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)

In 45 eyes of rhesus monkeys, five types of central retinal vascular occlusion were produced by lateral orbitotomy: group 1, central retinal vein occlusion (CRVO) alone; group 2, CRVO with simultaneous central retinal artery (CRA) occlusion; group 3, CRVO with transient clamping of the CRA for either 2 to 2 1/2 hours (group 3A) or 6 to 7 1/2 hours (group 3B); and group 4, CRVO with segmental retinal ischemia. The eyes were examined by fundus photography and fluorescein angiography for up to nine months. Group 1 developed venous stasis retinopathy (VSR) and group 3B hemorrhagic retinopathy (HR). In group 4 the ischemic and nonischemic segments of the retina developed segmental HR and VSR, respectively. Groups 2 and 3A developed neither VSR nor HR. Retinal capillary obliteration occurred in groups 2 and 3B and in the ischemic part of group 4, starting one to three weeks after the occlusion and progressing thereafter. These studies indicate that clinically co-called CRVO consists of two distinct entities: VSR and HR, with retinal ischemia playing an important role in the production of HR. On the basis of the present and other available information, the pathogenesis of CRVO was concluded to be multifactorial.
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PMID:Experimental retinal vascular occlusion. I. Pathogenesis of central retinal vein occlusion. 41 9

Pathogenesis of occlusion of the central retinal vessels, based on experimental and clinical findings, is discussed. It suggests that the so-called "central retinal vein occlusion" represents not only occlusion of the central retinal vein but also retinal arterial ischemia. Based on this pathogenesis the following terminology is recommended for central retinal vascular occlusion: (a) Ischemic retinopathy is due to occlusion of the central retinal artery. (b) Venous stasis retinopathy is due to occlusion of the central retinal vein alone. (c) Hemorrhagic retinopathy is due to occlusion of the central retinal vein associated with retinal ischemia. Clinical findings of (b) and (c) are compared which indicate that the two conditions are distinct entities and unfortunately so far have been dumped under a common heading of so-called "central retinal vein occlusions". Such a distinction is extremely important before any attempts are made to evaluate their natural history or effects of any therapy on them.
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PMID:So-called "central retinal vein occlusion". I. Pathogenesis, terminology, clinical features. 125 May 71

Thirty patients who suffered from ocular involvement caused by toxemia of pregnancy were examined ophthalmologically during the nine-year period between 1980 and 1988 at Osaka Medical Center and Research Institute for Maternal and Child Health. The ophthalmoscopic findings were divided into the following five categories: cotton wool patches (CWP), retinal hemorrhages (RH), hard exudates (HE), yellowish opaque foci (YOF) and serous retinal detachments (SRD). Although the first three types of findings were recognized as hypertensive retinopathy (Keith-Wagener III or IV), the last two were recognized as choroidal vascular damage. Based on the frequency of fundus findings, patients were divided into three types: R-type mainly suffered from retinal vascular occlusion (CWP), C-type mainly suffered from choroidal vascular occlusion (YOF, SRD), and R + C-type consisted of mixed vascular occlusion. The maximum systolic blood pressure of C-type patients was significantly lower than that of R-type. The maximum diastolic blood pressure of C-type patients was also significantly lower than those of R-type and R + C-type. There were five C-type cases with systolic blood pressure of less than 160 mmHg in which the choroidal ischemia was concluded not to be hypertensive choroidopathy but a specific alteration characterized by toxemia of pregnancy (hypercoagulopathy).
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PMID:[Retinochoroidal changes in toxemia of pregnancy with the relation to hypertensive retinopathy and choroidopathy]. 223 51

The authors observed three cases (6 eyes) of vaso-occlusive retinopathy associated with the lupus anticoagulant and the related antiphospholipid antibody anticardiolipin. The disease occurred in patients who had no definable autoimmune disease such as systemic lupus erythematosus (SLE) and was characterized by severe bilateral retinal vascular occlusion. There was profound visual loss from intraretinal ischemia as well as vitreous hemorrhage from preretinal neovascularization. Results of laboratory testing showed a prolonged partial thromboplastin time (PTT) in two patients, and the presence of the lupus anticoagulant in all. Treatment with panretinal photocoagulation appeared to stabilize the neovascularization. The role of systemic anticoagulation and immunosuppressive therapy is uncertain.
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PMID:Vaso-occlusive retinopathy associated with antiphospholipid antibodies (lupus anticoagulant retinopathy). 232

