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hypoxic ischemic retinopathy

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https://www.readbyqxmd.com/read/27861632/cgmp-phosphodiesterase-inhibition-prevents-hypoxia-induced-cell-death-activation-in-porcine-retinal-explants
#1
Lorena Olivares-González, Cristina Martínez-Fernández de la Cámara, David Hervás, María Pilar Marín, Agustin Lahoz, José María Millán, Regina Rodrigo
Retinal hypoxia and oxidative stress are involved in several retinal degenerations including diabetic retinopathy, glaucoma, central retinal artery occlusion, or retinopathy of prematurity. The second messenger cyclic guanosine monophosphate (cGMP) has been reported to be protective for neuronal cells under several pathological conditions including ischemia/hypoxia. The purpose of this study was to evaluate whether the accumulation of cGMP through the pharmacological inhibition of phosphodiesterase (PDE) with Zaprinast prevented retinal degeneration induced by mild hypoxia in cultures of porcine retina...
2016: PloS One
https://www.readbyqxmd.com/read/27797960/senescence-associated-secretory-phenotype-contributes-to-pathological-angiogenesis-in-retinopathy
#2
Malika Oubaha, Khalil Miloudi, Agnieszka Dejda, Vera Guber, Gaëlle Mawambo, Marie-Anne Germain, Guillaume Bourdel, Natalija Popovic, Flavio A Rezende, Randal J Kaufman, Frédérick A Mallette, Przemyslaw Sapieha
Pathological angiogenesis is the hallmark of diseases such as cancer and retinopathies. Although tissue hypoxia and inflammation are recognized as central drivers of vessel growth, relatively little is known about the process that bridges the two. In a mouse model of ischemic retinopathy, we found that hypoxic regions of the retina showed only modest rates of apoptosis despite severely compromised metabolic supply. Using transcriptomic analysis and inducible loss-of-function genetics, we demonstrated that ischemic retinal cells instead engage the endoplasmic reticulum stress inositol-requiring enzyme 1α (IRE1α) pathway that, through its endoribonuclease activity, induces a state of senescence in which cells adopt a senescence-associated secretory phenotype (SASP)...
October 26, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27734335/secretion-of-down-syndrome-critical-region-1-isoform-4-in-ischemic-retinal-ganglion-cells-displays-anti-angiogenic-properties-via-nfatc1-dependent-pathway
#3
Yue Xu, Boyu Yang, Yaguang Hu, Lin Lu, Xi Lu, Jiawei Wang, Qinmeng Shu, Qiaochu Cheng, Shanshan Yu, Fan Xu, Jingjing Huang, Xiaoling Liang
Down syndrome candidate region 1 (DSCR1) has two differentially regulated isoforms (DSCR1-1 and DSCR1-4) and is reported to play a role in a number of physiological processes, such as the inhibition of cardiac hypertrophy, attenuation of angiogenesis and carcinogenesis, and protection against neuronal death. However, the function of DSCR1 in the retina is still not clear. Therefore, we analyzed the expression and location of DSCR1 in the retina of neonatal mice with oxygen-induced retinopathy (OIR), and studied its effects on angiogenesis...
October 12, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27664289/anti-vascular-endothelial-growth-factor-agents-in-the-treatment-of-retinal-disease-from-bench-to-bedside
#4
Peter A Campochiaro, Lloyd Paul Aiello, Philip J Rosenfeld
The association of retinal hypoxia with retinal neovascularization has been recognized for decades, causing Michaelson to postulate in 1948 that a factor secreted by hypoxic retina was involved. The isolation of vascular endothelial growth factor (VEGF), characterization of its angiogenic activity, and demonstration that its expression was increased in hypoxic tissue made it a prime candidate. Intraocular levels of VEGF are elevated in patients with retinal or iris neovascularization, and VEGF-specific antagonists markedly suppress retinal neovascularization in mice and primates with ischemic retinopathy...
October 2016: Ophthalmology
https://www.readbyqxmd.com/read/27603537/role-of-insulinlike-growth-factor-1-in-fetal-development-and-in-the-early-postnatal-life-of-premature-infants
#5
Ann Hellström, David Ley, Ingrid Hansen-Pupp, Boubou Hallberg, Luca A Ramenghi, Chatarina Löfqvist, Lois E H Smith, Anna-Lena Hård
The neonatal period of very preterm infants is often characterized by a difficult adjustment to extrauterine life, with an inadequate nutrient supply and insufficient levels of growth factors, resulting in poor growth and a high morbidity rate. Long-term multisystem complications include cognitive, behavioral, and motor dysfunction as a result of brain damage as well as visual and hearing deficits and metabolic disorders that persist into adulthood. Insulinlike growth factor 1 (IGF-1) is a major regulator of fetal growth and development of most organs especially the central nervous system including the retina...
