathway to the energy-producing TCA cycle. Especially, induction of hyperoxia driven anaplerosis in neurovascular tissues such as the retina during early stages of development could deplete biosynthetic precursors from newly proliferating endothelial cells impeding physiological angiogenesis and leading to vasoobliteration. Using an oxygen-induced retinopathy (OIR) mouse model, we investigated the metabolic differences between OIR-resistant BALB/cByJ and OIR susceptible C57BL/6J strains at system levels to understand the molecular underpinnings that potentially contribute to hyperoxia-induced vascular abnormalities in the neural retina. Our systems level in vivo RNA-seq, proteomic, and lipidomic profiling and ex-vivo explant studies show that the medium-chain fatty acids serves as an alternative source to feed the TCA cycle. Our findings strongly implicate that medium-chain fatty acids could suppress glutamine-fueled anaplerosis and ameliorate hyperoxia-induced vascular abnormalities in conditions such as retinopathy of prematurity.
Project description:To identify the N6-methyladenosine (m6A) modified circular RNAs (circRNAs) involved in a mouse model of oxygen-induced retinopathy (OIR), microarray analysis was performed with the retinal samples from OIR mice and Room air controls.
Project description:We aimed at identifying the regulatory network of Aflibercept in the context of pathological neovascularization by using the oxygen-induced retinopathy mouse model as a surrogate of proliferative diabetic retinopathy Total RNA was collected from entire retinal cups dissected from 50-days old mice subjected to the oxygen-induced retinopathy protocol and subsequently injected with Aflibercept either on postnatal days 13 and 15 (OIR+AFLx2) or on postnatal days 13, 15 and 17. Non-injected OIR littermates (OIR) and age-matched mice housed in normoxic conditions (normoxia) were used as controls.
Project description:We aimed at identifying the regulatory network of Aflibercept in the context of pathological neovascularization by using the oxygen-induced retinopathy mouse model as a surrogate of proliferative diabetic retinopathy Total RNA was collected from entire retinal cups dissected from 19-days old mice subjected to the oxygen-induced retinopathy protocol and subsequently injected with Aflibercept either on postnatal days 13 and 15 (OIR+AFLx2) or on postnatal days 13, 15 and 17. Non-injected OIR littermates (OIR) and age-matched mice housed in normoxic conditions (normoxia) were used as controls.
