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Sample records for acute central retinal

  1. Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis.

    PubMed

    Fong, Choong Yi; Aye, Aye Mya Min; Peyman, Mohammadreza; Nor, Norazlin Kamal; Visvaraja, Subrayan; Tajunisah, Iqbal; Ong, Lai Choo

    2014-04-01

    We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease. PMID:24378951

  2. Acute Central Retinal Vein Occlusion Secondary to Reactive Thrombocytosis after Splenectomy

    PubMed Central

    Oncel Acir, Nursen; Borazan, Mehmet

    2014-01-01

    The diagnosis and treatment of central retinal vein occlusion was reported in a young patient. Central retinal vein occlusion was probably related to secondary to reactive thrombocytosis after splenectomy. The patient was treated with steroids for papilledema and administered coumadin and aspirin. The symptoms resolved, and the findings returned to normal within three weeks. Current paper emphasizes that, besides other well-known thrombotic events, reactive thrombocytosis after splenectomy may cause central retinal vein occlusion, which may be the principal symptom of this risky complication. Thus, it can be concluded that followup for thrombocytosis and antithrombotic treatment, when necessary, are essential for these cases. PMID:25276452

  3. [Acute retinal necrosis].

    PubMed

    Lucke, K; Reinking, U; el-Hifnawi, E; Dennin, R H; Laqua, H

    1988-12-01

    The authors report on three patients with acute retinal necrosis who were treated with the virostatic agent Acyclovir and who underwent vitreoretinal surgery with silicone oil filling for total retinal detachment. In two eyes the retina was reattached, but useful vision was only preserved in one patient. Titers from blood and the vitreous, as well as microscopic findings in retinal biopsies, support the view that the necrosis is caused by a herpes simplex virus infection. After therapy with Acyclovir was instituted no further progression on the necrosis was observed. However, the development of retinal detachment could not be prevented. Early diagnosis and antiviral therapy are essential to improve the otherwise poor prognosis in this rare syndrome. PMID:3221657

  4. ACUTE RETINAL ARTERIAL OCCLUSIVE DISORDERS

    PubMed Central

    Hayreh, Sohan Singh

    2011-01-01

    The initial section deals with basic sciences; among the various topics briefly discussed are the anatomical features of ophthalmic, central retinal and cilioretinal arteries which may play a role in acute retinal arterial ischemic disorders. Crucial information required in the management of central retinal artery occlusion (CRAO) is the length of time the retina can survive following that. An experimental study shows that CRAO for 97 minutes produces no detectable permanent retinal damage but there is a progressive ischemic damage thereafter, and by 4 hours the retina has suffered irreversible damage. In the clinical section, I discuss at length various controversies on acute retinal arterial ischemic disorders. Classification of acute retinal arterial ischemic disorders These are of 4 types: CRAO, branch retinal artery occlusion (BRAO), cotton wools spots and amaurosis fugax. Both CRAO and BRAO further comprise multiple clinical entities. Contrary to the universal belief, pathogenetically, clinically and for management, CRAO is not one clinical entity but 4 distinct clinical entities – non-arteritic CRAO, non-arteritic CRAO with cilioretinal artery sparing, arteritic CRAO associated with giant cell arteritis (GCA) and transient non-arteritic CRAO. Similarly, BRAO comprises permanent BRAO, transient BRAO and cilioretinal artery occlusion (CLRAO), and the latter further consists of 3 distinct clinical entities - non-arteritic CLRAO alone, non-arteritic CLRAO associated with central retinal vein occlusion and arteritic CLRAO associated with GCA. Understanding these classifications is essential to comprehend fully various aspects of these disorders. Central retinal artery occlusion The pathogeneses, clinical features and management of the various types of CRAO are discussed in detail. Contrary to the prevalent belief, spontaneous improvement in both visual acuity and visual fields does occur, mainly during the first 7 days. The incidence of spontaneous visual

  5. Experimental occlusion of the central artery of the retina. IV: Retinal tolerance time to acute ischaemia.

    PubMed Central

    Hayreh, S. S.; Weingeist, T. A.

    1980-01-01

    Ophthalmoscopic, fluorescein angiographic, electrophysiological, and morphological studies on 63 eyes of rhesus monkeys with acute transient experimental occlusion of the central artery of the retina (OCAR) showed that the retina suffered irreparable damage after ischaemia of 105 minutes but recovered well after ischaemia of 97-98 minutes. The tolerance time of the brain to acute transient ischaemia is many times shorter than that of the retina. The metabolism of ischaemic neurones (in the retina and brain) is discussed with a view to explaining this difference, and also the various factors possibly responsible for the retina's longer tolerance to ischaemia, as compared to the brain. PMID:7426553

  6. Prevalent misconceptions about acute retinal vascular occlusive disorders.

    PubMed

    Hayreh, Sohan Singh

    2005-07-01

    Acute retinal vascular occlusive disorders collectively constitute one of the major causes of blindness or seriously impaired vision, and yet there is marked controversy on their pathogeneses, clinical features and particularly their management. This is because the subject is plagued by multiple misconceptions. These include that: (i) various acute retinal vascular occlusions represent a single disease; (ii) estimation of visual acuity alone provides all the information necessary to evaluate visual function; (iii) retinal venous occlusions are a single clinical entity; (iv) retinal vein occlusion is essentially a disease of the elderly and is not seen in the young; (v) central retinal vein occlusion (CRVO) is one disease; (vi) fluorescein fundus angiography is the best test to differentiate ischemic from nonischemic CRVO; (vii) the site of occlusion in CRVO is invariably at the lamina cribrosa; (viii) clinical picture of CRVO is often due to compression or strangulation of the central retinal vein (CRV) in the lamina cribrosa and not its occlusion; (ix) an eye can develop both CRVO and central retinal artery occlusion (CRAO) simultaneously; (x) every eye with CRVO is at risk of developing neovascular glaucoma; (xi) lowering intraocular pressure (IOP) helps to improve retinal circulation in an eye with CRVO; (xii) every patient with retinal vein occlusion should have complete hematologic and coagulation evaluation; (xiii) the natural history of CRVO does not usually involve spontaneous visual improvement; (xiv) management of CRVO is similar to that of venous thrombosis anywhere else in the body, i.e. with aspirin and/or anti-coagulants; (xv) fibrinolytic agents can dissolve an organized thrombus in the CRV; (xvi) it is beneficial to lower blood pressure in patients with CRVO; (xvii) panretinal photocoagulation used in ischemic retinal venous occlusive disorders has no deleterious side-effects; (xviii) glaucoma or ocular hypertension can cause branch retinal vein

  7. NONICHEMIC CENTRAL RETINAL VEIN OCCLUSION ASSOCIATED WITH HEREDITARY THROMBOPHYLIA.

    PubMed

    Fişuş, Andreea Dana; Pop, Doina Suzana; Rusu, Monica Blanka; Vultur, Florina; Horvath, Karin Ursula

    2015-01-01

    Retinal vein occlusion (RVO) is the second most common retinal vein disease with significant visual loss via thrombus or compression of vein wall. Thrombophilia is the predisposition to vascular thrombosis with the existence of genetic defect that leads to blood hypercoagulability. This report describes the case of a 55 year old male patient, with an active life who presented himself at the emergency room with acute visual lose, insidious and progressive visual field constriction, without any known history of neurological or vascular diseases. The examinations revealed unilateral optic nerve head edema, the fluorescein angiography was specific for nonischemic central retinal vein occlusion CRVO complicated with macular edema. Blood examinations has emphasized the presence of the heterozygous mutation A1298C in the methylenetetrahydrofolate reductase gene (MTHFR), the only one presented from the thrombophilia screen panel and a slightly elevated cholesterol level. During the follow-up period, the patient received anti-VEGF treatment (Bevacizumab, 3x 0.1 ml intravitreal injections) with improved visual acuity and amendment of macular edema. The complex etiology calls for interdisciplinary approach to determine better the cause of this ophthalmological disease. Although studies have found a correlation between some thrombophilia mutations and retinal vein occlusion, more studies that contain a larger number of patients are necessary in order to determine the final role of these gene variants. PMID:26978887

  8. Central retinal vein occlusion and pseudoexfoliation syndrome

    PubMed Central

    Karagiannis, Dimitrios; Kontadakis, Georgios A; Klados, Nektarios E; Tsoumpris, Ioannis; Kandarakis, Artemios S; Parikakis, Efstratios A; Georgalas, Ilias; Tsilimbaris, Miltiadis K

    2015-01-01

    Purpose The purpose of this study was to investigate the existence of pseudoexfoliation syndrome (PXF) as a risk factor for the development of central retinal vein occlusion (CRVO). Methods This was a retrospective, comparative study of the prevalence of pseudoexfoliation in three groups of patients: 48 patients with CRVO, 164 patients with branch retinal vein occlusion (BRVO), and 70 control patients (70 eyes). All patients were phakic and had no previous diagnosis of glaucoma. Patients were matched in terms of age and systemic hypertension. All patients had normal intraocular pressure (IOP) at presentation (defined as less than or equal to 21 mmHg). Results In the CRVO group, 14 out of 48 patients were diagnosed as having PXF (29.17%). In the BRVO group, 14 out of 164 patients had PXF (8.5%), and in the control group, six out of 70 patients had PXF (8.6%). Differences of percentage between groups were statistically significant (P<0.001, χ2 test). When comparing patient subgroup with ischemic CRVO with subgroup with non-ischemic CRVO, we found that in the ischemic CRVO group, 13 out of 27 patients were diagnosed as having PXF (48.15%), and in the non-ischemic CRVO group, one out of 21 patients was diagnosed as having PXF (4.7%; P<0.001, χ2 test). The relative odds of having CRVO in patients with PXF versus patients without PXF were 4.406 (confidence interval [CI], 2.03–9.54). Conclusion PXF and CRVO, especially ischemic, are strongly associated in our study. Our results indicate that PXF might be an independent factor for CRVO, as it is related with CRVO independently from glaucoma. PMID:26056437

  9. Acute Variations in Retinal Vascular Oxygen Content in a Rabbit Model of Retinal Venous Occlusion

    PubMed Central

    Saati, Saloomeh; Martin, Gabriel; Chader, Gerald; Humayun, Mark S.

    2012-01-01

    Purpose To study the variation in intravascular oxygen saturation (oximetry) during an acute retinal vein occlusion (RVO) using hyperspectral computed tomographic spectroscopy based oximetry measurements. Methods Thirty rabbits were dilated and anesthetized for experiments. Baseline oximetry measurements were made using a custom-made hyperspectral computed tomographic imaging spectrometer coupled to a fundus camera. RVO were induced using argon green laser following an intravenous injection of Rose Bengal. RVO induction was confirmed by fluorescein angiography. Retinal oximetry measurements were repeated in arterial and venous branches one hour after RVO induction and up to 4 weeks afterwards. Comparison of retinal oximetry before and after vein occlusion was made using the Student T-test. Results One hour after RVO induction, we observed statistically significant reductions in the intravascular oxygen saturation in temporal retinal arteries (85.1±6.1% vs. 80.6±6.6%; p<0.0001) and veins (71.4±5.5% vs. 64.0±4.7%; p<0.0001). This decrease was reversible in animals that spontaneously recannulated the vein occlusion. There were no statistically significant differences in oxygen saturation in the nasal control arteries and veins before and after temporal vein RVO induction. Conclusions We demonstrate, for the first time, acute changes in the intravascular oxygen content of retinal vessels 1 hour after RVO. These changes are reversible upon spontaneous recannulation of retinal vessels. This study demonstrates that hyperspectral computer tomographic spectroscopy based oximetry can detect physiological variations in intravascular retinal oxygen saturation. The study also provides the first qualitative and quantitative evidence of the variation in retinal vascular oxygen content directly attributable to an acute retinal vein occlusion. PMID:23185567

  10. Retino-choroidal ischemia in central retinal vein occlusion

    PubMed Central

    Hussain, Nazimul; Hussain, Anjli

    2014-01-01

    A 41-year-old gentleman with insulin dependent diabetes had decreased vision in the right eye due to non-ischemic central retinal vein occlusion with macular edema. One month following intravitreal ranibizumab, he developed retino-choroidal ischemia with further loss of vision. Authors show the fluorescein angiographic transition from non-ischemic central retinal vein occlusion to retino-choroidal ischemia. PMID:25473353

  11. [Acute bilateral impaired vision with central scotoma in an 11-year-old boy].

    PubMed

    Pollithy, S; Ach, T; Schaal, K B; Dithmar, S

    2012-09-01

    This article presents a case of acute bilateral impaired vision and central scotoma in an 11-year-old boy. Looking directly into a laser beam of a laser pointer for only a few seconds can cause retinal damage in the form of lesions of the retinal pigment epithelium and the photoreceptor layer, up to retinal hemorrhage. Patients often complain about impaired vision and a central scotoma of the affected eye. PMID:22740016

  12. Clinical Manifestation of Self-Limiting Acute Retinal Necrosis

    PubMed Central

    Brydak-Godowska, Joanna; Borkowski, Piotr; Szczepanik, Szymon; Moneta-Wielgoś, Joanna; Kęcik, Dariusz

    2014-01-01

    Background The purpose of this paper was to present a case series of self-limiting, peripheral acute retinal necrosis and to demonstrate efficacy of treatment with valacyclovir in patients resistant to acyclovir. The diagnosis was made on ophthalmoscopic examination and positive serum tests for herpes viruses. Material/Methods Ten patients (6F and 4M) aged 19–55 years were diagnosed and treated for self-limiting acute retinal necrosis (ARN). The following endpoints were reported: visual outcomes, clinical features, disease progression, treatment, and complications. Patients received only symptomatic treatment because they did not consent to vitreous puncture. Results Peripheral, mild retinitis was diagnosed in all eyes at baseline. Initially, all patients were treated with systemic acyclovir (800 mg, 5 times a day), prednisone (typically 40–60 mg/day), and aspirin in an outpatient setting. In 6 patients, treatment was discontinued at 6 months due to complete resolution of the inflammatory process. Four patients with immune deficiency showed signs and symptoms of chronic inflammation. Two patients did not respond to acyclovir (2 non-responders); however, those patients were successfully treated with valacyclovir. Complete resolution of inflammatory lesions was observed in 8 patients. In 2 patients, the disease progressed despite treatment – 1 female patient after kidney transplant who stopped the prescribed medications, and 1 male patient with SLE and antiphospholipid syndrome who experienced breakthrough symptoms on-treatment. He died due to cerebral venous sinus thrombosis. Neurological complications (encephalitis and meningitis) were observed in 2 female patients. Prophylactic laser photocoagulation was performed in 1 subject. Conclusions A series of cases of self-limiting acute retinal necrosis (ARN) is presented. This clinical form of ARN can resemble toxoplasmic retinitis in some cases. Oral antiviral medications provide an effective alternative to

  13. Emerging concepts in the management of acute retinal necrosis.

    PubMed

    Wong, Robert William; Jumper, J Michael; McDonald, H Richard; Johnson, Robert N; Fu, Arthur; Lujan, Brandon J; Cunningham, Emmett T

    2013-05-01

    Acute retinal necrosis (ARN), also known as Kirisawa-type uveitis, is an uncommon condition caused by infection of the retina by one of the herpes family of viruses, most typically varicella zoster virus or herpes simplex virus and less commonly cytomegalovirus. Clinical diagnosis can be challenging and is often aided by PCR-based analysis of ocular fluids. Treatment typically involves extended use of one or more antiviral agents. Long term retinal detachment risk is high. We review the literature on ARN and present an approach to the diagnosis and management of this serious condition. PMID:23235944

  14. Central retinal vein occlusion in a migraine patient.

    PubMed

    Benninger, Felix; Saban, Tal; Steiner, Israel

    2015-11-01

    We describe a 31-year-old woman with a history of migraines without aura, who presented to our emergency department due to a monocular visual disturbance. This was misdiagnosed as being related to her migraine, however, it was subsequently found to be caused by a central retinal vein occlusion. Patients suffering from migraine can experience visual disturbances in the form of auras. The neuropathological basis for this phenomenon is thought to be a spreading depression in the visual cortex, causing a hemifield active visual phenomenon. Missing the diagnosis of central retinal vein occlusion is common, especially in the setting of an initially normal fundoscopy examination. PMID:26115899

  15. Dermatomyositis-Related Nonischemic Central Retinal Vein Occlusion.

    PubMed

    Wang, Yvonne; Morgan, Michael L; Espino Barros Palau, Angelina; Lee, Andrew G; Foroozan, Rod

    2015-09-01

    A 25-year-old woman with dermatomyositis suffered a right central retinal vein occlusion (CRVO) with visual acuity of 20/40. Examination of the right eye showed vitreous cells, suggesting inflammation of the central retinal vein leading to a CRVO as the presumed mechanism. She was admitted to hospital, and extensive evaluation was negative. She was maintained on corticosteroids to manage her dermatomyositis. One month later, she had macular edema and elevated intraocular pressure. Both resolved with dorzolamide, timolol, and intravitreal bevacizumab, and vision returned to 20/20 in the right eye. PMID:25815857

  16. Central Retinal Vein Occlusion in a Patient with Retinal Vasculitis and Crohn's Disease

    PubMed Central

    Figueiredo, Lígia; Rothwell, Renata; Brandão, Arnaldo

    2014-01-01

    The authors report a rare case of a 47-year-old woman with Crohn's disease (CD) who presented with retinal vasculitis and central retinal vein occlusion (CRVO) during remission. The patient complained of sudden painless visual loss in her left eye (OS). Ophthalmologic evaluation revealed a best corrected visual acuity (BCVA) of 20/20 in the right eye and hand movements in OS. Ophthalmoscopy and fluorescein angiography of OS showed signs of nonischemic CRVO and extensive vasculitis. She was treated with oral prednisolone, mercaptopurine, and intravitreal bevacizumab in OS. After 1 month of treatment, VA of OS improved to 5/10 and after 1 year it was 10/10 with complete resolution of retinal vasculitis and nonischemic CRVO. PMID:25506451

  17. Architecture of retinal projections to the central circadian pacemaker.

    PubMed

    Fernandez, Diego Carlos; Chang, Yi-Ting; Hattar, Samer; Chen, Shih-Kuo

    2016-05-24

    The suprachiasmatic nucleus (SCN) receives direct retinal input from the intrinsically photosensitive retinal ganglion cells (ipRGCs) for circadian photoentrainment. Interestingly, the SCN is the only brain region that receives equal inputs from the left and right eyes. Despite morphological assessments showing that axonal fibers originating from ipRGCs cover the entire SCN, physiological evidence suggests that only vasoactive intestinal polypeptide (VIP)/gastrin-releasing peptide (GRP) cells located ventrally in the SCN receive retinal input. It is still unclear, therefore, which subpopulation of SCN neurons receives synaptic input from the retina and how the SCN receives equal inputs from both eyes. Here, using single ipRGC axonal tracing and a confocal microscopic analysis in mice, we show that ipRGCs have elaborate innervation patterns throughout the entire SCN. Unlike conventional retinal ganglion cells (RGCs) that innervate visual targets either ipsilaterally or contralaterally, a single ipRGC can bilaterally innervate the SCN. ipRGCs form synaptic contacts with major peptidergic cells of the SCN, including VIP, GRP, and arginine vasopressin (AVP) neurons, with each ipRGC innervating specific subdomains of the SCN. Furthermore, a single SCN-projecting ipRGC can send collateral inputs to many other brain regions. However, the size and complexity of the axonal arborizations in non-SCN regions are less elaborate than those in the SCN. Our results provide a better understanding of how retinal neurons connect to the central circadian pacemaker to synchronize endogenous circadian clocks with the solar day. PMID:27162356

  18. [Sudden left-sided vision loss. Occlusion of the left central retinal artery].

    PubMed

    Stebler, J; Oechslin, E; Bernasconi, P; Greminger, P

    2001-05-23

    A 77 year old female patient was admitted to our hospital because of a rapid onset left-sided visual loss. Occlusion of the left central retinal artery was confirmed by the consultant ophthalmologist. The patient was further evaluated to exclude a thromboembolic event. Chest x-ray was consistent with pulmonary hypertension. Doppler echocardiography revealed a secundum atrial septal defect with a bi-directional shunt. In this 77 year old patient, arterio-arterial embolism from atherosclerotic plaques is the most probable cause of her central retinal artery occlusion. Yet, paradoxical embolism might be another reason for acute visual loss in this setting, which, however, is difficult to confirm definitively. PMID:11441708

  19. Irreversible visual loss and optic nerve dysfunction associated with central retinal vein occlusion in Waldenstrom Macroglobulinemia.

    PubMed

    Fadilah, S A W; Muhaya, M; Azlin, I

    2007-10-01

    Irreversible optic nerve dysfunction associated with central retinal vein occlusion (CRVO) is an unusual but important complication of Waldenstrom Macroglobulinemia (WM). Acute visual loss in CRVO is mainly due the severe macular oedema. However, ischaemic optic neuropathy needs to be considered in patients with CRVO when, (i) there is a relative afferent papillary defect and central scotoma, (ii) the visual acuity is not consistent with the retinal pathology, and (iii) the visual defects persisted despite resolution of macular oedema following treatment of the hyperviscosity state. The ischaemic type of CRVO is associated with a poor visual prognosis and the presenting visual acuity has a prognostic role. We report the first description of irreversible unilateral optic nerve damage associated with CRVO in a patient with WM. PMID:18551947

  20. Acute retinal necrosis secondary to herpes simplex virus type 2 with preexisting chorioretinal scarring.

    PubMed

    Moesen, Ingemarie; Khemka, Sneh; Ayliffe, William

    2008-01-01

    Acute retinal necrosis in children is a devastating disease that requires early diagnosis and treatment. The authors describe a rarely reported case of bilateral acute retinal necrosis in a child caused by neonatal herpes simplex virus type 2, where the presence of previous chorioretinal scarring made diagnosis challenging. PMID:18286969

  1. Acute unilateral vision loss with optic disc oedema in retinitis pigmentosa.

    PubMed

    Patil-Chhablani, Preeti; Tyagi, Mudit; Kekunnaya, Ramesh; Narayanan, Raja

    2015-01-01

    A 36-year-old woman presented with acute vision loss and was found to have disc oedema and retinitis pigmentosa (RP). She presented with a history of acute, painless vision loss in her left eye over a period of 10 days. Her best-corrected visual acuity was 20/50, N6 in the right eye (OD) and 20/160, N6 in the left eye (OS). She was found to have a swollen optic disc and the examination of her fundus showed changes suggestive of RP. The diagnosis of RP was confirmed by electroretinogram, and after ruling out demyelinating changes in the central nervous system and other possible infectious causes of papillitis, she was treated with intravenous steroids followed by a course of oral steroid therapy. Following treatment, her visual acuity improved to 20/60. Acute vision loss may occur in patients with RP and prompt steroid therapy may result in partial visual recovery. PMID:26240107

  2. Cytomegalovirus retinitis after central retinal vein occlusion in a patient on systemic immunosuppression: does venooclusive disease predispose to cytomegalovirus retinitis in patients already at risk?

