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hypoxic ischemic retinopathy

Nefeli Slavi, Abduqodir H Toychiev, Stylianos Kosmidis, Jessica Ackert, Stewart A Bloomfield, Heike Wulff, Suresh Viswanathan, Paul D Lampe, Miduturu Srinivas
Degeneration of retinal astrocytes precedes hypoxia-driven pathologic neovascularization and vascular leakage in ischemic retinopathies. However, the molecular events that underlie astrocyte loss remain unclear. Astrocytes abundantly express connexin 43 (Cx43), a transmembrane protein that forms gap junction (GJ) channels and hemichannels. Cx channels can transfer toxic signals from dying cells to healthy neighbors under pathologic conditions. Here we show that Cx43 plays a critical role in astrocyte apoptosis and the resulting preretinal neovascularization in a mouse model of oxygen-induced retinopathy...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Wenqin Xu, Jie Yin, Lijuan Sun, Zhicha Hu, Guorui Dou, Zifeng Zhang, Haiyan Wang, Changmei Guo, Yusheng Wang
The role of microglia in the pathophysiology of ischemic retinal diseases has been extensively studied. Retinal microglial activation may be correlated with retinal neovascularization in oxygen-induced retinopathy (OIR), an animal model that has been widely used in retinopathy of prematurity (ROP) research. Minocycline is an antibiotic that decreases microglial activation following hyperoxic and hypoxic-ischemic phases in neonatal rodents. Here, we investigated the effects of minocycline on vascularization and visual function...
August 8, 2017: Scientific Reports
Du Tran-Viet, Brittany M Wong, Shwetha Mangalesh, Ramiro Maldonado, C Michael Cotten, Cynthia A Toth
PURPOSE: The authors investigated feasibility of undilated handheld spectral domain optical coherence tomography (SDOCT) retinal imaging in preterm infants and children with neurologic abnormalities. METHODS: Under an institutional review board-approved protocol, the authors attempted handheld SDOCT imaging of the retina, choroid, and optic nerve in infants and young children without pupil dilation. Scans were analyzed for quality and successful capture of foveal, optic nerve, and retinal structural parameters and abnormalities...
May 29, 2017: Retina
Valeria E Lorenc, Paula V Subirada Caldarone, María C Paz, Darío G Ferrer, José D Luna, Gustavo A Chiabrando, María C Sánchez
In ischemic proliferative diseases such as retinopathies, persistent hypoxia leads to the release of numerous neovascular factors that participate in the formation of abnormal vessels and eventually cause blindness. The upregulation and activation of metalloproteinases (MMP-2 and MMP-9) represent a final common pathway in this process. Although many regulators of the neovascular process have been identified, the complete role of the insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) appears to be significantly more complex...
February 2018: Molecular Neurobiology
Xia Bai, Junpeng Luo, Xiaofeng Zhang, Jingjing Han, Zhaoyue Wang, Jingcheng Miao, Yanyan Bai
To evaluate the role of microRNA-126 (miR-126) in maintaining the integrity of the blood-retina barrier (BRB), we established a mouse model of oxygen-induced retinopathy (OIR) and measured the retinal levels of miR-126 using recombinant plasmid pCMV-MIR or pCMV-MIR-126 intravitreal injections. We also detected VCAM-1 and BCL2L11 levels. Retinal vaso-obliteration, VCAM-1 localization on retinal endothelial cells, the blood-retina vascular permeability or albumin leakage in retinas, TUNEL histology, Evans blue assays, or Western blotting for detecting albumin or tight junction levels in the retina was performed...
2017: Ophthalmic Research
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
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
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
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
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
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
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...
August 5, 2016: Scientific Reports
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
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
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
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
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
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
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
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
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