September 2016: American Journal of Perinatology
https://www.readbyqxmd.com/read/27572140/in-vivo-retinal-and-choroidal-hypoxia-imaging-using-a-novel-activatable-hypoxia-selective-near-infrared-fluorescent-probe
#6
Shinichi Fukuda, Kensuke Okuda, Genichiro Kishino, Sujin Hoshi, Itsuki Kawano, Masahiro Fukuda, Toshiharu Yamashita, Simone Beheregaray, Masumi Nagano, Osamu Ohneda, Hideko Nagasawa, Tetsuro Oshika
PURPOSE: Retinal hypoxia plays a crucial role in ocular neovascular diseases, such as diabetic retinopathy, retinopathy of prematurity, and retinal vascular occlusion. Fluorescein angiography is useful for identifying the hypoxia extent by detecting non-perfusion areas or neovascularization, but its ability to detect early stages of hypoxia is limited. Recently, in vivo fluorescent probes for detecting hypoxia have been developed; however, these have not been extensively applied in ophthalmology...
December 2016: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/27491345/in-vivo-imaging-of-retinal-hypoxia-in-a-model-of-oxygen-induced-retinopathy
#7
Md Imam Uddin, Stephanie M Evans, Jason R Craft, Megan E Capozzi, Gary W McCollum, Rong Yang, Lawrence J Marnett, Md Jashim Uddin, Ashwath Jayagopal, John S Penn
Ischemia-induced hypoxia elicits retinal neovascularization and is a major component of several blinding retinopathies such as retinopathy of prematurity (ROP), diabetic retinopathy (DR) and retinal vein occlusion (RVO). Currently, noninvasive imaging techniques capable of detecting and monitoring retinal hypoxia in living systems do not exist. Such techniques would greatly clarify the role of hypoxia in experimental and human retinal neovascular pathogenesis. In this study, we developed and characterized HYPOX-4, a fluorescence-imaging probe capable of detecting retinal-hypoxia in living animals...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27195131/neuroretinal-hypoxic-signaling-in-a-new-preclinical-murine-model-for-proliferative-diabetic-retinopathy
#8
Katherine J Wert, Vinit B Mahajan, Lijuan Zhang, Yuanqing Yan, Yao Li, Joaquin Tosi, Chun Wei Hsu, Takayuki Nagasaki, Kerstin M Janisch, Maria B Grant, MaryAnn Mahajan, Alexander G Bassuk, Stephen H Tsang
Diabetic retinopathy (DR) affects approximately one-third of diabetic patients and, if left untreated, progresses to proliferative DR (PDR) with associated vitreous hemorrhage, retinal detachment, iris neovascularization, glaucoma and irreversible blindness. In vitreous samples of human patients with PDR, we found elevated levels of hypoxia inducible factor 1 alpha (HIF1α). HIFs are transcription factors that promote hypoxia adaptation and have important functional roles in a wide range of ischemic and inflammatory diseases...
2016: Signal Transduction and Targeted Therapy
https://www.readbyqxmd.com/read/27116667/cell-therapy-applications-for-retinal-vascular-diseases-diabetic-retinopathy-and-retinal-vein-occlusion
#9
Susanna S Park
Retinal vascular conditions, such as diabetic retinopathy and retinal vein occlusion, remain leading causes of vision loss. No therapy exists to restore vision loss resulting from retinal ischemia and associated retinal degeneration. Tissue regeneration is possible with cell therapy. The goal would be to restore or replace the damaged retinal vasculature and the retinal neurons that are damaged and/or degenerating from the hypoxic insult. Currently, various adult cell therapies have been explored as potential treatment...
April 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/26621751/nrf2-in-ischemic-neurons-promotes-retinal-vascular-regeneration-through-regulation-of-semaphorin-6a
#10
Yanhong Wei, Junsong Gong, Zhenhua Xu, Rajesh K Thimmulappa, Katherine L Mitchell, Derek S Welsbie, Shyam Biswal, Elia J Duh
Delayed revascularization of ischemic neural tissue is a major impediment to preservation of function in central nervous system (CNS) diseases including stroke and ischemic retinopathies. Therapeutic strategies allowing rapid revascularization are greatly needed to reduce ischemia-induced cellular damage and suppress harmful pathologic neovascularization. However, key mechanisms governing vascular recovery in ischemic CNS, including regulatory molecules governing the transition from tissue injury to tissue repair, are largely unknown...