    PubMed Central

    Welling, John D; Tarabishy, Ahmad B; Christoforidis, John B

    2012-01-01

    Cytomegalovirus (CMV) retinitis remains the most common opportunistic ocular infection in immunocompromised patients. Patients with immunocompromising diseases, such as acquired immunodeficiency syndrome, inherited immunodeficiency states, malignancies, and those on systemic immunosuppressive therapy, are known to be at risk. Recently, it has been suggested that patients undergoing intravitreal injection of immunosuppressive agents may also be predisposed. One previous case report speculated that there may be an additional risk for CMV retinitis in acquired immunodeficiency syndrome patients with venoocclusive disease. This case study presents a case of CMV retinitis following central retinal vein occlusion in a patient on systemic immunosuppressants. PMID:22570539

  3. Increase in Central Retinal Edema after Subthreshold Diode Micropulse Laser Treatment of Chronic Central Serous Chorioretinopathy

    PubMed Central

    Gawęcki, Maciej

    2015-01-01

    Purpose. Subthreshold diode micropulse laser (SDM) treatment is believed to be safe method of treating clinical entities involving retinal edema. We present a case of serous edematous reaction of the retina to SDM treatment. Methods. Case report. Results. A patient with chronic central serous chorioretinopathy (CSCR) was treated with SDM Yellow multispot laser. Procedure had been preceded by careful titration of the laser power, which after achieving of the threshold parameter was decreased by 50%. The follow-up visit two days after treatment revealed significant central retinal edema and subretinal fluid. Fundus autofluorescence image showed thermal reaction from the RPE in the form of small spots of hyperfluorescence corresponding to the laser multispot pattern used for treatment. Retinal edema resolved after topical bromfenac and single intravitreal bevacizumab injection. Slight pigmentary reaction from the RPE persisted. Conclusion. In the treatment of CSCR, there is a need to significantly reduce threshold SDM power parameters or simply use very low power without titration. PMID:26180649

  4. Antiviral selection in the management of acute retinal necrosis

    PubMed Central

    Tam, Patrick MK; Hooper, Claire Y; Lightman, Susan

    2010-01-01

    There is no consensus on the optimal antiviral regimen in the management of acute retinal necrosis, a disease caused by herpetic viruses with devastating consequences for the eye. The current gold standard is based on retrospective case series. Because the incidence of disease is low, few well-designed, randomized trials have evaluated treatment dosage and duration. Newer oral antiviral agents are emerging as alternatives to high-dose intravenous acyclovir, avoiding the need for inpatient intravenous treatment. Drug resistance is uncommon but may also be difficult to identify. Antiviral drugs have few side effects, but special attention needs to be paid to patients who have underlying renal disease, are pregnant or are immunocompromised. PMID:20169044

  5. Ocular neovascularization in eyes with a central retinal artery occlusion or a branch retinal artery occlusion

    PubMed Central

    Mason, John O; Patel, Shyam A; Feist, Richard M; Albert, Michael A; Huisingh, Carrie; McGwin, Gerald; Thomley, Martin L

    2015-01-01

    Purpose To investigate the ocular neovascularization (ONV) rate in eyes with a branch retinal artery occlusion (BRAO) or a central retinal artery occlusion (CRAO), and to study factors that may influence the ONV rate secondary to CRAO. Methods This was a retrospective case series of consecutive patients (286 total eyes: 83 CRAOs and 203 BRAOs) who were diagnosed with a retinal artery occlusion from 1998 to 2013 at the Retina Consultants of Alabama and University of Alabama at Birmingham, Birmingham, AL, USA. Generalized estimating equations were used to evaluate the association between hypothesized risk factors and ONV development. Results Twelve (14.5%) of the 83 eyes with a CRAO developed ONV. Eleven of 12 eyes (91.7%) had iris neovascularization, ten of 12 eyes (83.3%) had neovascular glaucoma, and two of 12 eyes (16.7%) had neovascularization of the optic disc. The average time for ONV development secondary to CRAO was 30.7 days, ranging from the date of presentation to 137 days. Only two (<1.0%) of the 203 eyes with a BRAO developed iris neovascularization. Diabetes mellitus type 2 was a risk factor for ONV development following a CRAO with an adjusted odds ratio of 5.2 (95% confidence interval: 1.4–19.8) (P=0.02). Conclusion ONV is an important complication of CRAO and is a less-frequent complication of BRAO. Patients with a CRAO, especially those with diabetes mellitus type 2, should be closely monitored for the first 6 months for ONV. PMID:26089631

  6. Retinal Electrophysiology Is a Viable Preclinical Biomarker for Drug Penetrance into the Central Nervous System

    PubMed Central

    Charng, Jason; He, Zheng; Vingrys, Algis J.; Fish, Rebecca L.; Gurrell, Rachel; Bui, Bang V.; Nguyen, Christine T.

    2016-01-01

    Objective. To examine whether retinal electrophysiology is a useful surrogate marker of drug penetrance into the central nervous system (CNS). Materials and Methods. Brain and retinal electrophysiology were assessed with full-field visually evoked potentials and electroretinograms in conscious and anaesthetised rats following systemic or local administrations of centrally penetrant (muscimol) or nonpenetrant (isoguvacine) compounds. Results. Local injections into the eye/brain bypassed the blood neural barriers and produced changes in retinal/brain responses for both drugs. In conscious animals, systemic administration of muscimol resulted in retinal and brain biopotential changes, whereas systemic delivery of isoguvacine did not. General anaesthesia confounded these outcomes. Conclusions. Retinal electrophysiology, when recorded in conscious animals, shows promise as a viable biomarker of drug penetration into the CNS. In contrast, when conducted under anaesthetised conditions confounds can be induced in both cortical and retinal electrophysiological recordings. PMID:27239335

  7. Central retinal vein occlusion: modifying current treatment protocols.

    PubMed

    Ashraf, M; Souka, A A R; Singh, R P

    2016-04-01

    Central retinal vein occlusion (CRVO) is a common retinal vascular disorder that can result in severe visual acuity loss. The randomized control study, CRUISE, helped establish anti-VEGFs as the standard of care in cases with CRVO. The extension studies for CRUISE; HORIZON and RETAIN showed that not all visual gains are maintained beyond the first year. In addition, patients showed different behavior patterns; with some patients showing complete response with few recurrences, whereas others showed partial or even no response with multiple recurrences. Long-term follow-up demonstrated that patients responding poorly to anti-VEGFs tended to do so early in the course of treatment. It also demonstrated the effectiveness of a pro re nata (PRN) protocol for improving vision and maintaining these gains over long-term follow-ups. The SHORE study further illustrated this point by demonstrating that there were minimal differences in visual outcomes between patients receiving monthly injections and patients being treated PRN. In this review we analyzed the data from the major randomized clinical trials (RCT) that looked at anti-VEGFs as the primary treatment modality in patients with CRVO (CRUISE and the extension studies HORIZON and RETAIN for ranibizumab as well as GALILEO and COPERNICUS for aflibercept). In addition, we looked at SCORE and GENEVA to help determine whether there is a place for steroids as a first line therapy in current treatment practice. We then explored alternative treatment regimens such as laser therapy and switching between anti-VEGF agents and/or steroids for non or partially responding patients. Finally, we propose a simplified modified treatment algorithm for patients with CRVO for better long-term outcomes in all types of responders. PMID:26869163

  8. Central retinal artery pressure and carotid artery stenosis

    PubMed Central

    SUN, RAN; PENG, XIAO-YAN; YOU, QI-SHENG; JIAO, LI-QUN; JONAS, JOST B.

    2016-01-01

    The central retinal artery (CRA), which can be non-invasively examined with ophthalmoscopy, may be regarded as an extracranial part of the cerebrovascular system. Assessment of CRA pressure may be of help in assessing the impediment of the intracranial blood circulation in patients with a carotid artery stenosis (CAS). The aim of this study was to explore the potential associations between diastolic central retinal artery pressure (diastCRAP) and CAS. The prospective longitudinal clinical observational study included patients with CAS and a control group without CAS. diastCRAP was assessed using ophthalmodynamometry. The study group consisted of 95 patients with CAS (50 of whom had >75%CAS and underwent surgery; the surgical study group) and a control group of 64 individuals without CAS. In all study participants, a lower diastCRAP was significantly associated with a higher degree of CAS (P<0.001). Multivariate analysis indicated that a higher CAS degree was significantly (correlation coefficient: r=0.75) associated with a higher brachial diastolic blood pressure (P<0.001) and lower diastCRAP (P<0.001). Within the surgical study group at the baseline of the study, diastCRAP was significantly lower at the surgical side than at the contralateral side (P=0.02). The diastCRAP on the surgical side increased significantly (P<0.001) after surgery. In the surgical study group at baseline, diastCRAP on the surgical side was not significantly associated with brachial diastolic blood pressure (P=0.22), whereas after surgery, diastCRAP was significantly associated with brachial diastolic blood pressure (P=0.001). DiastCRAP was found to be significantly and linearly correlated with the degree of CAS in intra-individual inter-eye, inter-individual and intra-individual follow-up comparisons. The strong and linear association between diastCRAP and the degree of CAS suggest that diastCRAP should be explored further for use as an indicator of cerebrovascular status. PMID:26998005

  9. A method and technical equipment for an acute human trial to evaluate retinal implant technology

    NASA Astrophysics Data System (ADS)

    Hornig, Ralf; Laube, Thomas; Walter, Peter; Velikay-Parel, Michaela; Bornfeld, Norbert; Feucht, Matthias; Akguel, Harun; Rössler, Gernot; Alteheld, Nils; Lütke Notarp, Dietmar; Wyatt, John; Richard, Gisbert

    2005-03-01

    This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 µm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration.

  10. A method and technical equipment for an acute human trial to evaluate retinal implant technology.

    PubMed

    Hornig, Ralf; Laube, Thomas; Walter, Peter; Velikay-Parel, Michaela; Bornfeld, Norbert; Feucht, Matthias; Akguel, Harun; Rössler, Gernot; Alteheld, Nils; Lütke Notarp, Dietmar; Wyatt, John; Richard, Gisbert

    2005-03-01

    This paper reports on methods and technical equipment to investigate the epiretinal stimulation of the retina in blind human subjects in acute trials. Current is applied to the retina through a thin, flexible microcontact film (microelectrode array) with electrode diameters ranging from 50 to 360 microm. The film is mounted in a custom-designed surgical tool that is hand-held by the surgeon during stimulation. The eventual goal of the work is the development of a chronically implantable retinal prosthesis to restore a useful level of vision to patients who are blind with outer retinal degenerations, specifically retinitis pigmentosa and macular degeneration. PMID:15876648

  11. Acute and Chronic Hyperglycemia Elicit JIP1/JNK-Mediated Endothelial Vasodilator Dysfunction of Retinal Arterioles

    PubMed Central

    Hein, Travis W.; Xu, Wenjuan; Xu, Xin; Kuo, Lih

    2016-01-01

    Purpose Hyperglycemia, a hallmark of diabetes mellitus, is associated with retinal inflammation and impairment of endothelium-dependent nitric oxide (NO)–mediated dilation of retinal arterioles. However, molecular mechanisms involved in this diminished endothelial vasodilator function remain unclear. We examined whether inflammatory stress-activated kinases, c-Jun N-terminal kinase (JNK) and p38, contribute to retinal arteriolar dysfunction during exposure to acute and chronic hyperglycemia. Methods Retinal arterioles were isolated from streptozocin-induced diabetic pigs (2 weeks; chronic hyperglycemia, 471 ± 23 mg/dL) or age-matched control pigs (euglycemia, 79 ± 5 mg/dL), and then cannulated and pressurized for vasoreactivity study. For acute hyperglycemia study, vessels from nondiabetic pigs were exposed intraluminally to high glucose (25 mM ≈ 450 mg/dL) for 2 hours, and normal glucose (5 mM ≈ 90 mg/dL) served as the control. Results Endothelium-dependent vasodilation to bradykinin was reduced in a similar manner after exposure to acute or chronic hyperglycemia. Administration of NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) nearly abolished vasodilations either in control (euglycemia and normal glucose) or hyperglycemic (acute and chronic) vessels. Treatment of either acute or chronic hyperglycemic vessels with JNK inhibitor SP600125 or JNK-interacting protein-1 (JIP1) inhibitor BI-78D3, but not p38 inhibitor SB203580, preserved bradykinin-induced dilation in an L-NAME–sensitive manner. By contrast, endothelium-independent vasodilation to sodium nitroprusside was unaffected by acute or chronic hyperglycemia. Conclusions Activation of JIP1/JNK signaling in retinal arterioles during exposure to acute or chronic hyperglycemia leads to selective impairment of endothelium-dependent NO-mediated dilation. Therapeutic targeting of the vascular JNK pathway may improve retinal endothelial vasodilator function during early diabetes. PMID

  12. Association between retinal hemorrhagic pattern and macular perfusion status in eyes with acute branch retinal vein occlusion

    PubMed Central

    Muraoka, Yuki; Uji, Akihito; Tsujikawa, Akitaka; Murakami, Tomoaki; Ooto, Sotaro; Suzuma, Kiyoshi; Takahashi, Ayako; Iida, Yuto; Miwa, Yuko; Hata, Masayuki; Yoshimura, Nagahisa

    2016-01-01

    This prospective study included 63 eyes with acute branch retinal vein occlusion (BRVO) to evaluate the retinal hemorrhagic patterns at the posterior poles and explore their clinical relevance in macular perfusion differentiation. Retinal hemorrhagic patterns and macular perfusion status were evaluated via fundus photography and fluorescein angiography, respectively. Macular perfusion was judged as nonischemic in 30, ischemic in 28, and undeterminable in 5 among the 63 eyes. Predominant hemorrhagic patterns were flame-shaped in 39 (67.2%) and non-flame-shaped in 19 (32.8%) eyes. All 39 eyes with a flame-shaped hemorrhage showed a nonischemic macula. Of the 19 eyes classified as having a non-flame-shaped hemorrhage, 13 (68.4%) had an ischemic macula and 6 (31.6%) had a nonischemic macula (P < 0.001). Parallelism in eyes with a flame-shaped hemorrhage was higher than in those with a non-flame-shaped hemorrhage (P < 0.001), and in those with a nonischemic macula versus those with an ischemic macula (P < 0.001). The area under the curve for parallelism was 0.975 (P < 0.001), suggesting an accurate diagnostic parameter for macular perfusion differentiation. In conclusion, we objectively evaluated retinal hemorrhagic patterns at the posterior pole in BRVO using the parallelism method, which was useful in differentiating macular perfusion status. PMID:27334338

  13. Involvement of All-trans-retinal in Acute Light-induced Retinopathy of Mice*S⃞

    PubMed Central

    Maeda, Akiko; Maeda, Tadao; Golczak, Marcin; Chou, Steven; Desai, Amar; Hoppel, Charles L.; Matsuyama, Shigemi; Palczewski, Krzysztof

    2009-01-01

    Exposure to bright light can cause visual dysfunction and retinal photoreceptor damage in humans and experimental animals, but the mechanism(s) remain unclear. We investigated whether the retinoid cycle (i.e. the series of biochemical reactions required for vision through continuous generation of 11-cis-retinal and clearance of all-trans-retinal, respectively) might be involved. Previously, we reported that mice lacking two enzymes responsible for clearing all-trans-retinal, namely photoreceptor-specific ABCA4 (ATP-binding cassette transporter 4) and RDH8 (retinol dehydrogenase 8), manifested retinal abnormalities exacerbated by light and associated with accumulation of diretinoid-pyridinium-ethanolamine (A2E), a condensation product of all-trans-retinal and a surrogate marker for toxic retinoids. Now we show that these mice develop an acute, light-induced retinopathy. However, cross-breeding these animals with lecithin:retinol acyltransferase knock-out mice lacking retinoids within the eye produced progeny that did not exhibit such light-induced retinopathy until gavaged with the artificial chromophore, 9-cis-retinal. No significant ocular accumulation of A2E occurred under these conditions. These results indicate that this acute light-induced retinopathy requires the presence of free all-trans-retinal and not, as generally believed, A2E or other retinoid condensation products. Evidence is presented that the mechanism of toxicity may include plasma membrane permeability and mitochondrial poisoning that lead to caspase activation and mitochondria-associated cell death. These findings further understanding of the mechanisms involved in light-induced retinal degeneration. PMID:19304658

  14. Central Retinal Artery Occlusion: A Literature Review and the Rationale for Hyperbaric Oxygen Therapy.

    PubMed

    Olson, Evan A; Lentz, Kathy

    2016-01-01

    Central retinal artery occlusion is visually devastating and has no proven treatments. The therapeutic interval between symptom onset and potentially sight-saving intervention is narrow. Traditional conservative approaches include digital massage, administration of systemic vasodilators and diuretics, and lowering of intraocular pressure. Systemic and targeted fibrinolytic therapy is under investigation but is associated with significant adverse reactions. We report a case in which hyperbaric oxygen therapy restored retinal perfusion, and the patient's vision was improved. PMID:27039492

  15. Protection of Retinal Ganglion Cells and Retinal Vasculature by Lycium Barbarum Polysaccharides in a Mouse Model of Acute Ocular Hypertension

    PubMed Central

    Mi, Xue-Song; Feng, Qian; Lo, Amy Cheuk Yin; Chang, Raymond Chuen-Chung; Lin, Bin; Chung, Sookja Kim; So, Kwok-Fai

    2012-01-01

    Acute ocular hypertension (AOH) is a condition found in acute glaucoma. The purpose of this study is to investigate the protective effect of Lycium barbarum polysaccharides (LBP) and its protective mechanisms in the AOH insult. LBP has been shown to exhibit neuroprotective effect in the chronic ocular hypertension (COH) experiments. AOH mouse model was induced in unilateral eye for one hour by introducing 90 mmHg ocular pressure. The animal was fed with LBP solution (1 mg/kg) or vehicle daily from 7 days before the AOH insult till sacrifice at either day 4 or day 7 post insult. The neuroprotective effects of LBP on retinal ganglion cells (RGCs) and blood-retinal-barrier (BRB) were evaluated. In control AOH retina, loss of RGCs, thinning of IRL thickness, increased IgG leakage, broken tight junctions, and decreased density of retinal blood vessels were observed. However, in LBP-treated AOH retina, there was less loss of RGCs with thinning of IRL thickness, IgG leakage, more continued structure of tight junctions associated with higher level of occludin protein and the recovery of the blood vessel density when compared with vehicle-treated AOH retina. Moreover, we found that LBP provides neuroprotection by down-regulating RAGE, ET-1, Aβ and AGE in the retina, as well as their related signaling pathways, which was related to inhibiting vascular damages and the neuronal degeneration in AOH insults. The present study suggests that LBP could prevent damage to RGCs from AOH-induced ischemic injury; furthermore, through its effects on blood vessel protection, LBP would also be a potential treatment for vascular-related retinopathy. PMID:23094016

  16. Case report of optic disc drusen with simultaneous peripapillary subretinal hemorrhage and central retinal vein occlusion.

    PubMed

    Law, David Zhiwei; Yang, Francine Pei Lin; Teoh, Stephen Charn Beng

    2014-01-01

    A 52-year-old Chinese gentleman presented with right eye floaters and photopsia over one week. His visual acuities were 20/20 bilaterally. Posterior segment examination showed a right eye swollen optic disc and central retinal vein occlusion (CRVO) associated with an area of subretinal hemorrhage adjacent to the optic disc. Fundus fluorescein (FA) and indocyanine green angiographies (ICGA) of the right eye did not demonstrate choroidal neovascularization (CNV), polypoidal choroidal vasculopathy (PCV), or retinal ischemia. Ultrasound B-scan revealed optic disc drusen (ODD). In view of good vision and absence of CNV, he was managed conservatively with spontaneous resolution after two months. Commonly, ODD may directly compress and mechanically rupture subretinal vessels at the optic disc, resulting in peripapillary subretinal hemorrhage, as was likely the case in our patient. Mechanical impairment of peripapillary circulation also results in retinal ischemia and may trigger the development of choroidal neovascularization (CNV) and/or polypoidal choroidal vasculopathy (PCV), leading to subretinal haemorrhage. Compromise in central venous outflow with increased retinal central venous pressure from the direct mechanical effects of enlarging ODD results in central retinal vein occlusion (CRVO). Patients with subretinal hemorrhage and CRVO from ODD should be monitored closely for the development of potentially sight-threatening complications. PMID:25544921

  17. A prospective case-control study to investigate retinal microvascular changes in acute dengue infection

    PubMed Central

    Tan, Petrina; Lye, David C.; Yeo, Tun Kuan; Cheung, Carol Y.; Thein, Tun-Linn; Wong, Joshua G.; Agrawal, Rupesh; Li, Ling-Jun; Wong, Tien-Yin; Gan, Victor C.; Leo, Yee-Sin; Teoh, Stephen C.

    2015-01-01

    Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 μm vs 144.3 μm, p < 0.001; 227.7 μm vs 212.8 μm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x104], p < 0.001; 0.849 vs 0.658 [x104], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system. PMID:26603217

  18. A prospective case-control study to investigate retinal microvascular changes in acute dengue infection.

    PubMed

    Tan, Petrina; Lye, David C; Yeo, Tun Kuan; Cheung, Carol Y; Thein, Tun-Linn; Wong, Joshua G; Agrawal, Rupesh; Li, Ling-Jun; Wong, Tien-Yin; Gan, Victor C; Leo, Yee-Sin; Teoh, Stephen C

    2015-01-01

    Dengue infection can affect the microcirculation by direct viral infection or activation of inflammation. We aimed to determine whether measured retinal vascular parameters were associated with acute dengue infection. Patients with acute dengue were recruited from Communicable Diseases Center, Singapore and age-gender-ethnicity matched healthy controls were selected from a population-based study. Retinal photographs were taken on recruitment and convalescence. A spectrum of quantitative retinal microvascular parameters (retinal vascular caliber, fractal dimension, tortuosity and branching angle) was measured using a semi-automated computer-based program. (Singapore I Vessel Assessment, version 3.0). We included 62 dengue patients and 127 controls. Dengue cases were more likely to have wider retinal arteriolar and venular calibers (158.3 μm vs 144.3 μm, p < 0.001; 227.7 μm vs 212.8 μm, p < 0.001; respectively), higher arteriolar and venular fractal dimensions (1.271 vs 1.249, p = 0.002; 1.268 vs. 1.230, p < 0.001, respectively), higher arteriolar and venular tortuosity (0.730 vs 0.546 [x10(4)], p < 0.001; 0.849 vs 0.658 [x10(4)], p < 0.001; respectively), compared to controls. Resolution of acute dengue coincided with decrease in retinal vascular calibers and venular fractal dimension. Dengue patients have altered microvascular network in the retina; these changes may reflect pathophysiological processes in the immune system. PMID:26603217

  19. Massive Retinal Pigment Epithelial Detachment Following Acute Hypokalemic Quadriparesis in Dengue Fever

    PubMed Central

    Goel, Neha; Bhambhwani, Vishaal; Jain, Pooja; Ghosh, Basudeb

    2016-01-01

    Purpose: To describe an unusual retinal manifestation of dengue fever in an endemic region. Case Report: A 35 year old male presenting with acute onset decreased vision in his right eye, was found to have a massive retinal pigment epithelial detachment (PED) extending up to the vascular arcades. He had been diagnosed with acute hypokalemic quadriparesis in dengue fever in the preceding week, which had resolved following treatment. The patient was managed conservatively. At three months follow up, there was spontaneous flattening of the PEDs with improvement in visual acuity. Conclusion: Dengue fever complicated by acute hypokalemic quadriparesis can be associated with PED, which can be large. The condition resolves spontaneously and bears a good prognosis.

