Liya Wang1, Pingling Shi1, Zhongzhong Xu1, Jing Li1, Yanting Xie1, Kenneth Mitton2, Kimberly Drenser2, Qi Yan3. 1. Henan Eye Institute and Henan Eye Hospital, Zhengzhou, Henan, China. 2. Eye Research Institute, Pediatric Retinal Research Lab, Oakland University, Rochester, Michigan, United States. 3. Henan Eye Institute and Henan Eye Hospital, Zhengzhou, Henan, China Eye Research Institute, Pediatric Retinal Research Lab, Oakland University, Rochester, Michigan, United States.
Abstract
PURPOSE: Retinopathy of prematurity (ROP) is directly associated with abnormal expression of retinal vascular endothelial growth factor (VEGF) in premature neonates. This study was to investigate whether the systemic administration of retinoic acid (RA) regulates retinal VEGF expression and prevents retinal neovascularization and retinopathy in the oxygen-induced retinopathy (OIR) mouse model. METHODS: C57BL/6 mice were subjected to OIR by exposure to 75% oxygen from postnatal day (P) 7 to 12 of age. RA was intraperitoneally injected daily to pups from P6 to P9. Retinal whole mount staining and image analysis, immunostaining, Western blotting, quantitative RT-PCR, TUNEL assay, and electroretinography were performed to evaluate the effects of RA on VEGF expression, retinal neovascularization, and retinal neuron functions. RESULTS: Systemic administration of RA in OIR mice promoted retinal VEGF mRNA and protein expression in phase I; the stabilized level of VEGF in phase I supported retinal vascular development and counteracted vaso-obliteration in OIR mice. Subsequently, the excessive generation of VEGF in phase II was attenuated; the retinal vascular leakage and apoptotic cells were significantly ameliorated. As a result, RA significantly prevented the development of hypoxia-induced retinal neovascularization and retinopathy in OIR mice and improved the functional recovery of retinal neurons downstream of photoreceptor cells as measured by focal electroretinography. CONCLUSIONS: Systemic administration of RA regulates retinal VEGF expression and supports retinal vascular development in OIR mouse model. We propose that systemic administration of RA to extremely low birth weight, preterm infants during oxygen therapy could potentially be an effective therapeutic approach for the prevention of ROP. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
PURPOSE:Retinopathy of prematurity (ROP) is directly associated with abnormal expression of retinal vascular endothelial growth factor (VEGF) in premature neonates. This study was to investigate whether the systemic administration of retinoic acid (RA) regulates retinal VEGF expression and prevents retinal neovascularization and retinopathy in the oxygen-induced retinopathy (OIR) mouse model. METHODS: C57BL/6 mice were subjected to OIR by exposure to 75% oxygen from postnatal day (P) 7 to 12 of age. RA was intraperitoneally injected daily to pups from P6 to P9. Retinal whole mount staining and image analysis, immunostaining, Western blotting, quantitative RT-PCR, TUNEL assay, and electroretinography were performed to evaluate the effects of RA on VEGF expression, retinal neovascularization, and retinal neuron functions. RESULTS: Systemic administration of RA in OIR mice promoted retinal VEGF mRNA and protein expression in phase I; the stabilized level of VEGF in phase I supported retinal vascular development and counteracted vaso-obliteration in OIR mice. Subsequently, the excessive generation of VEGF in phase II was attenuated; the retinal vascular leakage and apoptotic cells were significantly ameliorated. As a result, RA significantly prevented the development of hypoxia-induced retinal neovascularization and retinopathy in OIR mice and improved the functional recovery of retinal neurons downstream of photoreceptor cells as measured by focal electroretinography. CONCLUSIONS: Systemic administration of RA regulates retinal VEGF expression and supports retinal vascular development in OIR mouse model. We propose that systemic administration of RA to extremely low birth weight, preterm infants during oxygen therapy could potentially be an effective therapeutic approach for the prevention of ROP. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.
Authors: Wendy A Dailey; Kimberly A Drenser; Sui Chien Wong; Mei Cheng; Joseph Vercellone; Kevin K Roumayah; Erin V Feeney; Mrinalini Deshpande; Alvaro E Guzman; Michael Trese; Kenneth P Mitton Journal: Exp Eye Res Date: 2017-08-18 Impact factor: 3.467
Authors: Magali E Ridano; Paula V Subirada; María C Paz; Valeria E Lorenc; Juan C Stupirski; Ana L Gramajo; José D Luna; Diego O Croci; Gabriel A Rabinovich; María C Sánchez Journal: Oncotarget Date: 2017-05-16