December 15, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26176867/activating-the-wnt-%C3%AE-catenin-pathway-did-not-protect-immature-retina-from-hypoxic-ischemic-injury
#11
Hsiu-Mei Huang, Chao-Ching Huang, Feng-Sheng Wang, Pi-Liang Hung, Ying-Chao Chang
PURPOSE: Visual loss associated with hypoxic-ischemic (HI) brain damage is the most common cause of visual impairment in children of developed countries. A neuroprotective role for Wnt/β-catenin signaling has been demonstrated in several neurodegenerative disorders. The association of Wnt signaling with HI injury in immature retina has not been established. METHODS: On postnatal day 7 (P7), HI was induced by unilateral common carotid artery ligation followed by 8% oxygen hypoxia for 2 hours...
July 2015: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/26039997/angiopoietin-like-4-is-a-potent-angiogenic-factor-and-a-novel-therapeutic-target-for-patients-with-proliferative-diabetic-retinopathy
#12
Savalan Babapoor-Farrokhran, Kathleen Jee, Brooks Puchner, Syed Junaid Hassan, Xiaoban Xin, Murilo Rodrigues, Fabiana Kashiwabuchi, Tao Ma, Ke Hu, Monika Deshpande, Yassine Daoud, Sharon Solomon, Adam Wenick, Gerard A Lutty, Gregg L Semenza, Silvia Montaner, Akrit Sodhi
Diabetic eye disease is the most common cause of severe vision loss in the working-age population in the developed world, and proliferative diabetic retinopathy (PDR) is its most vision-threatening sequela. In PDR, retinal ischemia leads to the up-regulation of angiogenic factors that promote neovascularization. Therapies targeting vascular endothelial growth factor (VEGF) delay the development of neovascularization in some, but not all, diabetic patients, implicating additional factor(s) in PDR pathogenesis...
June 9, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25796334/retinal-hypoxia-induces-vascular-endothelial-growth-factor-through-induction-of-estrogen-related-receptor-%C3%AE
#13
Ji Yeon Do, Young Keun Choi, Hyun Kook, Kyoungho Suk, In-Kyu Lee, Dong Ho Park
Ischemic retinopathies causing overexpression of pro-angiogenic factors, including vascular endothelial growth factor (VEGF), are the most common cause of blindness. Thus, understanding the pathophysiology of targetable pathways that regulate retinal VEGF is of great interest. A conserved binding site for estrogen-related receptor γ (ERRγ) has been identified in the promoter of the Vegfa gene. ERRγ is a constitutively active orphan nuclear receptor and its expression is increased by hypoxic stimuli in metabolically active tissues...
May 1, 2015: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/25795218/cell-specific-impact-of-nitric-oxide-dependent-guanylyl-cyclase-on-arteriogenesis-and-angiogenesis-in-mice
#14
Noomen Bettaga, Ronald Jäger, Sarah Dünnes, Dieter Groneberg, Andreas Friebe
Nitric oxide (NO) acts as essential regulator of vasculogenesis and angiogenesis and is critical for arteriogenesis. Whether NO's effects in vivo are mediated through NO-sensitive guanylyl cyclase (NO-GC) and thus by cGMP-dependent mechanisms has been only poorly addressed. Mice lacking NO-GC globally or specifically in smooth muscle cells (SMC) or endothelial cells (EC) were subjected to two established models for arteriogenesis and angiogenesis, namely hindlimb ischemia and oxygen-induced retinopathy. Our data clearly show the involvement of NO-GC in the recovery of blood flow after hindlimb ischemia, and this effect could be attributed to NO-GC in SMC...
July 2015: Angiogenesis
https://www.readbyqxmd.com/read/25673207/time-dependent-expression-of-pedf-and-vegf-in-blood-serum-and-retina-of-rats-with-oxygen-induced-retinopathy
#15
Chun-tao Lei, Xiao-ling Wu, Jie Peng, Xiao-feng Chen, Li-feng Qiao, Ying-chuan Fan, Jian-bin Hu
The effects of the balance changes of pigment epithelium growth factor (PEDF) and vascular endothelial growth factor (VEGF) in whole-body and retinal tissue on rats with oxygen-induced retinopathy were investigated. Forty-eight neonatal SD rats at the age of 7 days were randomly divided into 4 groups. The neonatal rats in experimental groups were exposed to 75% to 80% oxygen for 5 days and then to normal air, and those in control groups were kept feeding in normal air. At the age of 17 and 22 days, all the neonatal rats received retina angiography with FITC-dextran and the pathological changes of retinal vessels and perfusion were observed...