  20. Unilateral sequential papillophlebitis and central retinal artery occlusion in a young healthy patient

    PubMed Central

    Demirok, Gülizar; Kocamaz, Mehmet Fatih; Topalak, Yasemin; Şengün, Ahmet; Hasanreisoğlu, Berati

    2015-01-01

    A 23-year-old girl presented to the clinic with metamorphopsia and photopsia in her left eye. After detailed ophthalmic examination, central retinal vein occlusion with optic disc edema was detected in that eye. Three days after diagnosis, the patient returned to our clinic with visual acuity decrease. Central retinal artery occlusion sparing cilioretinal artery was detected. All the laboratory tests were normal except for heterozygous methylenetetrahydrofolate reductase mutation (A1298C genotypes) and an indefinite Lyme disease seropositivity. Symptoms and visual disturbance recovered without any further treatment other than acetylsalicylic acid for prophylaxis. PMID:26862099

  1. Simulataneous occlusion of the central retinal artery and vein.

    PubMed Central

    Richards, R D

    1979-01-01

    Combined CRAO/CRVO in our patients occurred with rapid visual loss, usually over a few hours, associated with evidence of inflammation and/or cellular infiltration of the retrobulbar portion of the optic nerve. The ophthalmoscopic appearance was characteristic, with papilledema and hemorrhages of various types in the posterior pole. The retina also showed ischemic changes, with a milky-white color and cherry-red macula. Fluorescein angiography, when possible, showed no retinal vascular flow, and normal choroidal flow. After six to eight weeks, optic atrophy was evident and the retinal vessels were markedly narrowed or obliterated. The macula showed typical cystic changes. Neovascularization often developed, leading to neovascular glaucoma as the end result. Images FIGURE 1 A FIGURE 1 B FIGURE 3 A FIGURE 3 B FIGURE 2 FIGURE 4 A FIGURE 4 B FIGURE 5 FIGURE 6 FIGURE 7 A FIGURE 7 B FIGURE 7 C FIGURE 8 A FIGURE 8 B PMID:583535

  2. Significant Correlation between Retinal Venous Tortuosity and Aqueous Vascular Endothelial Growth Factor Concentration in Eyes with Central Retinal Vein Occlusion

    PubMed Central

    Yasuda, Shunsuke; Kachi, Shu; Kondo, Mineo; Ueno, Shinji; Kaneko, Hiroki; Terasaki, Hiroko

    2015-01-01

    Purpose To determine whether the degree of venous tortuosity is significantly correlated with the aqueous vascular endothelial growth factor (VEGF) concentration in eyes with a central retinal vein occlusion (CRVO). Methods We reviewed the medical records of 32 eyes of 32 patients who had macular edema due to a CRVO. All of the patients were examined at the Nagoya University Hospital and were scheduled to receive an intravitreal injection of bevacizumab (IVB) or ranibizumab (IVR) within 12 weeks of the onset of the CRVO to treat the macular edema. Aqueous humor was collected just before the IVB or IVR, and the VEGF concentration was determined by enzyme-linked immunosorbent assay (ELISA). The venous tortuosity index was calculated by dividing the length of the retinal veins by the chord length of the same segment. The correlation between the mean tortuosity index of the inferotemporal and supratemporal branches of the retinal vein and the aqueous VEGF concentration was determined. Results The mean aqueous VEGF concentration was 384 ± 312 pg/ml with a range of 90 to 1077 pg/ml. The degree of venous tortuosity was significantly correlated with the VEGF concentration in the aqueous. (r = 0.49, P = 0.004), with the foveal thickness (r = 0.40, P = 0.02), and with the best-corrected visual acuity (r = 0.38, P = 0.03). Conclusions The significant correlation between the aqueous VEGF concentration and the venous tortuosity indicates that the degree of retinal venous tortuosity can be used to identify eyes that are at a high risk of developing neovascularization. PMID:26214803

  3. Systolodiastolic variations of blood flow during central retinal vein occlusion: exploration by dynamic angiography

    PubMed Central

    Paques, M; Baillart, O; Genevois, O; Gaudric, A; Lévy, B I; Sahel, J

    2005-01-01

    Background/aim: In patients with acute central retinal vein occlusion (CRVO), dynamic angiography may reveal the presence of pulsatile flow (termed here pulsatile venular outflow, PVO) within first order veins (that is, the large veins). The main goal of this study was to investigate the mechanism underlying PVO. Methods: 10 patients with CRVO and PVO were included. Quantitative and qualitative analysis of venous flow on dynamic angiograms allowed the correlation, temporally, of second and first order vein flow on the one hand, and venous flow and systolic cycle on the other. Results: Analysis of the time-velocity curve showed that (1) the onset of arterial systole preceded the onset of PVO by less than 0.08 seconds (n = 5); (2) PVO onset was simultaneous to the time of onset of minimal flow (Vmin) in first order veins (n = 10); (3) the time of onset of maximal flow (Vmax) in first order veins occurred 0.20–0.44 seconds after the onset of PVO (n = 6). Conclusions: During CRVO with severe reduction in blood flow, the presence of PVO is the result of the existence of a distinct haemodynamic regimen in first and second order veins. These data support the hypothesis that second order veins flow is synchronous with the arterial flow, while the delayed peak flow in first order veins may reflect the consequences of the delayed IOP curve and/or of intermittent venous compression. PMID:16024861

  4. Concomitant multiple myeloma spectrum diagnosis in a central retinal vein occlusion: a case report and review.

    PubMed

    Borgman, Christopher J

    2016-07-01

    Multiple myeloma is a neoplastic plasma-cell disorder resulting from malignant plasma cells in the bone marrow. It can cause a hyperviscosity syndrome secondary to the paraproteinaemia associated with the disease. The increased hyperviscosity can lead to retinal vein occlusions and other ocular problems that may challenge clinicians. In patients with multiple myeloma and hypertension and/or diabetes mellitus, retinal changes appear similar and changes due to one disease or the other may be difficult to determine. A 48-year-old white female presented to the clinic with a complaint of blurry vision in her left eye. A full comprehensive ocular examination revealed a central retinal vein occlusion presumably from the patient's history of hypertension, diabetes mellitus and hypercholesterolaemia. Further bloodwork revealed monoclonal protein in the patient's serum and an increased percentage of plasma cells in the bone marrow. She was diagnosed with monoclonal gammopathy of undetermined significance, part of the multiple myeloma disease spectrum. She was referred to a retinal specialist for initiation of intravitreal injections of anti-vascular endothelial growth factor. Multiple myeloma has been implicated in younger patients as an underlying cause of retinal vein occlusions. Multiple myeloma should be considered as a differential diagnosis in young patients with retinal vein occlusions, even if other risk factors for venous occlusion like hypertension, diabetes mellitus and hypercholesterolaemia are present. Timely referral to the patient's primary care physician and haematologist is important for appropriate treatment and control of underlying systemic conditions. PMID:27079282

  5. Nonmydriatic retinal photography in the evaluation of acute neurologic conditions

    PubMed Central

    Bidot, Samuel; Bruce, Beau B.; Newman, Nancy J.; Biousse, Valérie

    2013-01-01

    Summary Ocular fundus examination is a fundamental component of the neurologic examination. Finding papilledema in headache patients or retinal arterial emboli in stroke patients can be extremely useful. Although examination of the ocular fundus with a direct ophthalmoscope is an important skill for all neurologists, it is rarely and unreliably performed. Nonmydriatic ocular fundus photography, which allows direct visualization of high-quality photographs of the ocular fundus, has been recently proposed for screening neurologic patients in urgent care settings such as emergency departments. This new technology has many potential applications in neurology, including e-transmission of images for remote interpretation. PMID:24353924

  6. N-acetylcysteine and acute retinal laser lesions in the colubrid snake eye

    NASA Astrophysics Data System (ADS)

    Elliott, William R., III; Rentmeister-Bryant, Heike K.; Barsalou, Norman; Beer, Jeremy; Zwick, Harry

    2004-07-01

    This study examined the role of oxidative stress and the effect of a single dose treatment with N-Acetylcysteine (NAC) on the temporal development of acute laser-induced retinal injury. We used the snake eye/Scanning Laser Ophthalmoscope (SLO) model, an in vivo, non-invasive ocular imaging technique, which has the ability to image cellular retinal detail and allows for studying morphological changes of retinal injury over time. For this study 12 corn-snakes (Elaphe g. guttata) received 5 laser exposures per eye, followed by either a single dose of the antioxidant NAC (150mg/kg, IP in sterile saline) or placebo. Laser exposures were made with a Nd: VO4 DPSS, 532nm laser, coaxially aligned to the SLO. Shuttered pulses were 20msec x 50 mW; 1mJ each. Retinal images were taken using a Rodenstock cSLO and were digitally recorded at 1, 6, 24-hrs, and at 3-wks post-exposure. Lesions were assessed by two raters blind to the conditions of the study yielding measures of damaged area and counts of missing or damaged photoreceptors. Treated eyes showed a significant beneficial effect overall, and these results suggest that oxidative stress plays a role in laser-induced retinal injury. The use of NAC or a similar antioxidant shows promise as a therapeutic tool.

  7. Activated protein C resistance in patients with central retinal vein occlusion

    PubMed Central

    Larsson, J; Sellman, A; Bauer, B

    1997-01-01

    AIM/BACKGROUND—A new defect in the anticoagulant system has recently been discovered—activated protein C resistance. The frequency of this disorder has been shown to be increased in young patients (<50 years of age) with central retinal vein occlusion. This study was carried out to determine if there was any overrepresentation of activated protein C resistance in patients >50 years of age with central retinal vein occlusion.
METHODS—Blood samples were obtained from 83 patients >50 years of age and with a history of central retinal vein occlusion. The blood samples were analysed for activated protein C resistance with standard clinical laboratory methods.
RESULTS—In this material 11% of the patients were resistant to activated protein C. The normal incidence of activated protein C resistance in the same geographical area is 10-11%.
CONCLUSION—Activated protein C resistance does not seem to be a cause of central retinal vein occlusion in people older than 50 years.

 PMID:9486021

  8. Good visual outcome in an immunocompromised patient with bilateral acute retinal necrosis syndrome: A case report

    PubMed Central

    Marrocos de Aragão, Ricardo E.; Barreira, Ieda M.A.; Arrais, Barbara L.A.; Pereira, Leidiane A.; Ramos, Carine S.

    2013-01-01

    Acute retinal necrosis (ARN) is an uncommon necrotizing, fulminant retinopathy caused by the herpes simplex virus types 1 or 2 or by the varicella zoster vírus with visually devastating consequences. Generally it occurs in patients who are systemically healthy, but occasionally occurs in immunocompromised host. We report a case of bilateral ARN in a patient with AIDS with a good final visual outcome. PMID:25278806

  9. Optic Nerve Sheath Melanoma Presenting as a Central Retinal Vein Occlusion.

    PubMed

    Barash, Alexander; Sibony, Patrick A; Stippa, Nigel A; Boyle, Nariman S; Davis, James E

    2016-03-01

    A 64-year-old woman, with a history of diabetes and melanoma, developed a central retinal vein occlusion (CRVO) in her left eye. On exam, she had severe disc edema with retinal nerve fiber layer thickening, and anterior deformation of the peripapillary retinal pigment epithelium (RPE)/Bruch membrane layer (ppRPE/BM) toward the vitreous on spectral domain optical coherence tomography (SD-OCT) suggesting an optic nerve sheath (ONS) meningioma. Magnetic resonance imaging findings and ONS biopsy later confirmed a metastatic melanoma. This case demonstrates that the shape of the RPE/BM on SD-OCT may aid in the decision to consider imaging in patients with isolated CRVO. PMID:26535468

  10. A case of presumed acute retinal necrosis after intraocular foreign body injury.

    PubMed

    Park, Sung Who; Byon, Ik Soo; Park, Hyun Jun; Lee, Ji Eun; Oum, Boo Sup

    2013-01-01

    The aim of this study was to report a case of acute retinal necrosis (ARN) after intraocular foreign body removal. A 32-year-old male presented with visual loss in the left eye. He was hit by an iron fragment while he was hammering. An intraocular foreign body was found with corneal laceration and traumatic cataract. On the day he was injured, primary closure of the laceration, lensectomy, and vitrectomy were performed, and the foreign body was removed. The day after the operation, there was no sign of retinal detachment or retinitis. Two days after the operation, retinal necrosis and accompanying vitreous inflammation were noted in the far periphery. On day 3, the necrosis spread circumferentially and inflammation became more distinct. ARN was presumed and intravenous acyclovir was administered. The necrotic areas were reduced 2 days later, and were resolved in 1 month. The final visual acuity in his left eye was 20/20 after implantation of an intraocular lens. This case is the first report of ARN after penetrating injury and an intraocular foreign body. ARN may develop after open-globe injury. PMID:23658473

  11. Acute Retinal Necrosis Associated with Epstein-Barr Virus in a Patient Undergoing Immunosuppressive Therapy

    PubMed Central

    Oe, Chiaki; Hiraoka, Miki; Tanaka, Sachie; Ohguro, Hiroshi

    2016-01-01

    Acute retinal necrosis (ARN) is a rapidly progressive and severe retinitis resulting in a poor visual outcome. Infections caused by herpes viruses such as herpes simplex virus (HSV) types 1 and 2 or the varicella zoster virus (VZV) are known to be implicated in the development of ARN. In the present study, an 80-year-old female with ARN was examined. She had been affected with rheumatoid arthritis and had taken methotrexate for over 10 years. Her right eye showed clinical features of ARN, and her left eye showed mild retinitis. The genomic DNA in the aqueous humor and vitreous fluid from her right eye were analyzed by a comprehensive polymerase chain reaction (PCR) assay to screen infectious pathogens including viruses. The Epstein-Barr virus (EBV) was detected from both specimens, but neither HSV or VZV nor cytomegalovirus was detected. She underwent intraocular surgery following systemic corticosteroid and acyclovir applications. However, although the retinitis of her right eye was extinguished, the final visual outcome was blindness due to optic nerve atrophy. There are few reports indicating that EBV is associated with ARN development. The present findings suggest that EBV alone can be the causative agent of ARN. PMID:27194989

  12. Ageing of the vitreous: From acute onset floaters and flashes to retinal detachment.

    PubMed

    Lumi, Xhevat; Hawlina, Marko; Glavač, Damjan; Facskó, Andrea; Moe, Morten C; Kaarniranta, Kai; Petrovski, Goran

    2015-05-01

    Floaters and flashes are most commonly symptoms of age-related degenerative changes in the vitreous body and posterior vitreous detachment. The etiology and pathogenesis of floaters' formation is still not well understood. Patients with acute-onset floaters, flashes and defects in their visual field, represent a medical emergency with the need for same day referral to an ophthalmologist. Indirect ophthalmoscopy with scleral indentation is needed in order to find possible retinal break(s), on-time treatment and prevention of retinal detachment. The molecular and genetic pathogenesis, as well as the epidemiology of the ageing changes of the vitreous is summarized here, with view on the several treatment modalities in relation to their success rate and side-effects. PMID:25841656

  13. Sulfur Mustard Exposure and Non-Ischemic Central Retinal Vein Occlusion.

    PubMed

    Shoeibi, Nasser; Balali-Mood, Mahdi; Abrishami, Mojtaba

    2016-01-01

    A 41-year-old man was referred with a complaint of visual loss in his left eye and his best corrected visual acuity was 20/80. Slit lamp examination showed arborizing conjunctival vessels and dry eye. Fundus examination and fluorescein angiography revealed a non-ischemic central retinal vein occlusion. Cardiovascular, rheumatologic, and hematologic work up showed no abnormal findings. An ascertained history of exposure to sulfur mustard during the Iran-Iraq war was documented in his medical history. Four sessions of intravitreal bevacizumab injections were done as needed. After two-year follow-up, visual acuity in his left eye improved to 20/25 and macular edema was resolved without any need for further interventions. We conclude that sulfur mustard gas exposure may be considered as a predisposing factor for central retinal vein occlusion, as was found in our patient (an Iranian war veteran) by excluding all yet known etiologies and predisposing factors. PMID:26722147

  14. [Personal experiences with conservative treatment of central retinal degeneration].

    PubMed

    Pojda, S M; Bandych-Biniszkiewiczowa, D

    1992-01-01

    21 patients (40 eyes) aged 27-84 years (15 women and 6 men) were treated orally with cavinton 3 x 5 mg, sadamine++ 3 X 75 mg, cinnarizine++ 3 X 40 mg, vit. A+E 3 X 1 caps. daily. Intramuscularly++ were given vit. B1 25 mg, vit. B12 1000 micrograms, geriocaine++ 100 mg, and not in all sadamine++ 300 mg daily. Improvement of visual acuity for distance was observed in 31 eyes (77.5%) and for near vision in 17 eyes (42.5%). Within 34 eyes with visual field abnormalities in 9 the central or pericentral scotomas were observed. After medical treatment the central scotomas were diminished in 6 eyes (66.6%) and the enlargement of peripheral visual border from 10 to 30 degree in 10 eyes (40%) were observed. PMID:1635363

  15. Morphologic Changes in Acute Central Serous Chorioretinopathy Using Spectral Domain Optical Coherence Tomography

    PubMed Central

    Cho, Won Bin; Chung, Hyewon

    2012-01-01

    Purpose To investigate morphologic changes of acute central serous chorioretinopathy (CSC) using spectral domain optical coherence tomography (SD-OCT) and confocal scanning laser ophthalmoscopy. Methods This retrospective study included 63 eyes of 63 patients with unilateral acute CSC. All patients underwent simultaneous SD-OCT and fluorescein angiography examination using Spectralis HRA+OCT. Results The external limiting membrane could be seen on SD-OCT, although the junction between photoreceptor inner and outer segments (IS/OS) was not detected in all eyes with retinal detachment (RD). However, IS/OS became visible after resolution of serous RD in 51 eyes (81.0%). SD-OCT images at the leakage sites showed a bump of retinal pigment epithelium (RPE) in in 47 cases (68.1%) and pigment epithelial detachment (PED) in 22 of 69 leakage sites (31.9%). In 14 of 69 leakage sites (20.3%), highly reflective areas suggesting fibrinous exudate were observed in the subretinal space. In nine leakage sites (13.0%), sagging or dipping of the posterior retinal layer was seen. Abnormal RPE changes such as RPE bump and PED were observed in 12 of 22 fellow eyes (54.5%). Conclusions A variety of morphologic changes could be identified on SD-OCT, and those findings may contribute more information to our understanding of the pathophysiology of CSC. PMID:23060721

  16. Erythropoietin administration protects retinal neurons from acute ischemia-reperfusion injury

    PubMed Central

    Junk, Anna K.; Mammis, Antonios; Savitz, Sean I.; Singh, Manjeet; Roth, Steven; Malhotra, Samit; Rosenbaum, Pearl S.; Cerami, Anthony; Brines, Michael; Rosenbaum, Daniel M.

    2002-01-01

    Erythropoietin (EPO) plays an important role in the brain's response to neuronal injury. Systemic administration of recombinant human EPO (rhEPO) protects neurons from injury after middle cerebral artery occlusion, traumatic brain injury, neuroinflammation, and excitotoxicity. Protection is in part mediated by antiapoptotic mechanisms. We conducted parallel studies of rhEPO in a model of transient global retinal ischemia induced by raising intraocular pressure, which is a clinically relevant model for retinal diseases. We observed abundant expression of EPO receptor (EPO-R) throughout the ischemic retina. Neutralization of endogenous EPO with soluble EPO-R exacerbated ischemic injury, which supports a crucial role for an endogenous EPO/EPO-R system in the survival and recovery of neurons after an ischemic insult. Systemic administration of rhEPO before or immediately after retinal ischemia not only reduced histopathological damage but also promoted functional recovery as assessed by electroretinography. Exogenous EPO also significantly diminished terminal deoxynucleotidyltransferase-mediated dUTP end labeling labeling of neurons in the ischemic retina, implying an antiapoptotic mechanism of action. These results further establish EPO as a neuroprotective agent in acute neuronal ischemic injury. PMID:12130665

  17. Bilateral Central Retinal Vein Occlusion as Presenting Feature of Chronic Myeloid Leukemia.

    PubMed

    Narang, Subina; Gupta, Panchmi; Sharma, Anuj; Sood, Sunandan; Palta, Anshu; Goyal, Shilpa

    2016-01-01

    Central retinal vein occlusion (CRVO) is a common pathology of the retinal vasculature. Patients with CRVO usually present with a drop in visual acuity. The condition bears no specific therapy; treatment is aimed at the management of potentially blinding complications, of which there are many. With majority of cases being unilateral, bilateral CRVO is usually associated with an underlying systemic illness such as a hyperviscosity syndrome. Here, we present a case of a patient, who presented with a bilateral drop in vision diagnosed as bilateral CRVO on ophthalmic evaluation. Systemic workup revealed the presence of an underlying undiagnosed chronic myeloid leukemia. An initial presentation to the ophthalmologist is a rare occurrence in leukemic patients. This case report highlights the role of the ophthalmologist in diagnosing a potentially life-threatening hematological illness. PMID:27555710

  18. Bilateral Central Retinal Vein Occlusion as Presenting Feature of Chronic Myeloid Leukemia

    PubMed Central

    Narang, Subina; Gupta, Panchmi; Sharma, Anuj; Sood, Sunandan; Palta, Anshu; Goyal, Shilpa

    2016-01-01

    Central retinal vein occlusion (CRVO) is a common pathology of the retinal vasculature. Patients with CRVO usually present with a drop in visual acuity. The condition bears no specific therapy; treatment is aimed at the management of potentially blinding complications, of which there are many. With majority of cases being unilateral, bilateral CRVO is usually associated with an underlying systemic illness such as a hyperviscosity syndrome. Here, we present a case of a patient, who presented with a bilateral drop in vision diagnosed as bilateral CRVO on ophthalmic evaluation. Systemic workup revealed the presence of an underlying undiagnosed chronic myeloid leukemia. An initial presentation to the ophthalmologist is a rare occurrence in leukemic patients. This case report highlights the role of the ophthalmologist in diagnosing a potentially life-threatening hematological illness.

