Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 44-year-old man developed bilateral blindness following severe periorbital cellulitis and pansinusitis. CT and MR imaging demonstrated bilateral cavernous sinus thrombosis. Diffusion-weighted imaging revealed reduced apparent diffusion coefficient in bilateral optic nerves, suggesting optic nerve ischemia caused by the cavernous sinus thrombophlebitis (CST). Following surgical debridement of pansinusitis, antimicrobial therapy, and anticoagulation, the patient recovered from the infectious episode but sustained permanent bilateral blindness. This case shows that both retinal and optic nerve ischemia can be the cause of blindness after CST. Arguments supporting an arterial-versus-venous origin for the ischemia are discussed.
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PMID:Restricted diffusion in bilateral optic nerves and retinas as an indicator of venous ischemia caused by cavernous sinus thrombophlebitis. 1703 47

Ocular neovascularization (NV) is the primary cause of blindness in a wide range of ocular diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). The exact mechanism underlying the pathogenesis of ocular NV is not yet well understood, and as a consequence, there is no satisfactory therapy for ocular NV. In the last 10 years, a number of studies provided increasing evidence demonstrating that the imbalance between angiogenic stimulating factors and angiogenic inhibitors is a major contributor to the angiogenesis induced by various insults, such as hypoxia or ischemia, inflammation and tumor. The angiogenic inhibitors alone or in combination with other existing therapies are, therefore, believed to be promising in the treatment of ocular NV in the near future. This article reviews recent progress in studies on the mechanisms and treatment of ocular NV, focusing on the implication and therapeutic potential of endogenous angiogenic inhibitors in ocular NV.
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PMID:Ocular neovascularization: Implication of endogenous angiogenic inhibitors and potential therapy. 1707 26

Age-related maculopathy (ARM) has become the major cause of blindness in the Western World. Currently its pathogenesis and primary site of functional damage is not fully understood but ischemia is believed to play a major role. Early detection and precise monitoring of progression of ARM are main goals of current research due to lack of sufficient treatment options, especially in the dry, atrophic form of this disease. We applied the multifocal electroretinogram (mfERG) that can detect any local functional deficit objectively in the central retina. We recorded two paradigms in early ARM patients, the fast flicker and the slow flash paradigm which both represent fast adaptation processes of the proximal retina but under differing photopic conditions and stimulation rates. By subtracting the waveform responses we extracted a late component in the difference waveform that was significantly reduced in the early ARM group compared to a healthy control group (p < or = 0.05). We propose that this multifocal nonlinear analysis permits the detection of adaptative deficits and provides topographic mapping of retinal dysfunction in early ARM. The difference waveform component we extracted with this novel approach might indicate early functional loss in ARM caused by ischemia in postreceptoral layers such as bipolar cells and inner plexiform regions.
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PMID:Postreceptoral adaptation abnormalities in early age-related maculopathy. 1726 78

Retinal ischemia is a common cause of visual impairment and blindness. However, despite the significant advances that have been made in understanding the pathophysiology of retinal ischemia, effective treatments are still lacking. The goal of these studies was to use an in vitro model to identify molecules that could be neuroprotective for retinal ganglion cells exposed to ischemia. Ischemia was induced in the rat retinal ganglion cell line, RGC-5, using iodoacetic acid (IAA). Brief treatment with IAA resulted in RGC-5 cell death within 24 h by a non-apoptotic mechanism. Similar to ischemia in vivo, IAA treatment caused a rapid loss of ATP to approximately 50% of control levels. In contrast, changes in markers of oxidative stress occurred more slowly and included an increase in reactive oxygen species and a decrease in glutathione. Specific flavonoids were able to prevent the cell death caused by IAA treatment. Some of the flavonoids also prevented the loss of ATP as well as the changes in markers of oxidative stress. In contrast, classical antioxidants had only a very modest effect on IAA-induced cell death. These results suggest that specific flavonoids may be useful in preventing ischemia-induced retinal ganglion cell death in vivo.
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PMID:Flavonoids protect retinal ganglion cells from ischemia in vitro. 1816 67