Central retinal artery occlusion occurs most commonly between the ages of 50 and 70 years, and nearly one-half (45%) of patients also have carotid artery disease. Other causes of vision-threatening vascular disease include atherosclerosis, embolism, hypertension, diabetes mellitus, and valvular disease. Symptoms vary, depending on the ocular structures involved. The patient's symptoms are an important clue to the diagnosis of peripheral or posterior retinal vascular occlusion, macular blood vessel disease, intravitreal hemorrhage, optic nerve ischemia, and ocular ischemic syndrome. The patient's ocular symptoms should lead to investigation for clinical signs of ocular vascular disease (eg, hemorrhage, "hard" or "soft" exudates, neovascularization, retinal edema, pallor, emboli, vessel narrowing, or atriovenous crossing changes).
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PMID:Ocular vascular disease: in-office primary care diagnosis. 843 37

Adenosine, an intercellular messenger that is a product of the metabolism of ATP, plays a major role in neuronal and vascular responses of the retina to alterations in oxygen delivery. Significant changes in adenosine concentration have been measured in the retina during both ischemia and during the subsequent reperfusion period which result in important, but complex, functional effects. Adenosine A1 receptor stimulation produces a protective effect during ischemia, whereas overstimulation of the A2a receptor has deleterious effects. The mechanisms underlying these findings have not been completely determined, but most likely are the result of alterations in excitotoxicity, gene expression, and blood flow. Paradoxically, prolonged increases in adenosine concentration may be injurious to the retina, a consequence of superoxide radical formation secondary to adenosine catabolism. Adenosine is a critical mediator of blood flow changes in response to ischemia. It is a significant component of the retina's compensatory hyperemic response to ischemia, hypoxia, and hypoglycemia. Increasing endogenous adenosine concentrations may be useful in ameliorating post-ischemic hypoperfusion. Overall, current evidence suggests that adenosine is a vital component of the endogenous retinal response to substrate deprivation. Additionally, in vitro studies provide strong evidence that adenosine is a mediator of the formation and effects of vascular endothelial growth factor, which in turn promotes neovascularization. Finally, the ability of the retina to develop an ischemia-tolerant state by ischemic preconditioning is an intriguing phenomenon that reveals yet another essential role for adenosine in the retina's endogenous response to ischemia. The experimental results described in this review suggest that continued investigation into the role of adenosine in the retina may lead to important clinical applications for adenosine-based therapies that could decrease the incidence of retinal damage in ischemic vasculopathies such as diabetes, glaucoma, and retinal vascular occlusion.
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PMID:The purine nucleoside adenosine in retinal ischemia-reperfusion injury. 1039 21