  19. Anterior chamber paracentesis after central retinal artery occlusion: a tenable therapy?

    PubMed Central

    2014-01-01

    Background The goal of this study was to investigate the visual outcome of acute central retinal artery occlusion (CRAO) after current standard therapy with and without paracentesis. In addition, we investigated whether there was a dependence of the resulting visual acuity on the time between first symptoms and implementation of paracentesis. Finally, we analysed risk factors for CRAO. Methods We performed a retrospective analysis of data from patients with CRAO who received standard in-patient therapy with and without paracentesis at the Dr. Horst Schmidt Clinics in Wiesbaden, Germany between 2000 and 2012. The primary endpoint was the change of visual acuity 3 days after the initiation of intervention. Results Data from 74 patients with CRAO were included in the study. Fifteen patients were treated conservatively and 59 patients received additional paracentesis. Clinically significant improvement of BCVA (logMAR ≥ 0.3) after 3 days was observed in 26.7% of patients without paracentesis, 36.4% of patients with paracentesis within 6 hours, 20% of patients with paracentesis within 7–24 hours, and 23.1% of patients with paracentesis more than 24 hours after the onset of symptoms. There was no significant difference in the outcome between patients with (BCVA 1.9 ± 0.31) and without paracentesis (BCVA 1.75 ± 0.32) (p = 0.9), nor among the groups with paracentesis (p = 0.8). One patient suffered a lens injury due to the paracentesis, with subsequent need for cataract surgery. Conclusions There was no added gain in visual acuity by performing a paracentesis, independent of the time elapsed between first symptoms and the implementation of paracentesis. In the absence of any tangible effectiveness of paracentesis and the inherent risks of paracentesis such as intraocular infection and injury, paracentesis does not appear to be warranted as a treatment of CRAO. PMID:24612658

  20. Central Retinal Venous Pressure in Eyes of Normal-Tension Glaucoma Patients with Optic Disc Hemorrhage

    PubMed Central

    Kim, Ko Eun; Kim, Dong Myung; Flammer, Josef; Kim, Kyoung Nam

    2015-01-01

    Objective To compare central retinal venous pressure (CRVP) among eyes with and without optic disc hemorrhage (ODH) in bilateral normal-tension glaucoma (NTG) patients and NTG eyes without an episode of ODH. Methods In this prospective study, 22 bilateral NTG patients showing a unilateral ODH and 29 bilateral NTG patients without an episode of ODH were included. Eyes were categorized into group A (n = 22, eyes with ODH), group B (n = 22, fellow eyes without ODH), and group C (n = 29, NTG eyes without an episode of ODH). A contact lens ophthalmodynamometer was used to measure CRVP and central retinal arterial pressure (CRAP). Results Intraocular pressure (IOP) measured on the day of contact lens ophthalmodynamometry showed no difference among groups. However, the mean baseline IOP in group A was significantly lower than that in group C (P = .008). The CRVP in group A (29.1 ± 10.8 mmHg) was significantly lower than that in group C (40.1 ± 8.8 mmHg, P = .001), but similar to that in group B (30.5 ± 8.7 mmHg, P = .409). A similar relationship was noted for CRAP. No significant eye-associated variable for ODH was found in group A and B by conditional logistic regression analysis (all P > 0.05). However, multivariate logistic regression analysis in groups A and C revealed that low mean baseline IOP (odds ratio [OR] = 0.69, 95% confidence interval [CI] 0.49-0.98, P = 0.043) and low CRVP (OR = 0.88, 95% CI 0.80-0.95, P = 0.003) were associated with ODH. Conclusions CRVP was lower in NTG eyes with ODH than in eyes without an episode of ODH, but similar to that of fellow eyes without ODH. These imply less likelihood of association between increased central retinal venous resistance and ODH. PMID:25996599

  1. Intra-arterial thrombolysis of central retinal artery occlusion following percutaneous atrial septal defect closure.

    PubMed

    Jeon, Jin Pyeong; Cho, Young Dae; Han, Moon Hee

    2016-07-01

    Use of percutaneous devices for atrial septal defect (ASD) closure is growing, given the minimally invasive nature and the long-term durability of this approach. The reported rate of thrombus formation after catheter closure is 1.2%. Thrombotic risk varies according to closure device and Dacron-covered nitinol Amplatzer devices carry a 0-0.3% rate of thrombus formation; but central retinal artery occlusion (CRAO) is rarely implicated as an adverse event. Herein, we report the first successful intra-arterial thrombolytic treatment of CRAO developing after ASD closure via Amplatzer device. © 2015 Wiley Periodicals, Inc. PMID:26153142

  2. Importance of Central Retinal Sensitivity for Prediction of Visual Acuity after Intravitreal Bevacizumb in Eyes with Macular Edema Associated with Branch Retinal Vein Occlusion

    PubMed Central

    Sugimoto, Masahiko; Ichio, Atsushi; Kondo, Mineo

    2016-01-01

    Objective To determine whether the baseline retinal sensitivity can predict the best-corrected visual acuity (BCVA) at 1 month after intravitreal bevacizumab (IVB) in eyes with macular edema (ME) associated with a branch retinal vein occlusion (BRVO). Subjects and Methods We evaluated 16 eyes of 16 patients who had ME associated with a BRVO. The mean ± standard deviation age was 69.1 ± 8.9 years, and all had a single IVB injection. The BCVA, central macular thickness (CMT), integrity of the ellipsoid zone (EZ) of the photoreceptors, and retinal sensitivity were determined before (baseline) and at 1 day, 1 week, and 1 month following the IVB. The average threshold retinal sensitivity (AT) within the central 10° was determined by Macular Integrity Assessment. The correlations between the BCVA at 1 month and the CMT, integrity of the EZ, and AT at each visit were determined. Results One month after IVB, the BCVA improved significantly from 0.56 ± 0.27 logMAR units to 0.32 ± 0.28 logMAR units, and the CMT from 611.4 ± 209.3 μm to 258.7 ± 64.0 μm (P <0.05). The AT improved significantly from 17.9 ± 5.3 dB to 21.2 ± 5.0 dB (P <0.05). At 1 day after the treatment, both the integrity of the EZ (r = 0.59) and the retinal sensitivity (r = 0.76) were moderately correlated with the BCVA at 1 month. Conclusion These results indicate that both the integrity of the EZ and the AT at 1 day after the IVB can predict the BCVA after treatment for ME associated with BRVO. There is a possibility that these parameters will predict the effectiveness of IVB for each case. PMID:26885822

  3. Central Retinal and Posterior Ciliary Artery Occlusion After Intralesional Injection of Sclerosant to Glabellar Subcutaneous Hemangioma

    SciTech Connect

    Matsuo, Toshihiko; Fujiwara, Hiroyasu; Gobara, Hideo; Mimura, Hidefumi; Kanazawa, Susumu

    2009-03-15

    The aim of this study is to describe vision loss caused by central retinal artery and posterior ciliary artery occlusion as a consequence of sclerotherapy with a polidocanol injection to a glabellar hemangioma. An 18-year-old man underwent direct injection with a 23-gauge needle of 1 mL of a polidocanol-carbon dioxide emulsion into the glabellar subcutaneous hemangioma under ultrasound visualization of the needle tip by radiologists. He developed lid swelling the next day, and 3 days later at referral, the visual acuity in the left eye was no light perception. Funduscopy revealed central retinal artery occlusion and fluorescein angiography disclosed no perfusion at all in the left fundus, indicating concurrent posterior ciliary artery occlusion. The patient also showed mydriasis, blepharoptosis, and total external ophthalmoplegia on the left side. Magnetic resonance imaging demonstrated the swollen medial rectus muscle. In a month, blepharoptosis and ophthalmoplegia resolved but the visual acuity remained no light perception. Sclerosing therapy for facial hemangioma may develop a severe complication such as permanent visual loss.

  4. Radial optic neurotomy in treating central retinal vein occlusion: a Meta-analysis

    PubMed Central

    Chen, Zhen-Na; Shao, Yan; Li, Xiao-Rong

    2016-01-01

    AIM To assess the feasibility of radial optic neurotomy (RON) in central retinal vein occlusion (CRVO) treatment with a Meta-analysis. METHODS Electronic databases were searched for comprehensive articles that compared efficacy of RON with that of other treatments in CRVO. Study quality was assessed and risk ratio (RR) and 95% confidence interval (CI) with fix- or random-effects model were calculated according to the heterogeneity. RESULTS A total of 200 eyes from 5 studies were included. The results indicated that no significant differences were found between groups with and without RON in improvement of visual acuity (VA) at 6mo follow-up (pooled RR 0.51, 95%CI 0.22 to 1.18, P=0.117) while improvement of VA showed significantly favourable in patients receiving RON treatment at 12mo follow-up (pooled RR 2.27, 95%CI 1.31 to 3.95, P=0.004). For complications, RON treatment was more effective in reducing neovascular glaucoma (pooled RR 0.45, 95%CI 0.21 to 0.97, P=0.042) but was comparable in retinal detachment (pooled RR 2.41, 95%CI 0.51 to 11.39, P=0.267) and vitreous hemorrhage (pooled RR 0.91, 95%CI 0.33 to 2.46, P=0.847). CONCLUSION Compared with some certain treatment modalities, RON might offer better VA at 12mo and decrease the rate of neovascular glaucoma without changing the rate of retinal detachment and vitreous hemorrhage. Further studies are required considering the limitation of the research. PMID:27366695

  5. Critical appraisal of the clinical utility of the dexamethasone intravitreal implant (Ozurdex®) for the treatment of macular edema related to branch retinal vein occlusion or central retinal vein occlusion

    PubMed Central

    Chan, Annie; Leung, Loh-Shan; Blumenkranz, Mark S

    2011-01-01

    Macular edema is a common cause of visual loss in patients with retinal vein occlusions. Ozurdex®, a dexamethasone intravitreal implant, has been shown in randomized controlled trials to reduce macular edema and improve visual acuity in patients with either branch retinal vein occlusions or central retinal vein occlusions. It was approved in the United States in 2009. Since then, new therapeutic agents and clinical data have emerged. The purpose of this review is to critically evaluate the clinical utility of Ozurdex® in the current treatment strategy of macular edema related to retinal vein occlusion. PMID:21845032

  6. Central Retinal Vein Occlusion: A Review of Current Evidence-based Treatment Options

    PubMed Central

    Patel, Amy; Nguyen, Christine; Lu, Stephanie

    2016-01-01

    A central retinal vein occlusion (CRVO) can induce an ischemic and hypoxic state with resulting sequelae of macular edema and neovascularization. Many treatment options have been studied. Our review aims to investigate the safety and efficacy of the multiple treatment options of CRVO. A PubMed and Cochrane literature search was performed. Well-controlled randomized clinical trials that demonstrated strong level 1 evidence-based on the rating scale developed by the British Centre for Evidence-Based Medicine were included. Seven clinical trials met inclusion criteria to be included in this review. These included studies that investigated the safety and efficacy of retinal photocoagulation (1 study), intravitreal steroid treatment (2 studies), and antivascular endothelial growth factor treatment (4 studies) for the treatment of CRVO. In addition, studies evaluating surgical treatment options for CRVO were also included. Many treatment modalities have been demonstrated to be safe and efficacious in the treatment of CRVO. These treatment options offer therapeutic benefits for patients and clinically superior visual acuity and perhaps the quality of life after suffering from a CRVO. PMID:26957838

  7. Steroids in Central Retinal Vein Occlusion: Is There a Role in Current Treatment Practice?

    PubMed Central

    Ashraf, Mohammed; Souka, Ahmed A. R.

    2015-01-01

    With the current widespread use of anti-VEGFs in the treatment of central retinal vein occlusion (CRVO), the role for steroids has become greatly diminished. Recent large scale randomized control trials (RCTs) have established the efficacy and safety of anti-VEGFs in the treatment of CRVO. Steroids are known to cause elevations in intraocular pressure as well as increase the risk of cataract formation. With that in mind many ophthalmologists are injecting steroids less frequently. This paper aims to review some of the data pertaining to the use of steroids either as a first line monotherapy, adjunct therapy, or an alternative therapy to help answer the question: Is there currently any role for steroids in the management of CRVO? PMID:26635973

  8. Central retinal artery occlusion following orbital tumor resection: Is rapid intervention effective?

    PubMed

    Rajabi, Mohammad Taher; Naderan, Mohammad; Mohammadi, Seyed Ziaeddin Tabatabaei; Rajabi, Mohammad Bagher

    2015-08-01

    A 52-year-old male patient presented at our hospital with unilateral proptosis and vision loss in his left eye. Imaging evaluations showed orbital tumor, so the patient underwent surgery. About an hour later after tumor removal, patient developed sudden vision loss and became no light perception. Fundus evaluation revealed central retinal artery occlusion (CRAO). The patient was treated immediately with ocular massage and anterior chamber paracentesis as well as systemic therapy with mannitol and intravenous administration of acetazolamide. After thirty minutes, he recovered perception to light and then hand motion and 2 h later, it was improved to 1 m counting finger. CRAO following orbital tumor has not been reported before. We recommend ocular examination in all patients that undergo orbital surgery immediately to 2-3 h after surgery. PMID:26576528

  9. Retinal Disorders

    MedlinePlus

    ... be serious enough to cause blindness. Examples are Macular degeneration - a disease that destroys your sharp, central vision Diabetic eye disease Retinal detachment - a medical emergency, when the retina is ... children. Macular pucker - scar tissue on the macula Macular hole - ...

  10. High-dose methylprednisolone treatment of laser-induced retinal injury exacerbates acute inflammation and long-term scarring

    NASA Astrophysics Data System (ADS)

    Schuschereba, Steven T.; Cross, Michael E.; Scales, David K.; Pizarro, Jose M.; Edsall, Peter R.; Stuck, Bruce E.; Marshall, John

    1999-06-01

    Purpose. To evaluate therapeutics for attenuating retinal laser injury. Methods. New Zealand Red rabbits (n=76) were pretreated (IV) with either a single dose of hydroxyethyl starch conjugated deferoxamine (HES-DFO, n=29) (6.1 ml/kg, 16.4 mg/ml) or methylprednisolone sodium succinate (MP, n=22) (30 mg/kg, followed by taper of 30, 20, 20, and 10 mg/kg/day for a total of 5d). Controls were untreated (n=25). Fifteen min later, animals were irradiated with a multiline cw argon laser (285 mW, 10 msec pulse durations, 16 lesions/eye). Funduscopy, fluorescein angiography, histology, and morphometry were performed at 10 min, 1h, 3h, 24h, 1 mo, and 6 mo after irradiation. Leukocytes were counted at lesion centers for retinal and choroidal compartments at 1, 3, and 24h. Results. At 3h, percent area incrase for the lesions was highest for MP (44%) and lowest for HES-DFO (16%)(p<0.05). In hemorrhagic lesions, MP treatment resulted in the highest increase of retinal neotrophils by 24h (p<0.05), and by 1 and 6 mo extensive chorio-retinal scarring occurred in nonhemorrhagic and hemorrhagic lesions. Also, no benefit was demonstrated on sparing of photoreceptors with MP treatment. Conclusions. Treatment of laser-induced retinal injury with methylprednisolone (MP) exacerbates acute inflammation and long-term chorio-retinal scarring; however, hydroxyethyl starch conjugated deferoxamine therapy ameliorates these aspects of injury. Data suggest caution in the use of MP therapy for laser injuries.

  11. X-linked retinitis pigmentosa: Report of a large kindred with loss of central vision and preserved peripheral function

    SciTech Connect

    Shastry, B.S.; Trese, M.T.

    1995-11-20

    X-linked retinitis pigmentosa (XLRP) is the most severe form of the inherited forms of retinitis pigmentosa and is clinically variable and genetically heterogeneous. It affects one in 20,000 live births. The affected individuals manifest degeneration of the peripheral retina during the first two decades of life on the basis of night blindness. Central vision usually is preserved until age 50, when the disease advances, affecting central vision and ultimately leading to complete loss of sight. Linkage analysis has shown two loci with a possibility of a third locus on the human X chromosome. The genetic abnormality that causes XLRP is not known at present. Here we describe a large kindred which manifests central loss of field with the preservation of peripheral vision. 5 refs., 1 fig.

  12. Drug treatment of macular oedema secondary to central retinal vein occlusion: a network meta-analysis

    PubMed Central

    Ford, John A; Shyangdan, Deepson; Uthman, Olalekan A; Lois, Noemi; Waugh, Norman

    2014-01-01

    Objective To indirectly compare aflibercept, bevacizumab, dexamethasone, ranibizumab and triamcinolone for treatment of macular oedema secondary to central retinal vein occlusion using a network meta-analysis (NMA). Design NMA. Data sources The following databases were searched from January 2005 to March 2013: MEDLINE, MEDLINE In-process, EMBASE; CDSR, DARE, HTA, NHSEED, CENTRAL; Science Citation Index and Conference Proceedings Citation Index-Science. Eligibility criteria for selecting studies Only randomised controlled trials assessing patients with macular oedema secondary to central retinal vein occlusion were included. Studies had to report either proportions of patients gaining ≥3 lines, losing ≥3 lines, or the mean change in best corrected visual acuity. Two authors screened titles and abstracts, extracted data and undertook risk of bias assessment. Bayesian NMA was used to compare the different interventions. Results Seven studies, assessing five drugs, were judged to be sufficiently comparable for inclusion in the NMA. For the proportions of patients gaining ≥3 lines, triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of being more effective than sham and dexamethasone. A smaller proportion of patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg or aflibercept 2 mg lost ≥3 lines of vision compared to those treated with sham. Patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of improvement in the mean best corrected visual acuity compared to those treated with sham injections. Conclusions We found no evidence of differences between ranibizumab, aflibercept, bevacizumab and triamcinolone for improving vision. The antivascular endothelial growth factors (VEGFs) are likely to be favoured because they are not associated with steroid-induced cataract formation. Aflibercept may be preferred by

  13. Acute retinal necrosis in the United Kingdom: results of a prospective surveillance study

    PubMed Central

    Cochrane, T F; Silvestri, G; McDowell, C; Foot, B; McAvoy, C E

    2012-01-01

    Background To determine the incidence of acute retinal necrosis (ARN) in the United Kingdom and to describe the demographics, management, and visual outcome in these patients. Methods This was a prospective study carried out by the British Ophthalmological Surveillance Unit (BOSU) between September 2007 and October 2008. Initial and 6-month questionnaires were sent to UK ophthalmologists who reported cases of ARN via the monthly BOSU report card system. Results In all, 45 confirmed cases (52 eyes) of ARN were reported in the 14-month study period, giving a minimum incidence of 0.63 cases per million population per year. There were 20 females and 25 males. Age ranged from 10 to 94 years. Eight patients had a history of herpetic CNS disease. Aqueous sampling was carried out in 13 patients, vitreous in 27, and cerebrospinal fluid (CSF) in 4. Varicella-zoster virus followed by herpes simplex were the most common causative agents. Treatment in 76% of the cases was with intravenous antivirals; however, 24% received only oral antivirals. In all, 47% of patients had intravitreal antiviral therapy. Visual outcome at 6 months was <6/60 in 48% of the affected eyes. Conclusion The minimum incidence of ARN in the UK is 0.63 cases per million. Patients with a history of herpetic CNS disease should be warned to immediately report any visual symptoms. There is increased use of oral and intravitreal antivirals in initial treatment. PMID:22281865

  14. Anti-vascular endothelial growth factor for macular oedema secondary to central retinal vein occlusion

    PubMed Central

    Braithwaite, Tasanee; Nanji, Afshan A; Lindsley, Kristina; Greenberg, Paul B

    2014-01-01

    Background Central retinal vein occlusion (CRVO) is a relatively common retinal vascular disorder in which macular oedema may develop, with a consequent reduction in visual acuity. Until recently there has been no treatment of proven benefit, but growing evidence supports the use of anti-vascular endothelial growth factor (anti-VEGF) agents. Objectives To investigate the effectiveness and safety of anti-VEGF therapies for the treatment of macular oedema secondary to CRVO. Search methods We searched CENTRAL (which contains the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 10), Ovid MEDLINE (January 1950 to October 2013), EMBASE (January 1980 to October 2013), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to October 2013), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to October 2013), OpenGrey, OpenSIGLE (January 1950 to October 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), Clinical-Trials.gov (www.clinicaltrials.gov), the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en) and Web of Science Conference Proceedings Citation Index-Science (CPCI-S). There were no language or date restrictions in the electronic search for trials. The electronic databases and clinical trials registers were last searched on 29th October 2013. Selection criteria We considered randomised controlled trials (RCTs) that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender and a minimum of six months follow-up. Data collection and analysis Two review authors independently assessed trial quality and extracted data. The primary outcome was the proportion of participants with a gain in best-corrected visual acuity (BCVA) from baseline of

  15. The Relationship of Central Foveal Thickness to Urinary Iodine Concentration in Retinitis Pigmentosa Patients with or without Cystoid Macular Edema

    PubMed Central

    Sandberg, Michael A.; Pearce, Elizabeth N.; Harper, Shyana; Weigel-DiFranco, Carol; Hart, Lois; Rosner, Bernard; Berson, Eliot L.

    2014-01-01

    Importance Current treatments for cystoid macular edema in retinitis pigmentosa are not always effective, may lead to adverse side effects, and may not restore loss of visual acuity. The present research lays the rationale for evaluating whether an iodine supplement could reduce cystoid macular edema in retinitis pigmentosa. Objective To determine whether central foveal thickness in the presence of cystoid macular edema is related to dietary iodine intake inferred from urinary iodine concentration in non-smoking adults with retinitis pigmentosa. Design Cross-sectional study. Setting Institutional referral center. Participants Non-smoking adult patients with retinitis pigmentosa (n = 212, ages 18 to 69 years) with a visual acuity ≥ 20/200 in at least one eye. Main outcome measure The relationship of log central foveal thickness measured by optical coherence tomography to urinary iodine concentration measured from multiple spot samples and represented as a 3-level classification variable (< 100 μg/L, 100 μg/L - 199 μg/L, and ≥ 200 μg/L), assigning greater weight to patients with more reliable urinary iodine concentration estimates. Results Analyses were limited to 199 patients after excluding 11 patients who failed to return urine samples for measuring urinary iodine concentration and 2 outliers for urinary iodine concentration. Thirty-six percent of these patients had cystoid macular edema in one or both eyes. Although log central foveal thickness was inversely related to urinary iodine concentration based on all patients (p = 0.02), regression of log central foveal thickness on urinary iodine concentration separately for patients with and without cystoid macular edema showed a strong inverse significant relationship for the former group (p < 0.001) and no significant relationship for the latter group as tested (p = 0.66). In contrast, we found no significant association between cystoid macular edema prevalence and urinary iodine concentration based on the

  16. Assessment of visual function and retinal structure following acute light exposure in the light sensitive T4R rhodopsin mutant dog.

    PubMed

    Iwabe, Simone; Ying, Gui-Shuang; Aguirre, Gustavo D; Beltran, William A

    2016-05-01

    weeks post LE with more severe damage at 36 weeks post LE in all four meridians. The RHO(T4R/T4R) retina exposed to the high dose showed at 2 weeks after LE extensive ONL damage in all four meridians. This light intensity did not cause any retinal damage in WT dogs even after repeated (up to 3) LE. Analysis of ONL thickness in heterozygous mutant dogs exposed to the moderate dose of light confirmed the increased sensitivity to light damage of the superior/tapetal retina, and the occurrence of an ongoing cell death process several weeks after the acute LE. In conclusion, a short single exposure to a dose of white light that is not retinotoxic in WT dogs causes in the T4R RHO retina an acute loss of ONL in the central to mid peripheral region that keeps progressing over the course of several weeks. However, this severe retinal damage does not affect visual behavior presumably because of islands of surviving photoreceptors found in the area centralis including the newly discovered canine fovea-like area, and the lack of damage to peripheral photoreceptors. PMID:27085210

  17. ASSESSMENT OF VISUAL FUNCTION AND RETINAL STRUCTURE FOLLOWING ACUTE LIGHT EXPOSURE IN THE LIGHT SENSITIVE T4R RHODOPSIN MUTANT DOG

    PubMed Central

    Iwabe, Simone; Ying, Gui-Shuang; Aguirre, Gustavo D.; Beltran, William A.