Diabetic retinopathy is one of the most common diabetic complications, and is a major cause of new blindness in the working-age population of developed countries. Progression of vascular abnormalities, including the selective loss of pericytes, formation of acellular capillaries, thickening of the basement membrane, and increased vascular permeability characterizes early nonproliferative diabetic retinopathy (NPDR). Capillary occlusion, as shown on fluorescein angiograms, is also one of the earliest clinically recognizable lesion of NPDR. In response to capillary non-perfusion, there is dilation of neighbouring capillaries, leading to early blood-retinal barrier breakdown, capillary non-perfusion, and endothelial cell injury and death. The resulting ischemia leads to increased production of growth factors, and the development of proliferative diabetic retinopathy (PDR), which is characterized by growth of new vessels and potential severe and irreversible visual loss. The exact pathogenic mechanism by which capillary non-perfusion occurs is still unclear but growing evidence now suggests that increased leukocyte-endothelial cell adhesion and entrapment (retinal leukostasis) in retinal capillaries is an early event associated with areas of vascular non-perfusion and the development of diabetic retinopathy. The leukocytes in diabetic patients are less deformable more activated, and demonstrate increased adhesion to the vascular endothelium. This review summarizes the current literature on the role of leukocytes in the pathogenesis of capillary occlusion, and discusses the potential of leukostasis as a new promising target in the treatment of diabetic retinopathy.
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PMID:Leukocytes in diabetic retinopathy. 1822 Jun 51

Retinal neovascularization (RNV) is one of the most important causes of blindness. No efficient treatment for RNV is available. Pigment epithelium-derived factor (PEDF) is a natural inhibitor of angiogenesis. It plays an important role in the modulation of ocular neovascularization. It has been demonstrated recently that the ischemia-induced retinal neovascularization can be dramatically inhibited by the recombinant PEDF protein or local viral vector-mediated delivery of PEDF cDNA, which predicts PEDF to be an optional strategy for intractable retinal angiogenic diseases like diabetic retinopathy, retinopathy of prematurity, and central retinal vein occlusion. Therefore, it is necessary to review the biological aspects of PEDF, its effect on the inhibition of angiogenesis and the prospect of using PEDF for the treatment of retinal neovascularization.
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PMID:[Pigment epithelium-derived factor and its application in retinal angiogenic diseases]. 1830 52

Aberrant angiogenesis in the eye is the most common cause of blindness. The current study examined the role of interleukin-10 (IL-10) in ischemia-induced pathological angiogenesis called neovascularization during postnatal development. IL-10 deficiency resulted in significantly reduced pathological retinal angiogenesis. In contrast to the choroicapillaris where IL-10 interferes with macrophage influx, IL-10 did not prevent anti-angiogenic macrophages from migrating to the retina in response to hypoxia. Instead, IL-10 promoted retinal angiogenesis by altering macrophage angiogenic function, as macrophages from wild-type mice demonstrated increased vascular endothelial growth factor (VEGF) and nitric oxide (NO) compared to IL-10 deficient macrophages. IL-10 appears to directly affect macrophage responsiveness to hypoxia, as macrophages responded to hypoxia with increased levels of IL-10 and STAT3 phosphorylation as opposed to IL-10 deficient macrophages. Also, IL-10 deficient macrophages inhibited the proliferation of vascular endothelial cells in response to hypoxia while wild-type macrophages failed to do so. These findings suggest that hypoxia guides macrophage behavior to a pro-angiogenic phenotype via IL-10 activated pathways.
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PMID:Interleukin-10 promotes pathological angiogenesis by regulating macrophage response to hypoxia during development. 1885 82