Diabetic retinopathy (DR) still remains the leading cause of blindness in the working population of Japan and western world, though therapies such as retinal photocoagulation and vitrectomy can be remarkably effective when administered at an appropriate stage in the disease process. Consequently, there is a need for further investigation of the pathogenesis of DR to develop better therapy. DR is characterized by gradually progressive alterations in the retinal microvasculature, leading to three fundamental morbidities: 1. vascular hyperpermeability, 2. vascular occlusion, and 3. neovascularization. Recent studies have revealed that hyperglycemia causes several metabolic disorders which cause DR directly or indirectly through the abnormal expression of cytokines including vascular endothelial growth factor (VEGF). In this study, we performed precise tests of the correlation between intraocular VEGF and the three fundamental changes in the diabetic retina mentioned above. Ultrastructural study of the human retina revealed that two major pathways are responsible for hyperpermeability of diabetic retinal vessels, i.e., intercellular or paracellular transport (opening of the tight junctions) and intracellular or transcellular transport (caveolae, intracytoplasmic vesicles, and fenestration). All these pathways were induced by intravitreal injection of VEGF. The major trigger of VEGF overexpression is tissue ischemia caused by vascular occlusion. However, the retinas from the eyes with background DR revealed increased expression of VEGF without apparent incidence of vascular occlusion. We have identified accumulation of advanced glycation end products (AGEs) in these retinas, and found that AGEs are a major stimulus for VEGF overexpression in background DR. Retinal vascular occlusion was caused by thrombus formation primarily in the capillary vessels. Thrombi mainly consisted of fibrin, platelets, and leucocytes in the early stage of their formation, and glial cells and macrophages were also involved in the later stage. The blood coagulation process plays an important role in fibrin formation in thrombi. The expression of tissue factor (TF), an initiator of extrinsic blood coagulation, was upregulated by VEGF in retinal vascular endothelial cells (REC). In addition, AGEs were also thrombogenic through the induction of TF expression and suppression of the expression of prostacyclin stimulating factor (PSF), which stimulate prostacyclin synthesis in vascular endothelial cells. These findings suggest that AGEs, VEGF, and TF could interact in a vicious circle because AGEs and VEGF could induce retinal vascular occlusion which results in further increase in VEGF expression. Intravitreal injection of VEGF could induce retinal neovascularization. VEGF stimulates vascular endothelial cell proliferation by binding to a specific receptor named kinase insert domain-containing receptor/fetal liver kinase (KDR/FIk-1, KDR). AGEs and basic fibroblast growth factor (bFGF) induced expression of KDR in REC, and a transcription factor Sp 1 was involved in this process. Since the expression of KDR as well as VEGF was already upregulated in the retinas with background DR, VEGF appeared to start to induce the proliferative changes long before the actual onset of proliferative DR. These findings indicated that VEGF and its receptor system plays a pivotal role all through the disease process of DR. We considered that amelioration of the activated VEGF and its receptor system could lead to the development of new therapy for DR. We have developed two novel methods to prevent retinal neovascularization by inhibiting VEGF and its receptor system. 1. An insulin sensitizing agent (troglitazone) inhibited proliferation, migration, and in vitro tube formation by REC as well as oxygen-induced retinal neovascularization in a mouse model. Thus, glycemic control by troglitazone could reduce the incidence of neovascularization in diabetic eyes. 2. (ABSTRACT TRUNCATED)
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PMID:[Cell biology of intraocular vascular diseases]. 1064 94

Diabetic retinopathy (DR) still remains the leading cause of blindness in the working population of Japan and western world, though therapies such as retinal photocoagulation and vitrectomy can be remarkably effective when administered at an appropriate stage in the disease process. Consequently, there is a need for further investigation of the pathogenesis of DR to develop better therapy. DR is characterized by gradually progressive alterations in the retinal microvasculature, leading to three fundamental morbidities: (1) vascular hyperpermeability, (2) vascular occlusion, and (3) neovascularization. Recent studies have revealed that hyperglycemia causes several metabolic disorders which cause DR directly or indirectly through the abnormal expression of cytokines including vascular endothelial growth factor (VEGF). In this study, we performed precise tests of the correlation between intraocular VEGF and the three fundamental changes in the diabetic retina mentioned above.Ultrastructural study of the human retina revealed that two major pathways are responsible for hyperpermeability of diabetic retinal vessels, ie intercellular or paracellular transport (opening of the tight junctions) and intracellular or transcellular transport (caveolae, intracytoplasmic vesicles, and fenestration). All these pathways were induced by intravitreal injection of VEGF. The major trigger of VEGF overexpression is tissue ischemia caused by vascular occlusion. However, the retinas from the eyes with background DR revealed increased expression of VEGF without apparent incidence of vascular occlusion. We have identified accumulation of advanced glycation end products (AGEs) in these retinas, and found that AGEs are a major stimulus for VEGF overexpression in background DR. Retinal vascular occlusion was caused by thrombus formation primarily in the capillary vessels. Thrombi mainly consisted of fibrin, platelets, and leucocytes in the early stage of their formation, and glial cells and macrophages were also involved in the later stage. The blood coagulation process plays an important role in fibrin formation in thrombi. The expression of tissue factor (TF), an initiator of extrinsic blood coagulation, was upregulated by VEGF in retinal vascular endothelial cells (REC). In addition, AGEs were also thrombogenic through the induction of TF expression and suppression of the expression of prostacyclin stimulating factor (PSF), which stimulate prostacyclin synthesis in vascular endothelial cells. These findings suggest that AGEs, VEGF, and TF could interact in a vicious circle because AGEs and VEGF could induce retinal vascular occlusion which results in further increase in VEGF expression.Intravitreal injection of VEGF could induce retinal neovascularization, VEGF stimulates vascular endothelial cell proliferation by binding to a specific receptor named kinase insert domain-containing receptor/fetal liver kinase (KDR/Flk-1, KDR). AGEs and basic fibroblast growth factor (bFGF) induced expression of KDR in REC, and a transcription factor Sp 1 was involved in this process. Since the expression of KDR as well as VEGF was already upregulated in the retinas with background DR, VEGF appeared to start to induce the proliferative changes long before the actual onset of proliferative DR. These findings indicated that VEGF and its receptor system plays a pivotal role all through the disease process of DR.We considered that amelioration of the activated VEGF and its receptor system could lead to the development of new therapy for DR. We have developed two novel methods to prevent retinal neovascularization by inhibiting VEGF and its receptor system. (1) An insulin sensitizing agent (troglitazone) inhibited proliferation, migration, and in vitro tube formation by REC as well as oxygen-induced retinal neovascularization in a mouse model. Thus, glycemic control by troglitazone could reduce the incidence of neovascularization in diabetic eyes. (ABSTRACT TRUNCATED)
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PMID:Cell biology of intraocular vascular diseases 1091 68