    2016-01-01

    severe damage at 36 weeks post LE in all four meridians. The RHOT4R/T4R retina exposed to the high dose showed at 2 weeks after LE extensive ONL damage in all four meridians. This light intensity did not cause any retinal damage in WT dogs even after repeated (up to 3) LE. Analysis of ONL thickness in heterozygous mutant dogs exposed to the moderate dose of light confirmed the increased sensitivity to light damage of the superior/tapetal retina, and the occurrence of an ongoing cell death process several weeks after the acute LE. In conclusion, a short single exposure to a dose of white light that is not retinotoxic in WT dogs causes in the T4R RHO retina an acute loss of ONL in the central to mid peripheral region that keeps progressing over the course of several weeks. However, this severe retinal damage does not affect visual behavior presumably because of islands of surviving photoreceptors found in the area centralis including the newly discovered canine fovea-like area, and the lack of damage to peripheral photoreceptors. PMID:27085210

  18. A 25-Year-Old Man with Exudative Retinal Detachments and Infiltrates without Hematological or Neurological Findings Found to Have Relapsed Precursor T-Cell Acute Lymphoblastic Leukemia

    PubMed Central

    Johnson, Jordan S.; Lopez, James S.; Kavanaugh, Arthur Scott; Liang, Chanping; Mata, Douglas A.

    2015-01-01

    Background Precursor T-cell acute lymphoblastic leukemia (pre-T-ALL) may cause ocular pathologies such as cotton-wool spots, retinal hemorrhage, and less commonly, retinal detachment or leukemic infiltration of the retina itself. However, these findings are typically accompanied by the pathognomonic hematological signs of acute leukemia. Case Presentation In this case report and review of the literature, we describe a particularly unusual case of a 25-year-old man who presented to our hospital with bilateral exudative retinal detachments associated with posterior pole thickening without any hematological or neurological findings. The patient, who had a history of previously treated pre-T-ALL in complete remission, was found to have leukemia cell infiltration on retinal biopsy. Conclusion Our case underscores the fact that the ophthalmologist may be the first provider to detect the relapse of previously treated leukemia, and that ophthalmic evaluation is critical for detecting malignant ocular infiltrates. PMID:26483676

  19. Central retinal artery occlusion following laser treatment for ocular ischemic aortic arch syndrome

    PubMed Central

    Shah, Payal J.; Ellis, Brian; DiGiovine, Lauren R.; Hogg, Jeffery P.; Leys, Monique J.

    2015-01-01

    Objective: Ocular ischemic syndrome is a rare blinding condition generally caused by disease of the carotid artery. We describe a 69-year-old female with a 50 pack-year smoking history with aortic arch syndrome causing bilateral ocular ischemic syndrome. Methods: The patient presented with progressive visual loss and temple pain. Slit lamp biomicroscopy revealed bilateral iris neovascularization. This finding prompted a cardiovascular work up. Panretinal photocoagulation with retrobulbar block was performed in the right eye. Results: A temporal artery biopsy was negative. The carotid duplex ultrasound showed only a 1–39% stenosis. MRA revealed a more proximal occlusion of the aortic branch for which she underwent subclavian carotid bypass surgery. At the one month follow up, the right eye suffered profound vision loss secondary to a central retinal artery occlusion. Conclusion: Ocular neovascularization may be one of the clinical manifestations of aortic arch syndrome. This case also illustrates the limitations of relying solely on carotid duplex ultrasound testing. We caution against overly aggressive panretinal photocoagulation utilizing retrobulbar anesthesia.

  20. Vision Loss by Central Retinal Vein Occlusion After Kaatsu Training: A Case Report.

    PubMed

    Ozawa, Yoko; Koto, Takashi; Shinoda, Hajime; Tsubota, Kazuo

    2015-09-01

    Kaatsu training is an exercise method involving the application of pressure to the target muscle, and is being increasingly used in rehabilitation programs for heart disease patients in some hospitals. This method restricts blood flow to the muscles during exercise, and the resultant hypoxia effectively causes muscle hypertrophy and strengthening. However, no medical guidelines or risk factors for its use have been established.We report a case involving a 45-year-old man who suffered from 2 episodes of central retinal vein occlusion (CRVO), both occurring on the day following a Kaatsu training session.As a characteristic of the CRVO and its subsequent complications, the affected eye lost vision despite treatment. The patient had a history of hypertension and diabetes, and thus was at an increased risk of CRVO. Kaatsu training, which changes the heart rate and serum growth hormone levels, may have triggered the onset of CRVO.This case highlights that underlying medical conditions such as hypertension, diabetes, and the consequent inflammation, could be risk factors for vascular side effects resulting from Kaatsu training. Further studies are required before the medical and recreational use of Kaatsu training become widespread. PMID:26356723

  1. The association of central retinal artery occlusion and extracranial carotid artery disease.

    PubMed Central

    Douglas, D J; Schuler, J J; Buchbinder, D; Dillon, B C; Flanigan, D P

    1988-01-01

    To determine the incidence of associated carotid artery disease and the effect of carotid endarterectomy on subsequent neurologic sequelae, a retrospective study of 66 patients with central retinal artery occlusion (CRAO) was undertaken. Ipsilateral extracranial carotid artery disease was present in 23 of 33 patients (70%) who had carotid arteriography. Sixteen patients had carotid endarterectomy following their CRAO (Group I) and 50 did not (Group II). Seven of the 40 patients available for follow-up in Group II had a subsequent stroke (mean follow-up: 54 months). Of the seven Group II patients shown to have associated carotid disease (Group IIs), three (43%) had a subsequent stroke during follow-up (mean: 28.3 months) compared to zero in Group I (p = 0.033; mean follow-up: 18.7 months). Because of the strong association between CRAO and ipsilateral carotid artery disease and because of the significantly higher incidence of subsequent ipsilateral stroke in CRAO patients with carotid disease who did not undergo endarterectomy, thorough evaluation of the carotid arteries followed by carotid endarterectomy, if indicated, is warranted in CRAO patients who have no other obvious etiology for the occlusion. PMID:3389947

  2. Early panretinal photocoagulation for the treatment of ischemic central retinal vein occlusion

    NASA Astrophysics Data System (ADS)

    Yu, Zikui; He, Naizhen

    2005-07-01

    Objective: To evaluate the safety and efficacy of treating ischemic central retinal vein occlusion (CRVO)with early panretinal photocoagulation(PRP). Methods:24 eyes of 24 cases suffered from ischemic CRVO with history shorter than 3 months were included in this study. PRP treatments were completed through 3 to 5 times of laser therapy with total laser burns of 1000 to 2000(mean 1505+/-384).Patients were followed up 3 months to 2 years, mean 18.4+/-8.0 months.The neovascularization regression and visual acuity were compared before and after PRP, also the long-term complications were observed. Results:3 eyes of iris neovascularization (INV) regressed after PRP and there was no significant difference in visual acuity between prelaser and postlaser. No neovascular glaucoma(NVG) occurred and 2 eyes occurred vitreous hemorrhage during the follow up period.. Conclusions: Early panretinal photocoagulation is safe and efficacious in preventing and reducing complications of ischemic CRVO. It can save valuable treatment time for some patients

  3. Hyperbaric oxygen for the treatment of the rare combination of central retinal vein occlusion and cilioretinal artery occlusion.

    PubMed

    Celebi, Ali Riza Cenk; Kilavuzoglu, Ayse Ebru; Altiparmak, Ugur Emrah; Cosar, C Banu; Ozkiris, Abdullah

    2016-03-01

    A 43-year-old male presented with sudden onset of painless, blurred vision in his left eye. Dilated fundoscopic examination showed signs consistent with the diagnosis of a combination of central retinal vein occlusion (CRVO) and cilioretinal artery occlusion (CLRAO). He received daily 2-h sessions of hyperbaric oxygen treatment (HBOT), 253 kPa for 14 days. At the end of the HBOT course, the patient's left visual acuity had improved from 20/200 to 20/20. Dilated fundoscopic examination showed that the intra-retinal haemorrhages in the entire retina and the retinal whitening along the course of the CLRA seen at presentation had completely resolved. The combination of CLRAO and CRVO comprises a discrete clinical entity. Even though there are many hypotheses concerning this condition, it is most likely the result of elevated intraluminal pressure in the retinal capillaries due to CRVO that exceeds the pressure in the CLRA. HBOT may be an effective treatment for CRVO-associated CLRAO. PMID:27044464

  4. The discrepancy between central foveal thickness and best corrected visual acuity in cystoid macular edema secondary to central retinal vein occlusion after intravitreal lucentis® injection.

    PubMed

    Hua, Rui; Li, Chenyan; Hu, Yuedong; Chen, Lei

    2015-06-01

    Cystoid macular edema is a common retinal disorder with the potential for significant vision-related morbidity, and intravitreal lucentis(®) injection is confirmed to be an effective therapy approach. In the present study, we investigated the discrepancy between central foveal thickness and best corrected visual acuity in such lesions and infered that intravitreal lucentis(®) injection may help the visual function, related to the renewal of cells. PMID:25818575

  5. Anti-vascular endothelial growth factor for macular edema secondary to central retinal vein occlusion

    PubMed Central

    Braithwaite, Tasanee; Nanji, Afshan A; Greenberg, Paul B

    2014-01-01

    Background Central retinal vein occlusion (CRVO) is a common retinal vascular disorder in which macular edema (ME) may develop, with a consequent reduction in visual acuity. The visual prognosis in CRVO-ME is poor in a substantial proportion of patients, especially those with the ischemic subtype, and until recently there has been no treatment of proven benefit. Macular grid laser treatment is ineffective, and whilst a few recent randomized controlled trials (RCTs) suggest short-term gains in visual acuity with intravitreal steroids for patients with non-ischemic CRVO-ME, there is no established treatment for ischemic CRVO-ME. Anti-vascular endothelial growth factor (anti-VEGF) agents have been used to treat ME resulting from a variety of causes and may represent a treatment option for CRVO-ME. Objectives To investigate the effectiveness and safety of intravitreal anti-VEGF agents in the treatment of CRVO-ME. Search strategy We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2010, Issue 8), MEDLINE (January 1950 to August 2010), EMBASE (January 1980 to August 2010), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to August 2010), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to August 2010), OpenSIGLE (January 1950 to August 2010), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and ClinicalTrials.gov (www.clinicaltrials.gov). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 10 August 2010. Selection criteria We considered RCTs that compared intravitreal anti-VEGF agents of any dose or duration to sham injection or no treatment. We focused on studies that included individuals of any age or gender with unilateral or bilateral disease and a minimum of six months follow up. Secondarily, we

  6. Central Retinal Enrichment Supplementation Trials (CREST): Design and Methodology of the CREST Randomized Controlled Trials

    PubMed Central

    Beatty, Stephen; Stack, Jim; Dennison, Jessica; O’Regan, Sarah; Meagher, Katherine A.; Peto, Tunde; Nolan, John

    2014-01-01

    Purpose The Central Retinal Enrichment Supplementation Trials (CREST) aim to investigate the potential impact of macular pigment (MP) enrichment, following supplementation with a formulation containing 10 mg lutein (L), 2 mg zeaxanthin (Z) and 10 mg meso-zeaxanthin (MZ), on visual function in normal subjects (Trial 1) and in subjects with early age-related macular degeneration (AMD; Trial 2). Methods CREST is a single center, double-blind, randomized clinical trial. Trial 1 (12-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ and 2 mg Z (n = 60) or placebo (n = 60). Trial 2 (24-month follow-up) subjects are randomly assigned to a formulation containing 10 mg L, 10 mg MZ, 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention A; n = 75) or 10 mg L and 2 mg Z plus 500 mg vitamin C, 400 IU vitamin E, 25 mg zinc and 2 mg copper (Intervention B; n = 75). Contrast sensitivity (CS) at 6 cycles per degree represents the primary outcome measure in each trial. Secondary outcomes include: CS at other spatial frequencies, MP, best-corrected visual acuity, glare disability, photostress recovery, light scatter, cognitive function, foveal architecture, serum carotenoid concentrations, and subjective visual function. For Trial 2, AMD morphology, reading speed and reading acuity are also being recorded. Conclusions CREST is the first study to investigate the impact of supplementation with all three macular carotenoids in the context of a large, double-blind, randomized clinical trial. PMID:24621122

  7. Branch retinal vein occlusion.

    PubMed

    Hamid, Sadaf; Mirza, Sajid Ali; Shokh, Ishrat

    2008-01-01

    Retinal vein occlusions (RVO) are the second commonest sight threatening vascular disorder. Branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO) are the two basic types of vein occlusion. Branch retinal vein occlusion is three times more common than central retinal vein occlusion and- second only to diabetic retinopathy as the most common retinal vascular cause of visual loss. The origin of branch retinal vein occlusion undoubtedly includes both systemic factors such as hypertension and local anatomic factors such as arteriovenous crossings. Branch retinal vein occlusion causes a painless decrease in vision, resulting in misty or distorted vision. Current treatment options don't address the underlying aetiology of branch retinal vein occlusion. Instead they focus on treating sequelae of the occluded venous branch, such as macular oedema, vitreous haemorrhage and traction retinal detachment from neovascularization. Evidences suggest that the pathogenesis of various types of retinal vein occlusion, like many other ocular vascular occlusive disorders, is a multifactorial process and there is no single magic bullet that causes retinal vein occlusion. A comprehensive management of patients with retinal vascular occlusions is necessary to correct associated diseases or predisposing abnormalities that could lead to local recurrences or systemic event. Along with a review of the literature, a practical approach for the management of retinal vascular occlusions is required, which requires collaboration between the ophthalmologist and other physicians: general practitioner, cardiologist, internist etc. as appropriate according to each case. PMID:19385476

  8. Clinical and multimodal imaging characteristics of acute Vogt-Koyanagi-Harada disease unassociated with clinically evident exudative retinal detachment.

    PubMed

    Attia, Sonia; Khochtali, Sana; Kahloun, Rim; Ammous, Dhiaeddine; Jelliti, Bechir; Ben Yahia, Salim; Zaouali, Sonia; Khairallah, Moncef

    2016-02-01

    The purpose of this study was to describe the clinical and multimodal imaging findings in acute Vogt-Koyanagi-Harada (VKH) disease without clinically evident exudative retinal detachment (ERD). We retrospectively reviewed the charts of 18 patients (36 eyes), diagnosed with acute VKH disease without clinically evident ERD. All patients underwent complete ophthalmic examination, fundus photography, optical coherence tomography (OCT), B-scan ultrasonography, fluorescein angiography (FA), and indocyanine green angiography (ICGA). Of 18 patients, twelve (66.7 %) were female and 6 (33.3 %) were male. Mean age was 39 years (range, 23-60). Ten patients had been referred with an erroneous diagnosis of primary optic nerve disorder (8; 44.4 %) or isolated anterior uveitis (2; 11.1 %). Anterior chamber or vitreous inflammatory reaction was noted in 22 eyes (61.1 %), each. Fundus findings included optic disc swelling in 30 eyes (83.3 %), retinal striae in 20 eyes (55.5 %), and yellowish deep lesions in 3 eyes (8.3 %). OCT showed a shallow, localized subclinical ERD in 18 eyes (50 %), and retinal pigment epithelial folds in 23 eyes (63.9 %). B-scan ultrasonography showed diffuse, low- to medium-reflective choroidal thickening in all eyes. FA disclosed delayed choroidal perfusion in at least one eye of all patients (100 %), mild pinpoint leakage in 21 eyes (58.3 %), optic disc hyperfluorescence in 35 eyes (97.2 %) and choroidal folds in 13 eyes (36.1 %). ICGA findings included delayed choroidal perfusion in 24 eyes (66.7 %), decrease in the number of large choroidal vessels in 36 eyes (100 %), fuzzy choroidal vessels in 35 eyes (97.2 %), and hypofluorescent dark dots in 28 eyes (77.8 %). The association of bilateral optic disc edema with retinal striae and intraocular inflammatory reaction highly suggests acute VKH disease. A multimodal imaging approach including fundus photography, OCT, B-scan ultrasonography, FA, and ICGA provides important clues for the definite diagnosis and

  9. Retinal imaging with adaptive optics scanning laser ophthalmoscopy in unexplained central ring scotoma.

    PubMed

    Joeres, Sandra; Jones, Steven M; Chen, Diana C; Silva, Dennis; Olivier, Scot; Fawzi, Amani; Castellarin, Alessandro; Sadda, Srinivas R

    2008-04-01

    Adaptive optics scanning laser ophthalmoscopy allows for noninvasive, in vivo visualization of retinal abnormalities at a cellular level. We herein describe for the first time, to our knowledge, the utility of high-resolution retinal imaging in studying the photoreceptor mosaic in an otherwise unexplained visual disturbance. Imaging of the cone mosaic was performed in a 64-year-old man with a unilateral ringlike paracentral distortion that could not be explained using common clinical imaging instruments. Adaptive optics scanning laser ophthalmoscopy findings revealed a parafoveal circular abnormality of the cone mosaic approximately 3 degrees in diameter that corresponded to the ring of visual disturbance. Visualization of the cone mosaic with adaptive optics scanning laser ophthalmoscopy can reveal photoreceptor damage that may not be detectable with standard imaging devices. Optical axial sectioning of the retina may help in identifying and localizing abnormalities within the retinal layers. PMID:18413527

  10. Retinitis Pigmentosa

    MedlinePlus

    ... Action You are here Home › Retinal Diseases Listen Retinitis Pigmentosa What is retinitis pigmentosa? What are the symptoms? ... available? Are there any related diseases? What is retinitis pigmentosa? Retinitis pigmentosa (RP) refers to a group of ...

  11. Combined Central Retinal Artery and Vein Occlusion Associated with Factor V Leiden Mutation and Treated with Hyperbaric Oxygen

    PubMed Central

    Lemos, José Alberto; Teixeira, Carla; Carvalho, Rui; Fernandes, Tiago

    2015-01-01

    Background Combined central retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO) is an uncommon retinal vascular disease which causes sudden visual acuity loss and is associated with poor prognosis and the development of severe complications. We report a very rare case of combined CRAO and CRVO in a patient with factor V Leiden (FVL) mutation (only 3 cases published). To our knowledge, this is the first case of combined CRAO and CRVO treated with hyperbaric oxygen therapy (HBOT). Case and Results A 49-year-old woman presented with complaints of sudden loss of vision in her left eye (LE), with best corrected visual acuity (BCVA) of 1/20. A complete ophthalmic evaluation with fundus angiography showed combined CRAO and CRVO. The patient was urgently treated with HBOT (she completed a total of 9 sessions in 7 days), with marked visual acuity and angiographic improvement (BCVA of 10/10). Forty-five days later, she developed a new LE CRVO, and BCVA decreased to 5/10 and later to <1/20 because of significant macular edema. A detailed investigation showed an abnormal resistance to activated protein C, and a genetic study showed homozygosity for FVL mutation. The patient was submitted to 3 monthly injections of 1.25 mg bevacizumab. After 10 months, the patient is in a stable condition with BCVA of 6/10. Conclusions Combined CRAO and CRVO in young adults should be investigated thoroughly for embolic sources, thrombophilic disorders and local ocular conditions. This is the first case of this severe disease that was treated with HBOT, and the visual result was very good. PMID:26955350

  12. Manifestations of central retinal artery occlusion revealed by fundus fluorescein angiography are associated with the degree of visual loss

    PubMed Central

    GONG, HONGXIA; SONG, QIUYING; WANG, LANHUI

    2016-01-01

    The aim of this study was to investigate the association between central visual impairment and the characteristics of fundus fluorescein angiography (FFA) in patients with central retinal artery occlusion (CRAO). A total of 63 patients were diagnosed with CRAO by FFA. The visual dysfunction was classified into severe, mild and light degrees. Tropicamide was administered for mydriasis. FFA examination was performed using Heidelberg retinal tomography. The associations of age, gender and disease course with CRAO type were analyzed. Three types of manifestations were identified by FFA in 63 eyes, including poor perfusion (18 cases), exudation (22 cases) and mixed types (23 cases) of CRAO. No significant difference was found in age (F=0.171, P=0.844) and disease course (F=0.016, P=0.984) among the three types of CRAO. Similarly, no significant difference was found in gender among the three types of CRAO (χ2=0.176, P=0.916). The damage to vision caused by the exudation type of CRAO was not as severe as that caused by the poor perfusion and mixed types of CRAO. The distributions of damage severity caused by the poor perfusion and mixed types of CRAO were similar. In conclusion, the FFA observations for CRAO can be classified into three types of manifestations. The damage to vision in patients with CRAO is likely to be associated with poor perfusion in the retinal artery rather than exudation affecting the retina or optic disc. The patterns of clinical manifestations are not associated with age, gender or disease course. PMID:27313672

  13. Increased Risk of Acute Angle Closure in Retinitis Pigmentosa: A Population-Based Case-Control Study

    PubMed Central

    Ko, Yu-Chieh; Liu, Chia-Jen; Hwang, De-Kuang; Chen, Tzeng-Ji; Liu, Catherine J.

    2014-01-01

    Purpose To investigate the association between retinitis pigmentosa (RP) and acute angle closure during a 15-year follow-up period. Methods Using the Taiwan Longitudinal Health Insurance Database 2000, we identified 382 RP patients based on the diagnostic code of RP (International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) 362.74) made during 1996–2010, excluding subjects under age of 20 years at diagnosis or subjects undergoing lens extraction before the index date. The control group included 3820 randomly selected non-RP subjects matched with the RP patients in age, gender and the index date of diagnosis. The incidence of acute angle closure during the study period was observed based on an ICD-9-CM code of 365.22. Cochran-Mantel-Haenszel test was used to determine the odds ratio (OR) of having acute angle closure in RP patients. Results The mean age at the diagnosis of RP was 51.1years (standard deviation [SD] 16.7). Acute angle closure occurred in 5 RP patients (1.3%) and in 15 controls (0.4%). The mean age with the acute angle closure was 53.3 years (SD 8.0) in RP patients and 64.6 years (SD 8.4) in controls (P = 0.015). After adjusting for age, gender and comorbid disorders, RP patients had 3.64-fold (95% confidence interval [CI], 1.29–10.25, P<0.001) greater odds of having acute angle closure. After stratification for gender and age, the risk of acute angle closure in RP was higher in patients under age of 60 years (adjusted OR 11.84; 95% CI, 2.84–49.48) and male patients (adjusted OR 19.36; 95% CI, 3.43–109.40)(both P = 0.001). Conclusions RP patients had increased risk of acute angle closure than controls. Contrary to the fact that angle closure disease is more prevalent in elderly females in general population, acute angle closure attack occurred earlier in life and the risk was higher in males among RP patients. PMID:25222486

  14. Delayed diagnosis of ocular syphilis that manifested as retinal vasculitis and acute posterior multifocal placoid epitheliopathy.