Antioxidants specifically addressed to mitochondria have been studied to determine if they can decelerate senescence of organisms. For this purpose, a project has been established with participation of several research groups from Russia and some other countries. This paper summarizes the first results of the project. A new type of compounds (SkQs) comprising plastoquinone (an antioxidant moiety), a penetrating cation, and a decane or pentane linker has been synthesized. Using planar bilayer phospholipid membrane (BLM), we selected SkQ derivatives with the highest permeability, namely plastoquinonyl-decyl-triphenylphosphonium (SkQ1), plastoquinonyl-decyl-rhodamine 19 (SkQR1), and methylplastoquinonyldecyltriphenylphosphonium (SkQ3). Anti- and prooxidant properties of these substances and also of ubiquinonyl-decyl-triphenylphosphonium (MitoQ) were tested in aqueous solution, detergent micelles, liposomes, BLM, isolated mitochondria, and cell cultures. In mitochondria, micromolar cationic quinone derivatives were found to be prooxidants, but at lower (sub-micromolar) concentrations they displayed antioxidant activity that decreases in the series SkQ1=SkQR1>SkQ3>MitoQ. SkQ1 was reduced by mitochondrial respiratory chain, i.e. it is a rechargeable antioxidant. Nanomolar SkQ1 specifically prevented oxidation of mitochondrial cardiolipin. In cell cultures, SkQR1, a fluorescent SkQ derivative, stained only one type of organelles, namely mitochondria. Extremely low concentrations of SkQ1 or SkQR1 arrested H(2)O(2)-induced apoptosis in human fibroblasts and HeLa cells. Higher concentrations of SkQ are required to block necrosis initiated by reactive oxygen species (ROS). In the fungus Podospora anserina, the crustacean Ceriodaphnia affinis, Drosophila, and mice, SkQ1 prolonged lifespan, being especially effective at early and middle stages of aging. In mammals, the effect of SkQs on aging was accompanied by inhibition of development of such age-related diseases and traits as cataract, retinopathy, glaucoma, balding, canities, osteoporosis, involution of the thymus, hypothermia, torpor, peroxidation of lipids and proteins, etc. SkQ1 manifested a strong therapeutic action on some already pronounced retinopathies, in particular, congenital retinal dysplasia. With drops containing 250 nM SkQ1, vision was restored to 67 of 89 animals (dogs, cats, and horses) that became blind because of a retinopathy. Instillation of SkQ1-containing drops prevented the loss of sight in rabbits with experimental uveitis and restored vision to animals that had already become blind. A favorable effect of the same drops was also achieved in experimental glaucoma in rabbits. Moreover, the SkQ1 pretreatment of rats significantly decreased the H(2)O(2) or ischemia-induced arrhythmia of the isolated heart. SkQs strongly reduced the damaged area in myocardial infarction or stroke and prevented the death of animals from kidney ischemia. In p53(-/-) mice, 5 nmol/kgxday SkQ1 decreased the ROS level in the spleen and inhibited appearance of lymphomas to the same degree as million-fold higher concentration of conventional antioxidant NAC. Thus, SkQs look promising as potential tools for treatment of senescence and age-related diseases.
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PMID:An attempt to prevent senescence: a mitochondrial approach. 1915 10

Diabetic retinopathy--already the leading cause of irreversible blindness in working age Americans--is a rising threat as the diabetic population increases. Vision loss occurs due to retinal ischemia, retinal vascular exudation, intraocular hemorrhage, and ultimately, fibrotic complications. Optimal management of blood glucose levels and hypertension reduces the incidence and progression of retinopathy. Appropriate screening ensures early detection and management of diabetic retinopathy and reduces vision loss. Recent advances in our understanding of diabetic microvascular complications have led to new treatments that, along with refinements in laser and surgical techniques, are improving visual outcomes.
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PMID:Diabetic retinopathy: a growing concern in an aging population. 1925 82

Pathological angiogenesis is a hallmark of various ischemic diseases (insufficient vessel growth) but also of cancer and metastasis, inflammatory diseases, blindness, psoriasis or arthritis (excessive angiogenesis). In response to ischemia (reduced blood flow and oxygen supply), new blood vessels form in order to compensate for the lack of perfusion. This natural process could protect them from the consequences of atherosclerotic diseases (myocardial angina, infarction, hindlimb arteriopathy or stroke). However, neovessel formation is altered in many patients. A better understanding of the mechanisms of functional vessel formation is a pre-requisite to improving the treatment of ischemic pathologies. To this end, it is essential to create easily accessible animal models in which vessel formation can be both manipulated and studied. In this review, we will describe different angiogenic mouse models in the context of cardiovascular diseases, either in an ischemic context (hindlimb ischemia, heart ischemia, skin model) or in a non-ischemic context (plug and eye assay, wound healing, ovarian model). We will also discuss quantitative techniques for assessing angiogenesis in these assays.
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PMID:Mouse models to study angiogenesis in the context of cardiovascular diseases. 1927 76


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