February 2015: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/25449932/neuro-ophthalmic-manifestations-of-prematurity
#16
Preeti Patil Chhablani, Ramesh Kekunnaya
Increasing rates of preterm births coupled with better survival of these infants have resulted in higher prevalence of systemic and ocular complications associated with prematurity. In addition to retinopathy of prematurity, infants who are born preterm may suffer from severe visual impairment as a result of hypoxic ischemic encephalopathy, hypoglycemia, and other metabolic imbalances. The effect of these processes on the anterior visual pathway may result in optic atrophy, optic nerve hypoplasia or optic disc cupping and affection of the posterior visual pathway leads to cortical visual impairment (CVI)...
October 2014: Indian Journal of Ophthalmology
https://www.readbyqxmd.com/read/25138030/thrombospondin-1-is-produced-by-retinal-glial-cells-and-inhibits-the-growth-of-vascular-endothelial-cells
#17
Yousef Yafai, Wolfram Eichler, Ianors Iandiev, Jan-Darius Unterlauft, Claudia Jochmann, Peter Wiedemann, Andreas Bringmann
BACKGROUND/AIMS: By the release of antiangiogenic factors, Müller glial cells provide an angiostatic environment in the normal and ischemic retina. We determined whether Müller cells produce thrombospondin-1 (TSP-1), a known inhibitor of angiogenesis. METHODS: Secretion of TSP-1 by cultured Müller cells was determined with ELISA. Slices of rat retinas and surgically excised retinal membranes of human subjects were immunostained against TSP-1 and the glial marker vimentin...
2014: Ophthalmic Research
https://www.readbyqxmd.com/read/24841813/-analysis-of-retinopathy-of-prematurity-with-birth-weight-higher-than-2-kg-in-xi-an-area
#18
Zifeng Zhang, Manhong Li, Yusheng Wang, Jing Wang, Xiaoyan Liu, Xiaojie Wang, Jing Fan
OBJECTIVE: To survey popularity and clinical characteristics of retinopathy of prematurity (ROP) in Xi'an area in infants with birth weight over 2 000 g. METHODS: Retrospective case-series study. ROP screening data of 1 866 infants was collected and reviewed from Department of Ophthalmology, Xijing Hospital from January 2008 to December 2012.One thousand eight hundreds and sixty-six cases (3 732 eyes) with 1 166 males and 700 females were examined. Their gestation age was (34 ± 4) weeks (24-46 weeks), and birth weight was (2 106 ± 743) g (730-4 900 g) ...
March 2014: [Zhonghua Yan Ke za Zhi] Chinese Journal of Ophthalmology
https://www.readbyqxmd.com/read/24825105/protective-and-antioxidant-effects-of-ppar%C3%AE-in-the-ischemic-retina
#19
Elizabeth Moran, Lexi Ding, Zhongxiao Wang, Rui Cheng, Qian Chen, Robert Moore, Yusuke Takahashi, Jian-xing Ma
PURPOSE: Previous studies have demonstrated that peroxisome proliferator-activated receptor-alpha (PPARα) agonists have therapeutic effects in diabetic retinopathy, although the mechanism of action remains incompletely understood. The purpose of this study was to evaluate PPARα's protective effects in the ischemic retina, and to delineate its molecular mechanism of action. METHODS: For the oxygen-induced retinopathy (OIR) model, wild-type (WT), and PPARα knockout (PPARα(-/-)) mice were exposed to 75% O₂ from postnatal day 7 (P7) to P12 and treated with the PPARα agonist fenofibric acid (Feno-FA) from P12 to P16...
May 13, 2014: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/24168070/dilated-iris-vasculature-in-the-setting-of-the-neonatal-hypoxic-encephelopathy
#20
Ian R Gorovoy, Jordan C Vaccari
The differential diagnosis of dilated iris vasculature in a neonate includes retinopathy of prematurity with anterior segment plus disease, persistent fetal vasculature, intrauterine cocaine exposure, maternal diabetes, and other pathologies associated with iris neovascularization and ischemia seen in adult populations, such as central retinal vein occlusions, ocular ischemic syndrome, and chronic retinal detachment. We present neonatal hypoxic ischemic encephalopathy as a new etiology of dilated iris vasculature in a male baby who suffered a large in-utero brain vasculature insult three weeks prior to delivery but with normal fundi, no risk factors for retinopathy of prematurity (normal birth weight, and gestational age), and no other explanatory etiologies...
July 2015: Seminars in Ophthalmology
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