    PubMed

    Park, Jong Hoon; Joe, Soo Geun; Yoon, Young Hee

    2013-11-01

    A 55-year-old female presented with bilateral progressive retinal vasculitis. She was on systemic and intravitreal steroids on the basis of uveitis work-up result (negative result including rapid plasma reagin), but her visual acuity continued to deteriorate to light perception only. Ocular examination showed retinal vasculitis, multiple yellow placoid lesions and severe macula edema in both eyes. Repeated work-up revealed positivity of fluorescent treponemal antibody-absorption in serum and subsequently in cerebrospinal fluid. Ocular syphilis was diagnosed. And intravenous penicillin G resulted in rapid resolution of vasculitis and macular edema. To avoid delay in the diagnosis of ocular syphilis, high index of suspicion and repeating serological tests (including both treponemal and non-treponemal tests) are warranted. PMID:24145569

  15. Gravity sensing in the retinal spreading depression, an in-vitro model for the central nervous system (CNS)

    NASA Astrophysics Data System (ADS)

    Wiedemann, Meike; Piffel, Alexandra; Hanke, Wolfgang

    2005-08-01

    The retinal spreading depression (SD) was used to study the effects of altered gravity on the central nervous system (CNS). The SD is an excitation depression wave and an example of self-organization and pattern formation in neuronal tissue being an excitable media. Until now it is not much known about how changes in gravity effect the central nervous system. Here we present the results of SD experiments on a sounding rocket mission (TEXUS 41) and the comparison to earlier SD experiments on parabolic flights (2nd and 3rd DLR Parabolic flight campaign) and centrifuge experiments in our lab. The results of these experimetns show that the properties of the SD and therefore the CNS in its properties as an excitable medium reacts very sensitive to changes in gravity.

  16. Anterior Lamina Cribrosa Surface Depth in Open-Angle Glaucoma: Relationship with the Position of the Central Retinal Vessel Trunk

    PubMed Central

    Oh, Baek-Lok; Kim, Hyunjoong; Girard, Michaël J. A.; Mari, Jean Martial; Kim, Tae-Woo

    2016-01-01

    Purpose To determine the factors influencing the anterior lamina cribrosa (LC) surface depth (LCD) in patients with open-angle glaucoma (OAG), focusing on the association between LCD and the position of the central retinal vessel trunk (CRVT) at the anterior LC surface. Methods Optic nerve heads of 205 OAG eyes were scanned using swept-source optical coherence tomography (SS-OCT). After processing the images using adaptive compensation, the LCD was determined from 11 horizontal B-scan images that divided the optic disc vertically into 12 equal parts. Eyes were divided into two groups (central or peripheral) according to where the CRVT exits from the anterior LC surface. The influence of CRVT position on LCD was evaluated, taking into account age, gender, untreated intraocular pressure (IOP), IOP at optic-disc scanning, retinal nerve fiber layer (RNFL) thickness, visual-field mean deviation, central corneal thickness, and axial length. Results Patients in the peripheral CRVT group were younger and more myopic, and had a larger mean LCD and thinner global RNFL than those in the central CRVT group (all P≤0.023). On multivariate analysis, the peripheral CRVT location was significantly associated with a larger LCD (P = 0.002), together with the significant association of younger age (P<0.001), higher untreated IOP (P = 0.010), and thinner RNFL (P = 0.003) on the larger LCD. Conclusion In OAG, CRVT location was an independent factor influencing the LCD, together with age, untreated IOP, and global RNFL thickness. The data indicate that the CRVT may contribute to the resistance of the LC against deformation. A longitudinal prospective observation is required to clarify this relationship. PMID:27355646

  17. Central nervous system effects in acute thallium poisoning.

    PubMed

    Tsai, Yu-Tai; Huang, Chin-Chang; Kuo, Hung-Chou; Wang, Hsuan-Min; Shen, Wu-Shiun; Shih, Tung-Sheng; Chu, Nai-Shin

    2006-03-01

    We report the central nervous system manifestations, neuropsychological studies and brain magnetic resonance image (MRI) findings of two patients with acute thallium intoxication. Neurologically the patients suffered from confusion, disorientation, and hallucination in the acute stage, followed by anxiety, depression, lack of attention, and memory impairment, in addition to peripheral neuropathy. Neuropsychological tests revealed an impairment of memory function, including reversed digital span, memory registration, memory recall, memory recognition, similarity, proverb reasoning, and verbal fluency. High concentrations of thallium were found in the urine, blood, and drinking water of these two patients. Brain MRI showed lesions in the corpus striatum in one patient. During the follow-up periods, the clinical manifestations and neuropsychological studies showed a slowly progressive improvement, and a follow-up brain MRI 1.5 months later demonstrated a resolution of the lesions. We conclude that thallium intoxication might induce encephalopathy, and brain MRI studies demonstrated the acute-stage brain lesions in a severe intoxicated patient. In addition, neuropsychological tests also confirmed memory deficits, although the brain lesions in the corpus striatum might resolve. PMID:16337004

  18. The Relationship between OCT-measured Central Retinal Thickness and Visual Acuity in Diabetic Macular Edema

    PubMed Central

    2008-01-01

    Objective To compare optical coherence tomography (OCT)-measured retinal thickness and visual acuity in eyes with diabetic macular edema (DME) both before and after macular laser photocoagulation. Design Cross-sectional and longitudinal study. Participants 210 subjects (251 eyes) with DME enrolled in a randomized clinical trial of laser techniques. Methods Retinal thickness was measured with OCT and visual acuity was measured with the electronic-ETDRS procedure. Main Outcome Measures OCT-measured center point thickness and visual acuity Results The correlation coefficients for visual acuity versus OCT center point thickness were 0.52 at baseline and 0.49, 0.36, and 0.38 at 3.5, 8, and 12 months post-laser photocoagulation. The slope of the best fit line to the baseline data was approximately 4.4 letters (95% C.I.: 3.5, 5.3) better visual acuity for every 100 microns decrease in center point thickness at baseline with no important difference at follow-up visits. Approximately one-third of the variation in visual acuity could be predicted by a linear regression model that incorporated OCT center point thickness, age, hemoglobin A1C, and severity of fluorescein leakage in the center and inner subfields. The correlation between change in visual acuity and change in OCT center point thickening 3.5 months after laser treatment was 0.44 with no important difference at the other follow-up times. A subset of eyes showed paradoxical improvements in visual acuity with increased center point thickening (7–17% at the three time points) or paradoxical worsening of visual acuity with a decrease in center point thickening (18%–26% at the three time points). Conclusions There is modest correlation between OCT-measured center point thickness and visual acuity, and modest correlation of changes in retinal thickening and visual acuity following focal laser treatment for DME. However, a wide range of visual acuity may be observed for a given degree of retinal edema and paradoxical

  19. Central adiponectin acutely improves glucose tolerance in male mice.

    PubMed

    Koch, Christiane E; Lowe, Chrishanthi; Legler, Karen; Benzler, Jonas; Boucsein, Alisa; Böttiger, Gregor; Grattan, David R; Williams, Lynda M; Tups, Alexander

    2014-05-01

    Adiponectin, an adipocyte-derived hormone, regulates glucose and lipid metabolism. It is also antiinflammatory. During obesity, adiponectin levels and sensitivity are reduced. Whereas the action of adiponectin in the periphery is well established the neuroendocrine role of adiponectin is largely unknown. To address this we analyzed the expression of adiponectin and the 2 adiponectin receptors (AdipoR1 and AdipoR2) in response to fasting and to diet-induced and genetic obesity. We also investigated the acute impact of adiponectin on central regulation of glucose homeostasis. Adiponectin (1 μg) was injected intracerebroventricularly (ICV), and glucose tolerance tests were performed in dietary and genetic obese mice. Finally, the influence of ICV adiponectin administration on central signaling cascades regulating glucose homeostasis and on markers of hypothalamic inflammation was assessed. Gene expression of adiponectin was down-regulated whereas AdipoR1 was up-regulated in the arcuate nucleus of fasted mice. High-fat (HF) feeding increased AdipoR1 and AdipoR2 gene expression in this region. In mice on a HF diet and in leptin-deficient mice acute ICV adiponectin improved glucose tolerance 60 minutes after injection, whereas normoglycemia in control mice was unaffected. ICV adiponectin increased pAKT, decreased phospho-AMP-activated protein kinase, and did not change phospho-signal transducer and activator of transcription 3 immunoreactivity. In HF-fed mice, ICV adiponectin reversed parameters of hypothalamic inflammation and insulin resistance as determined by the number of phospho-glycogen synthase kinase 3 β(Ser9) and phospho-c-Jun N-terminal kinase (Thr183/Tyr185) immunoreactive cells in the arcuate nucleus and ventromedial hypothalamus. This study demonstrates that the insulin-sensitizing properties of adiponectin are at least partially based on a neuroendocrine mechanism that involves centrally synthesized adiponectin. PMID:24564394

  20. Increased Expression of Angiogenic and Inflammatory Proteins in the Vitreous of Patients with Ischemic Central Retinal Vein Occlusion

    PubMed Central

    Ehlken, Christoph; Grundel, Bastian; Michels, Daniel; Junker, Bernd; Stahl, Andreas; Schlunck, Günther; Hansen, Lutz L.; Feltgen, Nicolas; Martin, Gottfried; Agostini, Hansjürgen T.; Pielen, Amelie

    2015-01-01

    Background Central retinal vein occlusion (CRVO) is a common disease characterized by a disrupted retinal blood supply and a high risk of subsequent vision loss due to retinal edema and neovascular disease. This study was designed to assess the concentrations of selected signaling proteins in the vitreous and blood of patients with ischemic CRVO. Methods Vitreous and blood samples were collected from patients undergoing surgery for ischemic CRVO (radial optic neurotomy (RON), n = 13), epiretinal gliosis or macular hole (control group, n = 13). Concentrations of 40 different proteins were determined by an ELISA-type antibody microarray. Results Expression of proteins enriched in the vitreous (CCL2, IGFBP2, MMP10, HGF, TNFRSF11B (OPG)) was localized by immunohistochemistry in eyes of patients with severe ischemic CRVO followed by secondary glaucoma. Vitreal expression levels were higher in CRVO patients than in the control group (CRVO / control; p < 0.05) for ADIPOQ (13.6), ANGPT2 (20.5), CCL2 (MCP1) (3.2), HGF (4.7), IFNG (13.9), IGFBP1 (14.7), IGFBP2 (1.8), IGFBP3 (4.1), IGFBP4 (1.7), IL6 (10.8), LEP (3.4), MMP3 (4.3), MMP9 (3.6), MMP10 (5.4), PPBP (CXCL7 or NAP2) (11.8), TIMP4 (3.8), and VEGFA (85.3). In CRVO patients, vitreal levels of CCL2 (4.2), HGF (23.3), IGFBP2 (1.23), MMP10 (2.47), TNFRSF11B (2.96), and VEGFA (29.2) were higher than the blood levels (vitreous / blood, p < 0.05). Expression of CCL2, IGFBP2, MMP10, HGF, and TNFRSF11B was preferentially localized to the retina and the retinal pigment epithelium (RPE). Conclusion Proteins related to hypoxia, angiogenesis, and inflammation were significantly elevated in the vitreous of CRVO patients. Moreover, some markers known to indicate atherosclerosis may be related to a basic vascular disease underlying RVO. This would imply that local therapeutic targeting might not be sufficient for a long term therapy in a systemic disease but hypothetically reduce local changes as an initial therapeutic approach. PMID

  1. Neuroprotective and Antiapoptotic Activity of Lineage-Negative Bone Marrow Cells after Intravitreal Injection in a Mouse Model of Acute Retinal Injury

    PubMed Central

    Machalińska, Anna; Pius-Sadowska, Ewa; Kawa, Miłosz P.; Paczkowska, Edyta; Rudnicki, Michał; Lejkowska, Renata; Baumert, Bartłomiej; Wiszniewska, Barbara; Machaliński, Bogusław

    2015-01-01

    We investigated effects of bone marrow-derived, lineage-negative cell (Lin−BMC) transplantation in acute retinal injury. Lin−BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin−BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin−BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin−BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin−BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors. PMID:25810725

  2. Neuroprotective and antiapoptotic activity of lineage-negative bone marrow cells after intravitreal injection in a mouse model of acute retinal injury.

    PubMed

    Machalińska, Anna; Rogińska, Dorota; Pius-Sadowska, Ewa; Kawa, Miłosz P; Paczkowska, Edyta; Rudnicki, Michał; Lejkowska, Renata; Baumert, Bartłomiej; Wiszniewska, Barbara; Machaliński, Bogusław

    2015-01-01

    We investigated effects of bone marrow-derived, lineage-negative cell (Lin(-)BMC) transplantation in acute retinal injury. Lin(-)BMCs were intravitreally injected into murine eyes at 24 h after NaIO3-induced injury. Morphology, function, and expression of apoptosis-related genes, including brain-derived neurotrophic factor (BDNF) and its receptor, were assessed in retinas at 7 days, 28 days, and 3 months after transplantation. Moreover, global gene expression at day 7 was analyzed by RNA arrays. We observed that Lin(-)BMCs integrated into outer retinal layers improving morphological retinal structure and induced molecular changes such as downregulation of proapoptotic caspase-3 gene, a decrease in BAX/BCL-2 gene ratio, and significant elevation of BDNF expression. Furthermore, transplanted Lin(-)BMCs differentiated locally into cells with a macrophage-like phenotype. Finally, Lin(-)BMCs treatment was associated with generation of two distinct transcriptomic patterns. The first relates to downregulated genes associated with regulation of neuron cell death and apoptosis, response to oxidative stress/hypoxia and external stimuli, and negative regulation of cell proliferation. The second relates to upregulated genes associated with neurological system processes and sensory perception. Collectively, our data demonstrate that transplanted Lin(-)BMCs exert neuroprotective function against acute retinal injury and this effect may be associated with their antiapoptotic properties and ability to express neurotrophic factors. PMID:25810725

  3. A Rare Cause of Unilateral Central Retinal Vein Occlusion in a Young Patient: Type III Mixed Cryoglobulinemia

    PubMed Central

    Sekeroglu, Mehmet Ali; Anayol, Mustafa Alpaslan; Yilmazbas, Pelin

    2016-01-01

    Purpose. To report a young male with unilateral central retinal vein occlusion (CRVO) associated with cryoglobulinemia. Case Presentation. A 33-year-old male without any known systemic or ocular disorder was admitted to our clinic with a complaint of visual loss for three days in his left eye. Based on the clinical, laboratory, and ophthalmological assessments, we diagnosed this case as type III mixed cryoglobulinemia with unilateral CRVO with macular edema. For treatment, two intravitreal ranibizumab injections were administered monthly and oral prednisone (64 mg/day) was begun. Subsequently, cryoglobulins became undetectable, macular edema decreased, and the visual acuity improved to 20/32 over an 8-week period. At 24 weeks, the patient's visual acuity remained 20/32 and no recurrence was observed while the patient was still on prednisone (16 mg/day). Conclusion. Cryoglobulinemia should be considered in the differential diagnosis of the patients with CRVO. PMID:27418988

  4. An Unusual Case of Central Retinal Vein Occlusion and Review of the Toxicity Profile of Regorafenib in GIST Patients.

    PubMed

    Schvartsman, Gustavo; Wagner, Michael J; Zobniw, Chrystia M; Trinh, Van Anh; Patel, Shreyaskumar; Somaiah, Neeta

    2016-08-01

    Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract with around 5000 new cases per year. Outcomes for patients with GIST dramatically improved after the development of tyrosine kinase inhibitors targeted against the aberrant signaling pathways that drive GIST oncogenesis. Majority of patients derive benefit from first-line imatinib, and the type of driver mutation is predictive of response. However, almost half of the patients eventually develop resistance to initial targeted therapy and further lines of treatment do not have the same impact. Regorafenib is an oral multi-kinase inhibitor approved as a third-line therapy for advanced GIST and though its efficacy is limited in comparison to imatinib, it has activity across the various driver mutation categories in GIST even in the setting of imatinib resistance. Herein, we describe a case of central retinal vein occlusion (CRVO) secondary to regorafenib and review regorafenib's efficacy and toxicity profile. PMID:27319943

  5. Vision Loss due to Central Retinal Artery Occlusion Following Embolization in a Case of a Giant Juvenile Nasopharyngeal Angiofibroma.

    PubMed

    Trivedi, Mihir; Desai, Roshani J; Potdar, Nayana A; Shinde, Chhaya A; Ukirde, Vivek; Bhuta, Maunil; Nair, Akshay Gopinathan

    2015-07-01

    Juvenile nasopharyngeal angiofibroma (JNA) is a benign, vascular, and locally aggressive tumor that arises in the nasal cavity, extending into the nasopharynx and often in to the orbit. It may rarely present to the ophthalmologist with proptosis and optic neuropathy. Preoperative embolization of JNA is done before surgical resection. In this communication, the authors report a rare occurrence of ipsilateral central retinal artery occlusion (CRAO) following embolization with polyvinyl alcohol in a 13-year-old boy with right-sided JNA. Retrospective review of the angiograms pointed out to a suspicious communication between the external carotid artery and the ophthalmic vessels. Pre-embolization detailed study of the angiograms is necessary to avoid such devastating complications. Although rare, vision loss is a possible complication arising from embolization of nasopharyngeal and intracranial tumors, and all patients undergoing these procedures should be informed of the risk of visual loss because it has a lasting impact on the quality of life. PMID:26167999

  6. Centrally Administered Ghrelin Acutely Influences Food Choice in Rodents.

    PubMed

    Schéle, Erik; Bake, Tina; Rabasa, Cristina; Dickson, Suzanne L

    2016-01-01

    We sought to determine whether the orexigenic hormone, ghrelin, is involved in the intrinsic regulation of food choice in rats. Ghrelin would seem suited to serve such a role given that it signals hunger information from the stomach to brain areas important for feeding control, including the hypothalamus and reward system (e.g. ventral tegmental area, VTA). Thus, in rats offered a choice of palatable foods (sucrose pellets and lard) superimposed on regular chow for 2 weeks, we explored whether acute central delivery of ghrelin (intracerebroventricular (ICV) or intra-VTA) is able to redirect their dietary choice. The major unexpected finding is that, in rats with high baseline lard intake, acute ICV ghrelin injection increased their chow intake over 3-fold, relative to vehicle-injected controls, measured at both 3 hr and 6 hr after injection. Similar effects were observed when ghrelin was delivered to the VTA, thereby identifying the VTA as a likely contributing neurobiological substrate for these effects. We also explored food choice after an overnight fast, when endogenous ghrelin levels are elevated, and found similar effects of dietary choice to those described for ghrelin. These effects of fasting on food choice were suppressed in models of suppressed ghrelin signaling (i.e. peripheral injection of a ghrelin receptor antagonist to rats and ghrelin receptor (GHSR) knock-out mice), implicating a role for endogenous ghrelin in the changes in food choice that occur after an overnight fast. Thus, in line with its role as a gut-brain hunger hormone, ghrelin appears to be able to acutely alter food choice, with notable effects to promote "healthy" chow intake, and identify the VTA as a likely contributing neurobiological substrate for these effects. PMID:26925974

  7. Centrally Administered Ghrelin Acutely Influences Food Choice in Rodents

    PubMed Central

    Schéle, Erik; Bake, Tina; Rabasa, Cristina; Dickson, Suzanne L.

    2016-01-01

    We sought to determine whether the orexigenic hormone, ghrelin, is involved in the intrinsic regulation of food choice in rats. Ghrelin would seem suited to serve such a role given that it signals hunger information from the stomach to brain areas important for feeding control, including the hypothalamus and reward system (e.g. ventral tegmental area, VTA). Thus, in rats offered a choice of palatable foods (sucrose pellets and lard) superimposed on regular chow for 2 weeks, we explored whether acute central delivery of ghrelin (intracerebroventricular (ICV) or intra-VTA) is able to redirect their dietary choice. The major unexpected finding is that, in rats with high baseline lard intake, acute ICV ghrelin injection increased their chow intake over 3-fold, relative to vehicle-injected controls, measured at both 3 hr and 6 hr after injection. Similar effects were observed when ghrelin was delivered to the VTA, thereby identifying the VTA as a likely contributing neurobiological substrate for these effects. We also explored food choice after an overnight fast, when endogenous ghrelin levels are elevated, and found similar effects of dietary choice to those described for ghrelin. These effects of fasting on food choice were suppressed in models of suppressed ghrelin signaling (i.e. peripheral injection of a ghrelin receptor antagonist to rats and ghrelin receptor (GHSR) knock-out mice), implicating a role for endogenous ghrelin in the changes in food choice that occur after an overnight fast. Thus, in line with its role as a gut-brain hunger hormone, ghrelin appears to be able to acutely alter food choice, with notable effects to promote “healthy” chow intake, and identify the VTA as a likely contributing neurobiological substrate for these effects. PMID:26925974

  8. Time-dependent retinal ganglion cell loss, microglial activation and blood-retina-barrier tightness in an acute model of ocular hypertension.