Retinal ischemia results in the loss of vision in a number of ocular diseases including acute glaucoma, diabetic retinopathy, hypertensive retinopathy and retinal vascular occlusion. Recent studies have shown that most of the neuronal death that leads to loss of vision results from apoptosis. XIAP-mediated gene therapy has been shown to protect a number of neuronal types from apoptosis but has never been assessed in retinal neurons following ischemic-induced cell death. We injected an adeno-associated viral vector expressing XIAP or GFP into rat eyes and 6 weeks later, rendered them ischemic by raising intraocular pressure. Functional analysis revealed that XIAP-treated eyes retained larger b-wave amplitudes than GFP-treated eyes up to 4 weeks post-ischemia. The number of cells in the inner nuclear layer (INL) and the thickness of the inner retina were significantly preserved in XIAP-treated eyes compared to GFP-treated eyes. Similarly, there was no significant reduction in optic nerve axon numbers in XIAP-treated eyes. There were also significantly fewer TUNEL (TdT-dUTP terminal nick end labeling) positive cells in the INL of XIAP-treated retinas at 24 h post-ischemia. Thus, XIAP-mediated gene therapy imparts both functional and structural protection to the retina after a transient ischemic episode.
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PMID:XIAP-mediated neuroprotection in retinal ischemia. 1630 1

Interferon (INF)-associated retinopathy occurs in 15-64% of INF-treated patients, transforming this complication into a significant risk for visual impairment. This retinopathy has been described as an ocular complication with a variable clinical course, usually benign and asymptomatic. The most common findings are hemorrhages and cotton wool spots. Atypical ocular side effects include branch or central retinal artery occlusion, central retinal vein occlusion, anterior ischemic optic neuropathy, optic disc edema, neovascular glaucoma and vitreous hemorrhage. Some case series suggest that in most cases the clinical course of the disease is benign, asymptomatic and without long-term consequences and therefore do not recommend any specific treatment; they only recommend the discontinuation of INF in patients with severe manifestations or risk factors such as hypertension or diabetes mellitus. The case reported here presents an atypical manifestation of INF-associated retinopathy consisting of a mixed retinal vascular occlusion (arterial and venous), associated with severe occlusive inflammatory microangiopathy with extensive retinal damage by ischemia and a torpid clinical course despite suspension of treatment. These varieties of occlusive vascular events have not yet been found simultaneously in the literature and neither with an unfavorable clinical course. Although the clinical course of INF-associated retinopathy in most cases is asymptomatic, there may be complications with risk to vision, which is less common. The magnitude and severity of the consequences associated with INF therapy are to be determined in prospective further studies.
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PMID:Mixed vascular occlusion in a patient with interferon-associated retinopathy. 2132 40


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