    PubMed

    Trost, A; Motloch, K; Bruckner, D; Schroedl, F; Bogner, B; Kaser-Eichberger, A; Runge, C; Strohmaier, C; Klein, B; Aigner, L; Reitsamer, H A

    2015-07-01

    Glaucoma is a group of neurodegenerative diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons, and is the second leading cause of blindness worldwide. Elevated intraocular pressure is a well known risk factor for the development of glaucomatous optic neuropathy and pharmacological or surgical lowering of intraocular pressure represents a standard procedure in glaucoma treatment. However, the treatment options are limited and although lowering of intraocular pressure impedes disease progression, glaucoma cannot be cured by the currently available therapy concepts. In an acute short-term ocular hypertension model in rat, we characterize RGC loss, but also microglial cell activation and vascular alterations of the retina at certain time points. The combination of these three parameters might facilitate a better evaluation of the disease progression, and could further serve as a new model to test novel treatment strategies at certain time points. Acute ocular hypertension (OHT) was induced by the injection of magnetic microbeads into the rat anterior chamber angle (n = 22) with magnetic position control, leading to constant elevation of IOP. At certain time points post injection (4d, 7d, 10d, 14d and 21d), RGC loss, microglial activation, and microvascular pericyte (PC) coverage was analyzed using immunohistochemistry with corresponding specific markers (Brn3a, Iba1, NG2). Additionally, the tightness of the retinal vasculature was determined via injections of Texas Red labeled dextran (10 kDa) and subsequently analyzed for vascular leakage. For documentation, confocal laser-scanning microscopy was used, followed by cell counts, capillary length measurements and morphological and statistical analysis. The injection of magnetic microbeads led to a progressive loss of RGCs at the five time points investigated (20.07%, 29.52%, 41.80%, 61.40% and 76.57%). Microglial cells increased in number and displayed an activated morphology

  9. Damage patterns of retinal nerve fiber layer in acute and chronic intraocular pressure elevation in primary angle closure glaucoma

    PubMed Central

    Liu, Xing; Li, Mei; Zhong, Yi-Min; Xiao, Hui; Huang, Jing-Jing; Kong, Xiang-Yun

    2010-01-01

    AIM To observe the differences of damage patterns of retinal nerve fiber layer (RNFL) between acute and chronic intraocular pressure (IOP) elevation in primary angle closure glaucoma (PACG) using optical coherence tomography (OCT). METHODS Twenty-four patients (48 eyes) with unilateral acute PACG (APACG) attack in the 6 months after admission and 36 patients (64 eyes) with chronic PACG (CPACG) were included in this prospective study. For all cases, IOP has been controlled under 21mmHg after treatment. Using stratus OCT, the RNFL thickness was assessed in eyes with PACG within 3 days, 2 weeks, 1, 3 and 6 months after IOP was controlled. Repeated measures ANOVA was used to examine the changes of RNFL thickness at different time after IOP being controlled in both acute attack eyes and unaffected fellow eyes of APACG and eyes with CPACG. RESULTS The mean RNFL thickness for the APACG-attacked eyes increased significantly within 3 days (121.49±23.84)µm after acute onset and then became thinner along with time [(107.22±24.72)µm at 2 weeks,(93.58±18.37)µm at 1 month, (84.10±19.89)µm at 3 months and (78.98±19.17)µm at 6 months]. In APACG-attacked eyes, there were significant differences of average RNFL thickness at 5 different times after IOP was controlled (P<0.001). In the APACG unaffected fellow eyes and CPACG eyes, there were no significant differences in mean RNFL thickness at 5 different times(F=0.450, P=0.104 in APACG unaffected fellow eyes and F=1.558, P=0.200 in CPACG eyes). There was significant difference for interaction between time periods and groups (F=1.912, P=0.003). CONCLUSION RNFL damage patterns are different under different IOP elevated courses. In APACG, RNFL was found to be swollen and thickening right after acute attack and then becomes thinning and atrophy along with the time, while RNFL was found to be diffused thinness in CPACG. PMID:22553541

  10. Predictors of short-term outcomes related to central subfield foveal thickness after intravitreal bevacizumab for macular edema due to central retinal vein occlusion

    PubMed Central

    Wang, Mei-Zi; Feng, Kang; Lu, Yao; Qian, Fang; Lu, Xin-Rong; Zang, Si-Wen; Zhao, Lin

    2016-01-01

    AIM To investigate the predictive factors for short-term effects of intravitreal bevacizumab injections on central subfield foveal thickness (CSFT) in patients with macular edema (ME) secondary to central retinal vein occlusion (CRVO). METHODS This was a retrospective study in 60 eyes treated with intravitreal bevacizumab injections for ME due to CRVO. Follow-up was three months. The Early Treatment Diabetic Retinopathy Study (ETDRS) score and CSFT measured by spectral-domain optical coherence tomography (SD-OCT) were used to observe the changes in best-corrected visual acuity (BCVA). Baseline BCVA, CSFT, age, CRVO duration and the presence of cystoid macular edema (CME) or subretinal fluid (SRF) were analyzed as potential predictive factors of the effects of intravitreal bevacizumab injections. RESULTS BCVA improved from 0.9 logMAR at baseline to 0.6 logMAR at 3mo, which was associated with a significant reduction in CSFT from 721 µm to 392 µm 3mo after injection. About 50% of CME cases and more than 90% of SRF cases responded to treatment with a complete resolution at 3mo. Age (P=0.036) and low baseline CSFT (P=0.037) were associated with a good 3-month prognosis. Patients >60 years old achieved better CME resolution (P=0.031) and lower CSFT at 3mo (305 µm vs 474 µm, P=0.003). CONCLUSION Intravitreal bevacizumab significantly improved visual acuity and CSFT in patients with CRVO after 3mo. Older age and lower baseline CSFT were good predictors of short-term CSFT outcomes. The retinal thickness response to bevacizumab might depend on the resolution of CME rather than SRF. PMID:26949616

  11. Centrally administered naloxone blocks reflex natriuresis after acute unilateral nephrectomy.

    PubMed

    Lin, S Y; Humphreys, M H

    1985-09-01

    Acute unilateral nephrectomy (AUN) leads to a natriuresis and kaliuresis by the remaining kidney through reflex mechanisms involving opiate receptors. To determine whether the opiate receptors mediating these responses are located in the central nervous system, we carried out AUN in anesthetized rats undergoing continuous ventriculocisternal perfusion (VCP) with artificial cerebrospinal fluid (CSF). AUN caused large increases in both Na (UNaV) and K (UKV) excretion without changes in glomerular filtration rate or arterial blood pressure. When the opiate receptor antagonist naloxone was added to the perfusate to achieve a perfusion rate of 32 micrograms X kg-1 X h-1, AUN failed to increase either UNaV or UKV by the remaining kidney. This dose of naloxone, however, was without effect when infused intravenously. Addition of thyrotropin-releasing hormone (TRH) to the artificial CSF to achieve a VCP rate of 50 micrograms X kg-1 X h-1 also blocked the expected increase in UNaV and UKV by the remaining kidney after AUN. Infusion of TRH intravenously at the same rate did not interfere with the postnephrectomy natriuresis or kaliuresis. Higher intravenous infusion rates of TRH (1 and 2 mg X kg-1h-1) prevented the postnephrectomy natriuresis without affecting the kaliuresis. These results indicate that the effect of naloxone to block the reflex natriuresis and kaliuresis after AUN resides largely in the central nervous system. The blockade by naloxone of the postnephrectomy natriuresis is duplicated by centrally administered TRH, providing another example of the interaction of this hormone with the endogenous opioid system. Large intravenous infusions of TRH also block the postnephrectomy natriuresis but not the kaliuresis. PMID:3929623

  12. Retinal pathways influence temporal niche

    PubMed Central

    Doyle, Susan E.; Yoshikawa, Tomoko; Hillson, Holly; Menaker, Michael

    2008-01-01

    In mammals, light input from the retina entrains central circadian oscillators located in the suprachiasmatic nuclei (SCN). The phase of circadian activity rhythms with respect to the external light:dark cycle is reversed in diurnal and nocturnal species, although the phase of SCN rhythms relative to the light cycle remains unchanged. Neural mechanisms downstream from the SCN are therefore believed to determine diurnality or nocturnality. Here, we report a switch from nocturnal to diurnal entrainment of circadian activity rhythms in double-knockout mice lacking the inner-retinal photopigment melanopsin (OPN4) and RPE65, a key protein used in retinal chromophore recycling. These mice retained only a small amount of rod function. The change in entrainment phase of Rpe65−/−;Opn4−/− mice was accompanied by a reversal of the rhythm of clock gene expression in the SCN and a reversal in acute masking effects of both light and darkness on activity, suggesting that the nocturnal to diurnal switch is due to a change in the neural response to light upstream from the SCN. A switch from nocturnal to diurnal activity rhythms was also found in wild-type mice transferred from standard intensity light:dark cycles to light:dark cycles in which the intensity of the light phase was reduced to scotopic levels. These results reveal a novel mechanism by which changes in retinal input can mediate acute temporal-niche switching. PMID:18695249

  13. One-year outcome of bevacizumab therapy for chronic macular edema in central and branch retinal vein occlusions in real-world clinical practice in the UK

    PubMed Central

    Lip, Peck Lin; Malick, Huzaifa; Damer, Kenan; Elsherbiny, Samer; Darrad, Kanupriya M; Mushtaq, Bushra; Mitra, Arijit; Stavrou, Panagiota; Yang, Yit

    2015-01-01

    Background The purpose of this study was to investigate the 12-month outcome of macular edema secondary to both chronic and new central and branch retinal vein occlusions treated with intravitreal bevacizumab in the real-life clinical setting in the UK. Methods Retrospective case notes analysis of consecutive patients with retinal vein occlusions treated with bevacizumab in 2010 to 2012. Outcome measures were visual acuity (measured with Snellen, converted into logMAR [logarithm of the minimum angle of resolution] for statistical calculation) and central retinal thickness at baseline, 4 weeks post-loading phase, and at 1 year. Results There were 56 and 100 patients with central and branch retinal vein occlusions, respectively, of whom 62% had chronic edema and received prior therapies and another 32% required additional laser treatments post-baseline bevacizumab. Baseline median visual acuity was 0.78 (interquartile range [IQR] 0.48–1.22) in the central group and 0.6 (IQR 0.3–0.78) in the branch group. In both groups, visual improvement was statistically significant from baseline compared to post-loading (P<0.001 and P=0.03, respectively), but was not significant by month 12 (P=0.058 and P=0.166, respectively); 30% improved by at least three lines and 44% improved by at least one line by month 12. Baseline median central retinal thickness was 449 μm (IQR 388–553) in the central group and 441 μm (IQR 357–501) in the branch group. However, the mean reduction in thickness was statistically significant at post-loading (P<0.001) and at the 12-month time point (P<0.001) for both groups. The average number of injections in 1 year was 4.2 in the central group and 3.3 in the branch group. Conclusion Our large real-world cohort results indicate that bevacizumab introduced to patients with either new or chronic edema due to retinal vein occlusion can result in resolution of edema and stabilization of vision in the first year. PMID:26445525

  14. Central Glaucomatous Damage of the Macula Can Be Overlooked by Conventional OCT Retinal Nerve Fiber Layer Thickness Analyses

    PubMed Central

    Wang, Diane L.; Raza, Ali S.; de Moraes, Carlos Gustavo; Chen, Monica; Alhadeff, Paula; Jarukatsetphorn, Ravivarn; Ritch, Robert; Hood, Donald C.

    2015-01-01

    Purpose To assess the extent to which glaucomatous damage of the macula can be detected using the summary statistics of a commercial report based upon the circumpapillary retinal nerve fiber layer (cpRNFL) thickness obtained with frequency domain optical coherence tomography (fdOCT). Methods One hundred forty-three eyes of 143 open-angle glaucoma patients and suspects (56.4 ± 13.8 years) had 10-2 visual fields (VFs) and fdOCT macular and disc cube scans. RNFL and retinal ganglion cell plus inner plexiform layer thickness and probability maps were generated and combined with 10-2 VF information in a single-page, custom report previously described. Three graders evaluated these reports and classified each eye as “abnormal macula” or “normal macula.” Commercially available fdOCT reports for cpRNFL thickness were generated using the automatic segmentation algorithm and norms from the machine. The ability of the reports to detect macular damage was analyzed in three ways: temporal quadrant (TQ) < 5%; TQ < 5% or clock hour 7 < 1% (TQ + CH7); and clock hours 7 through 10 with two sectors < 5% or one sector < 1% (CH7−10). Results Sixty-one (43%) eyes were classified “abnormal macula” and 41 (29%) as “normal macula”; the 10-2 VFs and OCT probability maps did not agree in the remaining eyes. Of the 61 abnormal eyes, the TQ criterion missed 47 (77%); TQ + CH7 missed 24 (39%); and CH7−10 missed 22 (36%). Conclusions Conventional cpRNFL analyses on commercial OCT reports can miss macular (central field) damage. Translational Relevance To detect glaucomatous damage of the macula, additional tests, such as macular cube scans and/or 10-2 VFs, should be performed. PMID:26644964

  15. The effect of an acute increase in central blood volume on the response of cerebral blood flow to acute hypotension.

    PubMed

    Ogoh, Shigehiko; Hirasawa, Ai; Sugawara, Jun; Nakahara, Hidehiro; Ueda, Shinya; Shoemaker, J Kevin; Miyamoto, Tadayoshi

    2015-09-01

    The purpose of the present study was to examine whether the response of cerebral blood flow to an acute change in perfusion pressure is modified by an acute increase in central blood volume. Nine young, healthy subjects voluntarily participated in this study. To measure dynamic cerebral autoregulation during normocapnic and hypercapnic (5%) conditions, the change in middle cerebral artery mean blood flow velocity was analyzed during acute hypotension caused by two methods: 1) thigh-cuff occlusion release (without change in central blood volume); and 2) during the recovery phase immediately following release of lower body negative pressure (LBNP; -50 mmHg) that initiated an acute increase in central blood volume. In the thigh-cuff occlusion release protocol, as expected, hypercapnia decreased the rate of regulation, as an index of dynamic cerebral autoregulation (0.236 ± 0.018 and 0.167 ± 0.025 s(-1), P = 0.024). Compared with the cuff-occlusion release, the acute increase in central blood volume (relative to the LBNP condition) with LBNP release attenuated dynamic cerebral autoregulation (P = 0.009). Therefore, the hypercapnia-induced attenuation of dynamic cerebral autoregulation was not observed in the LBNP release protocol (P = 0.574). These findings suggest that an acute change in systemic blood distribution modifies dynamic cerebral autoregulation during acute hypotension. PMID:26159757

  16. Retinal vein occlusion and the risk of acute myocardial infarction development: a 12-year nationwide cohort study

    PubMed Central

    Rim, Tyler Hyungtaek; Han, John Seungsoo; Oh, Jaewon; Kim, Dong Wook; Kang, Seok-Min; Chung, Eun Jee

    2016-01-01

    The goal of this study was to evaluate the risk of developing acute myocardial infarction (AMI) following retinal vein occlusion (RVO). A retrospective cohort study was performed from the National Health Insurance Service and comprised 1,025,340 random subjects who were followed from 2002 to 2013. Patients with RVO in 2002 were excluded. The RVO group was composed of patients who received an initial RVO diagnosis between January 2003 and December 2007 (n = 1677). The comparison group was selected (five patients per RVO patient; n = 8367) using propensity score matching according to sociodemographic factors and the year of enrolment. Each patient was tracked until 2013. The Cox proportional hazard regression model was used. AMI developed in 7.6% of the RVO group and 5.3% of the comparison group (p < 0.001) for 7.7 median follow-up periods. RVO increased the risk of AMI development [hazard ratio (HR) = 1.25; 95% Confidence Interval (CI) 1.02 to 1.52]. In the subgroup analysis, RVO patients aged <65 years and the males within this age group had an adjusted HR of 1.47 (95% CI 1.10 to 1.98) and an adjusted HR of 2.00 (95% CI 1.38 to 2.91) for AMI development, respectively. RVO was significantly associated with AMI development. PMID:26924150

  17. Hyperglycemia attenuates acute permeability response to advanced glycation end products in retinal microvasculature.

    PubMed

    Warboys, C M; Fraser, P A

    2010-07-01

    Increased microvascular permeability contributes to the development of diabetic retinopathy and is associated with hyperglycemia and accumulation of advanced glycation end products (AGEs). The isolated perfused retina preparation was used to investigate the effects of hyperglycemia (HG) on the permeability response to AGEs. Retinae were dissected from rats, and the vasculature perfused with sulforhodamine B fluorescent dye and permeability of venular capillaries was determined from the rate of decrease of fluorescence gradient across a vessel during stasis. The resting permeability was very high in streptozotocin treated and some obese Zucker fatty diabetic rats, but low in others. The permeability response to glycated albumin (which is free radical-dependent) in these animals was reduced for a range of concentrations compared to the lean controls. The effects of 15 min 25 mM glucose (HG) superfusion on the retinal microvascular permeability response to 5 microM AGE-BSA was studied in non-diabetic Wistar rats. HG itself had no effect on permeability, but reduced the response to AGE-BSA from 1.02+/-0.08x10(-6) cm s(-1) to 0.31+/-0.07x10(-6) cm s(-1). The response to bradykinin (also free radical-dependent) was not affected by HG. This suggests that chronic exposure to HG down-regulates the signalling pathways activated in response to RAGE stimulation. PMID:20302881

  18. Receptor mediated disruption of retinal pigment epithelium function in acute glycated-albumin exposure.

    PubMed

    Dahrouj, Mohammad; Desjardins, Danielle M; Liu, Yueying; Crosson, Craig E; Ablonczy, Zsolt

    2015-08-01

    Diabetic macular edema (DME) is a major cause of visual impairment. Although DME is generally believed to be a microvascular disease, dysfunction of the retinal pigment epithelium (RPE) can also contribute to its development. Advanced glycation end-products (AGE) are thought to be one of the key factors involved in the pathogenesis of diabetes in the eye, and we have previously demonstrated a rapid breakdown of RPE function following glycated-albumin (Glyc-alb, a common AGE mimetic) administration in monolayer cultures of fetal human RPE cells. Here we present new evidence that this response is attributed to apically oriented AGE receptors (RAGE). Moreover, time-lapse optical coherence tomography in Dutch-belted rabbits 48 h post intravitreal Glyc-alb injections demonstrated a significant decrease in RPE-mediated fluid resorption in vivo. In both the animal and tissue culture models, the response to Glyc-alb was blocked by the relatively selective RAGE antagonist, FPS-ZM1 and was also inhibited by ZM323881, a relatively selective vascular endothelial growth factor receptor 2 (VEGF-R2) antagonist. Our data establish that the Glyc-alb-induced breakdown of RPE function is mediated via specific RAGE and VEGF-R2 signaling both in vitro and in vivo. These results are consistent with the notion that the RPE is a key player in the pathogenesis of DME. PMID:26070987

  19. [Application of retinal oximeter in ophthalmology].

    PubMed

    Li, Jing; Ma, Jianmin; Wang, Ningli

    2015-11-01

    Retinal oximeter is a new machine which has been used in the diagnose, treatment and research of several ophthalmic diseases for recent years. It allows ophthalmologists to gain retinal oxygen saturation directly. Therefore, retinal oximeter might be useful for ophthalmologists to understand ophthalmic diseases more deeper and clarify the impact of ischemia on retinal function. It has been reported in the literatures that retinal oximeter has potentially useful diagnostic and therapeutic indications in various eye diseases such as diabetic retinopathy, central retinal vein and artery occlusion, retinitis pigmentosa, glaucomatous optic neuropathy, et al. In this thesis, the application of retinal oximeter in ophthalmology is reviewed. PMID:26850588

  20. Assessment of Central Retinal Sensitivity Employing Two Types of Microperimetry Devices

    PubMed Central

    Liu, Hongting; Bittencourt, Millena G.; Wang, Jiangxia; Sophie, Raafay; Annam, Rachel; Ibrahim, Mohamed A.; Sepah, Yasir J.; Moradi, Ahmadreza; Scholl, Hendrik P. N.; Nguyen, Quan Dong

    2014-01-01

    Purpose To compare the retinal sensitivity measurements obtained with two microperimeters, the Micro-Perimeter 1 (MP-1) and the Optos optical coherence tomography (OCT)/scanning laser ophthalmoscope (SLO) in subjects with and without maculopathies. Methods Forty-five eyes with no known ocular disease and 47 eyes with maculopathies were examined using both microperimeters. A contrast-adjusted scale was applied to resolve the different stimuli and background luminance existing between the two devices. Results There was a strong ceiling effect with the MP-1 in the healthy group, with 90.1% (1136 of 1260) test points clustered at 20 dB. The mean sensitivity for the corresponding points in the OCT/SLO was 25.8 ± 1.9 dB. A floor effect was also observed with the OCT/SLO in the maculopathy group with 9.7% (128 of 1316) points clustered at 9-dB values. The corresponding mean sensitivity in the MP-1 was 1.7 ± 3.9 dB. A regression equation between the two microperimeters was established in the common 10 to19 dB intervals as: OCT/SLO = 15.6 + 0.564 × MP-1 − 0.009 × MP-12 + k (k is an individual point constant; MP-1 coefficient P < 0.001; MP-12 coefficient P = 0.006). Conclusion The OCT/SLO and the MP-1 provide two different ranges of contrasts for microperimetry examination. Broadening the dynamic range may minimize the constraint of the ceiling and floor effect. There is a significant mathematical relationship in the common interval of the contrast scale. Translational Relevance Applying a unified and broadened dynamic range in different types of microperimeters will help to generate consistent clinical reference for measurements. PMID:25237592

  1. Acute posterior multifocal placoid pigment epitheliopathy-retinal "white dot syndrome".

    PubMed

    Grković, Desanka; Oros, Ana; Bedov, Tatjana; Karadžić, Jelena; Gvozdenović, Ljiljana; Jovanović, Sandra

    2013-02-01

    Acute posterior multifocal placoid pigment epitheliopathy- APMPPE is an acquired idiopathic inflammatory disease of the chorioretina. This case report presents a typical clinical manifestation of a very rare condition: a twenty ive-year old female complained of a sudden bilateral decrease of vision. She reported lu-like symptoms and taking antibiotics therapy. Fundus examination revealed numerous discrete yellow-white lesions at posterior pole involving the macula. After a period of 7 days oral prednisone treatment she was completely recovered. Usage of steroids is recommended for treating APMPPE in cases where macula is involved and in recurrent cases. PMID:23348193

  2. Resolution of Persistent Cystoid Macular Edema due to Central Retinal Vein Occlusion in a Vitrectomized Eye following Intravitreal Implant of Dexamethasone 0.7 mg

    PubMed Central

    Reibaldi, Michele; Russo, Andrea; Zagari, Marco; Toro, Mario; Grande De, Vittorio; Cifalinò, Valentina; Rametta, Stefania; Faro, Salvatore; Longo, Antonio

    2012-01-01

    We report the case of a 62-year-old woman with a history of vitreoretinal surgery for vitreous hemorrhage secondary to central retinal vein occlusion (CRVO). Because of the persistence of macular edema (ME), she received 2 intravitreal injections of bevacizumab 0.5 mg (Avastin®, Genentech/Roche) three months after vitrectomy, without functional or anatomical improvement. Six months after vitrectomy, she therefore received an intravitreal implant of dexamethasone 0.7 mg (Ozurdex®). An improvement in her best-corrected visual acuity and central macular thickness, as measured by optical coherence tomography, was detected 7 days after the injection, and complete resolution of the ME and retinal hemorrhages was observed 6 months after the injection. Dexamethasone intravitreal implant might be an effective treatment option in ME secondary to CRVO, also in vitrectomized eyes. PMID:22615698

  3. VANISHING RETINAL DETACHMENT

    PubMed Central

    2015-01-01

    Purpose: The purpose of this report is to describe a case of rhegmatogenous retinal detachment in the setting of chronic kidney disease that exhibited complete retinal reattachment after serial hemodialysis. Methods: Retrospective case report. Results: A 58-year-old woman with acute vision loss was found to have a macula-involving rhegmatogenous retinal detachment. Due to chronic kidney disease, she continued with routinely scheduled hemodialysis for 1 week until surgical clearance was obtained. Preoperative examination revealed complete reattachment of the retina with a persistent retinal tear. Barrier laser was applied to the tear and the retina remained attached until the most recent follow-up 8 months later. The workup of alternate etiologies was unrevealing. Conclusion: This case describes a temporal association between hemodialysis and resolution of subretinal fluid due to rhegmatogenous retinal detachment. A potential causal linkage is suggested based on shifting fluid dynamics associated with hemodialysis. A shift in treatment paradigm is not advised. PMID:26352323

  4. Interventions for asymptomatic retinal breaks and lattice degeneration for preventing retinal detachment

    PubMed Central

    Wilkinson, Charles P

    2015-01-01

    Background Asymptomatic retinal breaks and lattice degeneration are visible lesions that are risk factors for later retinal detachment. Retinal detachments occur when fluid in the vitreous cavity passes through tears or holes in the retina and separates the retina from the underlying retinal pigment epithelium. Creation of an adhesion surrounding retinal breaks and lattice degeneration, with laser photocoagulation or cryotherapy, has been recommended as an effective means of preventing retinal detachment. This therapy is of value in the management of retinal tears associated with the symptoms of flashes and floaters and persistent vitreous traction upon the retina in the region of the retinal break, because such symptomatic retinal tears are associated with a high rate of progression to retinal detachment. Retinal tears and holes unassociated with acute symptoms and lattice degeneration are significantly less likely to be the sites of retinal breaks that are responsible for later retinal detachment. Nevertheless, treatment of these lesions frequently is recommended, in spite of the fact that the effectiveness of this therapy is unproven. Objectives The objective of this review was to assess the effectiveness and safety of techniques used to treat asymptomatic retinal breaks and lattice degeneration for the prevention of retinal detachment. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to February 2014), EMBASE (January 1980 to February 2014), PubMed (January 1948 to February 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in

  5. Cytomegalovirus retinitis

    MedlinePlus

    ... to prevent its return. Alternative Names Cytomegalovirus retinitis Images Eye CMV retinitis CMV (cytomegalovirus) References Crumpacker CS. ... 5. Read More Antibody HIV/AIDS Immune response Retinal detachment Systemic WBC count Update Date 12/10/ ...

  6. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells

    PubMed Central

    Di Lauro, Salvatore; Rodriguez-Crespo, David; Gayoso, Manuel J.; Garcia-Gutierrez, Maria T.; Pastor, J. Carlos; Srivastava, Girish K.

    2016-01-01

    Purpose To develop and standardize a novel organ culture model using porcine central neuroretina explants and RPE cells separated by a cell culture membrane. Methods RPE cells were isolated from porcine eyes, expanded, and seeded on the bottom of cell culture inserts. Neuroretina explants were obtained from the area centralis and cultured alone (controls) on cell culture membranes or supplemented with RPE cells in the same wells but physically separated by the culture membrane. Finally, cellular and tissue specimens were processed for phase contrast, cyto-/histological, and immunochemical evaluation. Neuroretina thickness was also determined. Results Compared to the neuroretinas cultured alone, the neuroretinas cocultured with RPE cells maintained better tissue structure and cellular organization, displayed better preservation of photoreceptors containing rhodopsin, lower levels of glial fibrillary acidic protein immunoexpression, and preservation of cellular retinaldehyde binding protein both markers of reactive gliosis. Neuroretina thickness was significantly greater in the cocultures. Conclusions A coculture model of central porcine neuroretina and RPE cells was successfully developed and standardized. This model mimics a subretinal space and will be useful in studying interactions between the RPE and the neuroretina and to preclinically test potential therapies. PMID:27081295

  7. Effects of central opiate and serotoninergic structures on heart rhythm during acute myocardial ischemia.

    PubMed

    Prokop'eva, E V; Pivovarov, Y I

    2001-12-01

    Electrostimulation of the central gray matter in the sylvian aqueduct and nucleus raphe magnus produced an antiarrhythmic effect during acute myocardial ischemia. Stimulation and blockade of opiate receptors in the central amygdaloid nucleus and lateral hypothalamus with dalargin and naloxone induced the same effect. Destruction of the central gray matter in the sylvian aqueduct and nucleus raphe magnus decreased electrical stability of ischemic myocardium. PMID:12152875

  8. [New drug VEGF Trap-Eye--Eylea--and its use in the treatment of age-related macular degeneration, central retinal vein occlusion, diabetic macular edema, and choroidal neovascularization secondary to pathologic myopia].

    PubMed

    Rejdak, Robert; Szkaradek, Małgorzata; Taslaq, Wesam; Kałuzny, Jakub J; Grieb, Pawel; Jünemann, Anselm G M

    2012-01-01

    Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of choroidal and retinal neovascularization. Anti-VEGF therapy changed the standard-of-care for ocular disease with neovascularisation. This article presents one promising new drug--VEGF Trap-Eye--and results of clinical trials evaluating its efficacy in the treatment of wet age-related macular degeneration, central retinal vain occlusion, diabetic macular edema and choroidal neovascularization secondary to pathologic myopia. PMID:23461161

  9. Blocking Neurogenic Inflammation for the Treatment of Acute Disorders of the Central Nervous System

    PubMed Central

    Lewis, Kate Marie; Turner, Renée Jade

    2013-01-01

    Classical inflammation is a well-characterized secondary response to many acute disorders of the central nervous system. However, in recent years, the role of neurogenic inflammation in the pathogenesis of neurological diseases has gained increasing attention, with a particular focus on its effects on modulation of the blood-brain barrier BBB. The neuropeptide substance P has been shown to increase blood-brain barrier permeability following acute injury to the brain and is associated with marked cerebral edema. Its release has also been shown to modulate classical inflammation. Accordingly, blocking substance P NK1 receptors may provide a novel alternative treatment to ameliorate the deleterious effects of neurogenic inflammation in the central nervous system. The purpose of this paper is to provide an overview of the role of substance P and neurogenic inflammation in acute injury to the central nervous system following traumatic brain injury, spinal cord injury, stroke, and meningitis. PMID:23819099

  10. Retinitis Pigmentosa.

    ERIC Educational Resources Information Center

    Carr, Ronald E.

    1979-01-01

    The author describes the etiology of retinitis pigmentosa, a visual dysfunction which results from progressive loss of the retinal photoreceptors. Sections address signs and symptoms, ancillary findings, heredity, clinical diagnosis, therapy, and research. (SBH)

  11. Acute pesticide poisoning and pesticide registration in Central America

    SciTech Connect

    Wesseling, Catharina . E-mail: cwesseli@una.ac.cr; Corriols, Marianela; Bravo, Viria

    2005-09-01

    The International Code of Conduct on the Distribution and Use of Pesticides of the Food and Agriculture Organization (FAO) of the United Nations has been for 20 years the most acknowledged international initiative for reducing negative impact from pesticide use in developing countries. We analyzed pesticide use and poisoning in Central America, particularly in Costa Rica and Nicaragua, and evaluated whether registration decisions are based on such data, in accordance with the FAO Code. Extensive use of very hazardous pesticides continues in Central America and so do poisonings with organophosphates, carbamates, endosulfan and paraquat as the main causative agents. Central American governments do not carry out or commission scientific risk assessments. Instead, guidelines from international agencies are followed for risk management through the registration process. Documentation of pesticide poisonings during several decades never induced any decision to ban or restrict a pesticide. However, based on the official surveillance systems, in 2000, the ministers of health of the seven Central American countries agreed to ban or restrict twelve of these pesticides. Now, almost 4 years later, restrictions have been implemented in El Salvador and in Nicaragua public debate is ongoing. Chemical and agricultural industries do not withdraw problematic pesticides voluntarily. In conclusion, the registration processes in Central America do not comply satisfactorily with the FAO Code. However, international regulatory guidelines are important in developing countries, and international agencies should strongly extend its scope and influence, limiting industry involvement. Profound changes in international and national agricultural policies, steering towards sustainable agriculture based on non-chemical pest management, are the only way to reduce poisonings.

  12. Acute pesticide poisoning and pesticide registration in Central America.

    PubMed

    Wesseling, Catharina; Corriols, Marianela; Bravo, Viria

    2005-09-01

    The International Code of Conduct on the Distribution and Use of Pesticides of the Food and Agriculture Organization (FAO) of the United Nations has been for 20 years the most acknowledged international initiative for reducing negative impact from pesticide use in developing countries. We analyzed pesticide use and poisoning in Central America, particularly in Costa Rica and Nicaragua, and evaluated whether registration decisions are based on such data, in accordance with the FAO Code. Extensive use of very hazardous pesticides continues in Central America and so do poisonings with organophosphates, carbamates, endosulfan and paraquat as the main causative agents. Central American governments do not carry out or commission scientific risk assessments. Instead, guidelines from international agencies are followed for risk management through the registration process. Documentation of pesticide poisonings during several decades never induced any decision to ban or restrict a pesticide. However, based on the official surveillance systems, in 2000, the ministers of health of the seven Central American countries agreed to ban or restrict twelve of these pesticides. Now, almost 4 years later, restrictions have been implemented in El Salvador and in Nicaragua public debate is ongoing. Chemical and agricultural industries do not withdraw problematic pesticides voluntarily. In conclusion, the registration processes in Central America do not comply satisfactorily with the FAO Code. However, international regulatory guidelines are important in developing countries, and international agencies should strongly extend its scope and influence, limiting industry involvement. Profound changes in international and national agricultural policies, steering towards sustainable agriculture based on non-chemical pest management, are the only way to reduce poisonings. PMID:16153991

  13. Changes of central haemodynamic parameters during mental stress and acute bouts of static and dynamic exercise.

    PubMed

    Lydakis, C; Momen, A; Blaha, C; Gugoff, S; Gray, K; Herr, M; Leuenberger, U A; Sinoway, L I

    2008-05-01

    Chronic dynamic (aerobic) exercise decreases central arterial stiffness, whereas chronic resistance exercise evokes the opposite effect. Nevertheless, there is little information available on the effects of acute bouts of exercise. Also, there is limited data showing an increase of central arterial stiffness during acute mental stress. This study aimed to determine the effect of acute mental and physical (static and dynamic exercise) stress on indices of central arterial stiffness. Fifteen young healthy volunteers were studied. The following paradigms were performed: (1) 2 min of mental arithmetic, (2) short bouts (20 s) of static handgrip at 20 and 70% of maximal voluntary contraction (MVC), (3) fatiguing handgrip at 40% MVC and (4) incremental dynamic knee extensor exercise. Central aortic waveforms were assessed using SphygmoCor software. As compared to baseline, pulse wave transit time decreased significantly for all four interventions indicating that central arterial stiffness increased. During fatiguing handgrip there was a fall in the ratio of peripheral to central pulse pressure from 1.69+/-0.02 at baseline to 1.56+/-0.05 (P<0.05). In the knee extensor protocol a non-significant trend for the opposite effect was noted. The augmentation index increased significantly during the arithmetic, short static and fatiguing handgrip protocols, whereas there was no change in the knee extensor protocol. We conclude that (1) during all types of acute stress tested in this study (including dynamic exercise) estimated central stiffness increased, (2) during static exercise the workload posed on the left ventricle (expressed as change in central pulse pressure) is relatively higher than that posed during dynamic exercise (given the same pulse pressure change in the periphery). PMID:18273040

  14. Acute Sheehan's syndrome presenting as central diabetes insipidus

    PubMed Central

    Robalo, Raquel; Pedroso, Célia; Agapito, Ana; Borges, Augusta

    2012-01-01

    Sheehan's syndrome occurs as a result of ischaemic pituitary necrosis due to severe postpartum haemorrhage. Improvements in obstetrical care have significantly reduced its incidence in developed countries, but postpartum pituitary infarction remains a common cause of hypopituitarism in developing countries. We report a case of severe postpartum haemorrhage followed by headache, central diabetes insipidus and failure to lactate, which prompted us to investigate and identify both anterior and posterior pituitary deficiency compatible with Sheehan's syndrome. A timely diagnosis allowed us to implement an adequate treatment and follow-up plan, which are known to improve clinical status and patient outcome. PMID:23131607

  15. The visual system of a palaeognathous bird: visual field, retinal topography and retino-central connections in the Chilean tinamou (Nothoprocta perdicaria).

    PubMed

    Krabichler, Quirin; Vega-Zuniga, Tomas; Morales, Cristian; Luksch, Harald; Marín, Gonzalo J

    2015-02-01

    Most systematic studies of the avian visual system have focused on Neognathous species, leaving virtually unexplored the Palaeognathae, comprised of the flightless ratites and the South American tinamous. We investigated the visual field, the retinal topography, and the pattern of retinal and centrifugal projections in the Chilean tinamou, a small Palaeognath of the family Tinamidae. The tinamou has a panoramic visual field with a small frontal binocular overlap of 20°. The retina possesses three distinct topographic specializations: a horizontal visual streak, a dorsotemporal area, and an area centralis with a shallow fovea. The maximum ganglion cell density is 61,900/ mm(2) , comparable to Falconiformes. This would provide a maximal visual acuity of 14.0 cycles/degree, in spite of relatively small eyes. The central retinal projections generally conform to the characteristic arrangement observed in Neognathae, with well-differentiated contralateral targets and very few ipsilateral fibers. The centrifugal visual system is composed of a considerable number of multipolar centrifugal neurons, resembling the "ectopic" neurons described in Neognathae. They form a diffuse nuclear structure, which may correspond to the ancestral condition shared with other sauropsids. A notable feature is the presence of terminals in deep tectal layers 11-13. These fibers may represent either a novel retinotectal pathway or collateral branches from centrifugal neurons projecting to the retina. Both types of connections have been described in chicken embryos. Our results widen the basis for comparative studies of the vertebrate visual system, stressing the conserved character of the visual projections' pattern within the avian clade. PMID:25224833

  16. Comparison of anti-vascular endothelial growth factors, laser treatments and a combination of the both for treatment of central retinal vein occlusion

    PubMed Central

    Pikkel, Yoav Y.; Sharabi-Nov, Adi; Beiran, Itzchak; Pikkel, Joseph

    2016-01-01

    AIM To compare changes in visual acuity and macular edema in patients with central retinal vein occlusion (CRVO) treated with intravitreal injections of bevacizumab, macular grid photocoagulation combined with pan retinal photocoagulation (PRP), or both (bevacizumab+grid+PRP). METHODS Our study is a retrospective cohort clinical study that examined patients that suffered from ischemic CRVO with macular edema. Study inclusion criteria were ischemic CRVO with macula edema and the availability of complete medical records for at least 12mo after treatment. Excluded were patients with diabetes or any other retinal disease. We reviewed the medical records of patients treated in one ophthalmology department-comparing changes in visual acuity and macular edema in patients treated with intravitreal injections of bevacizumab vs those that were treated with macular grid photocoagulation and PRP or both. The main outcome measures were the differences in best corrected visual acuity (BCVA) and in macular thickness, as assessed by optical coherence tomography, between the enrollment and the final follow up visits. RESULTS Sixty-five patients met inclusion criteria. There were no statistically significant differences among the three groups in the mean changes in macular thickness as measured by ocular coherence tomography (131.5±41.2, 108.6±29.2, and 121.1±121.1, P=0.110), or in visual acuity (0.128±0.077, 0.088±0.057, and 0.095±0.065), for intravitreal injections, macular grid photocoagulation+PRP and a combination of the treatments, respectively, P=0.111. The proportions of patients with macular edema after treatment were: 26.1%, 28.6%, and 14.3%, respectively, P=0.499. CONCLUSION Similar benefit was observed for intravitreal injections, laser photocoagulation, or a combined regimen in the treatment of CRVO. A non-statistically significant trend for reduction in macular edema was observed following combined treatment. PMID:27158615

  17. Driving with Central Visual Field Loss II: How Scotomas above or below the Preferred Retinal Locus (PRL) Affect Hazard Detection in a Driving Simulator

    PubMed Central

    Bowers, Alex R.; Goldstein, Robert; Peli, Eli

    2015-01-01

    We determined whether binocular central scotomas above or below the preferred retinal locus affect detection of hazards (pedestrians) approaching from the side. Seven participants with central field loss (CFL), and seven age-and sex-matched controls with normal vision (NV), each completed two sessions of 5 test drives (each approximately 10 minutes long) in a driving simulator. Participants pressed the horn when detecting pedestrians that appeared at one of four eccentricities (-14°, -4°, left, 4°, or 14°, right, relative to car heading). Pedestrians walked or ran towards the travel lane on a collision course with the participant’s vehicle, thus remaining in the same area of the visual field, assuming participant's steady forward gaze down the travel lane. Detection rates were nearly 100% for all participants. CFL participant reaction times were longer (median 2.27s, 95% CI 2.13 to 2.47) than NVs (median 1.17s, 95%CI 1.10 to 2.13; difference p<0.01), and CFL participants would have been unable to stop for 21% of pedestrians, compared with 3% for NV, p<0.001. Although the scotomas were not expected to obscure pedestrian hazards, gaze tracking revealed that scotomas did sometimes interfere with detection; late reactions usually occurred when pedestrians were entirely or partially obscured by the scotoma (time obscured correlated with reaction times, r = 0.57, p<0.001). We previously showed that scotomas lateral to the preferred retinal locus delay reaction times to a greater extent; however, taken together, the results of our studies suggest that any binocular CFL might negatively impact timely hazard detection while driving and should be a consideration when evaluating vision for driving. PMID:26332315

  18. Color Doppler imaging of retinal diseases.

    PubMed

    Dimitrova, Galina; Kato, Satoshi

    2010-01-01

    Color Doppler imaging (CDI) is a widely used method for evaluating ocular circulation that has been used in a number of studies on retinal diseases. CDI assesses blood velocity parameters by using ultrasound waves. In ophthalmology, these assessments are mainly performed on the retrobulbar blood vessels: the ophthalmic, the central retinal, and the short posterior ciliary arteries. In this review, we discuss CDI use for the assessment of retinal diseases classified into the following: vascular diseases, degenerations, dystrophies, and detachment. The retinal vascular diseases that have been investigated by CDI include diabetic retinopathy, retinal vein occlusions, retinal artery occlusions, ocular ischemic conditions, and retinopathy of prematurity. Degenerations and dystrophies included in this review are age-related macular degeneration, myopia, and retinitis pigmentosa. CDI has been used for the differential diagnosis of retinal detachment, as well as the evaluation of retrobulbar circulation in this condition. CDI is valuable for research and is a potentially useful diagnostic tool in the clinical setting. PMID:20385332

  19. Infectious Etiologies of Acute Febrile Illness among Patients Seeking Health Care in South-Central Cambodia

    PubMed Central

    Kasper, Matthew R.; Blair, Patrick J.; Touch, Sok; Sokhal, Buth; Yasuda, Chadwick Y.; Williams, Maya; Richards, Allen L.; Burgess, Timothy H.; Wierzba, Thomas F.; Putnam, Shannon D.

    2012-01-01

    The agents of human febrile illness can vary by region and country suggesting that diagnosis, treatment, and control programs need to be based on a methodical evaluation of area-specific etiologies. From December 2006 to December 2009, 9,997 individuals presenting with acute febrile illness at nine health care clinics in south-central Cambodia were enrolled in a study to elucidate the etiologies. Upon enrollment, respiratory specimens, whole blood, and serum were collected. Testing was performed for viral, bacterial, and parasitic pathogens. Etiologies were identified in 38.0% of patients. Influenza was the most frequent pathogen, followed by dengue, malaria, and bacterial pathogens isolated from blood culture. In addition, 3.5% of enrolled patients were infected with more than one pathogen. Our data provide the first systematic assessment of the etiologies of acute febrile illness in south-central Cambodia. Data from syndromic-based surveillance studies can help guide public health responses in developing nations. PMID:22302857

  20. Central retinal vein occlusion caused by hyperviscosity syndrome in a young patient with Sjögren's syndrome and MALT lymphoma.

    PubMed

    Yoshida, Atsushi; Watanabe, Meri; Ohmine, Ken; Kawashima, Hidetoshi

    2015-06-01

    We report in this article central retinal vein occlusion (CRVO) caused by hyperviscosity syndrome (HVS) in a young patient with mucosa-associated lymphoid tissue (MALT) lymphoma and Sjögren's syndrome (SjS). A 32-year-old female was referred to our hospital from a local ophthalmologist. Fundoscopic examination and fluorescein angiogram revealed she had a serous retinal detachment in the right eye, together with CRVO (nonischemic type) in both eyes. Systemic examinations revealed hyperglobulinemia, increased blood viscosity, increased antinuclear antibody, increased rheumatoid arthritis particle aggregation, and increased anti-SS-A antibody. Together with a decreased salivary gland secretory function, she was eventually diagnosed as suffering from SjS. Moreover, a large cystic mass was found in the anterior mediastinum on the chest X-ray. Fine needle biopsy soon revealed she had MALT lymphoma. After eight courses of the administration of rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP), most laboratory values were normalized, including blood viscosity. Cystic mass in the anterior mediastinum decreased, and the conditions of CRVO in both eyes had much improved. Decreased best-corrected visual acuity (BCVA) in the right eye was fully restored by sixth month. Not only MALT lymphoma, but also SjS can cause secondary hyperglobulinemia. Indeed, immunoelectrophoresis-serum test showed a polyclonal pattern of hyperglobulinemia. Therefore, SjS was thought to be the primary reason of hyperglobulinemia in this patient, which induced HVS, eventually causing CRVO. R-CVP therapy was effective for not only MALT lymphoma but also SjS accompanied with HVS. Consequently, R-CVP therapy led to the improvement of CRVO. PMID:25711376

  1. Next-generation sequencing of ABCA4: High frequency of complex alleles and novel mutations in patients with retinal dystrophies from Central Europe.

    PubMed

    Ścieżyńska, Aneta; Oziębło, Dominika; Ambroziak, Anna M; Korwin, Magdalena; Szulborski, Kamil; Krawczyński, Maciej; Stawiński, Piotr; Szaflik, Jerzy; Szaflik, Jacek P; Płoski, Rafał; Ołdak, Monika

    2016-04-01

    Variation in the ABCA4 locus has emerged as the most prevalent cause of monogenic retinal diseases. The study aimed to discover causative ABCA4 mutations in a large but not previously investigated cohort with ABCA4-related diseases originating from Central Europe and to refine the genetic relevance of all identified variants based on population evidence. Comprehensive clinical studies were performed to identify patients with Stargardt disease (STGD, n = 76) and cone-rod dystrophy (CRD, n = 16). Next-generation sequencing targeting ABCA4 was applied for a widespread screening of the gene. The results were analyzed in the context of exome data from a corresponding population (n = 594) and other large genomic databases. Our data disprove the pathogenic status of p.V552I and provide more evidence against a causal role of four further ABCA4 variants as drivers of the phenotype under a recessive paradigm. The study identifies 12 novel potentially pathogenic mutations (four of them recurrent) and a novel complex allele p.[(R152*; V2050L)]. In one third (31/92) of our cohort we detected the p.[(L541P; A1038V)] complex allele, which represents an unusually high level of genetic homogeneity for ABCA4-related diseases. Causative ABCA4 mutations account for 79% of STGD and 31% of CRD cases. A combination of p.[(L541P; A1038V)] and/or a truncating ABCA4 mutation always resulted in an early disease onset. Identification of ABCA4 retinopathies provides a specific molecular diagnosis and justifies a prompt introduction of simple precautions that may slow disease progression. The comprehensive, population-specific study expands our knowledge on the genetic landscape of retinal diseases. PMID:26593885

  2. Effect of an acute increase in central blood volume on cerebral hemodynamics.

    PubMed

    Ogoh, Shigehiko; Hirasawa, Ai; Raven, Peter B; Rebuffat, Thomas; Denise, Pierre; Lericollais, Romain; Sugawara, Jun; Normand, Hervé

    2015-10-15

    Systemic blood distribution is an important factor involved in regulating cerebral blood flow (CBF). However, the effect of an acute change in central blood volume (CBV) on CBF regulation remains unclear. To address our question, we sought to examine the CBF and systemic hemodynamic responses to microgravity during parabolic flight. Twelve healthy subjects were seated upright and exposed to microgravity during parabolic flight. During the brief periods of microgravity, mean arterial pressure was decreased (-26 ± 1%, P < 0.001), despite an increase in cardiac output (+21 ± 6%, P < 0.001). During microgravity, central arterial pulse pressure and estimated carotid sinus pressure increased rapidly. In addition, this increase in central arterial pulse pressure was associated with an arterial baroreflex-mediated decrease in heart rate (r = -0.888, P < 0.0001) and an increase in total vascular conductance (r = 0.711, P < 0.001). The middle cerebral artery mean blood velocity (MCA Vmean) remained unchanged throughout parabolic flight (P = 0.30). During microgravity the contribution of cardiac output to MCA Vmean was gradually reduced (P < 0.05), and its contribution was negatively correlated with an increase in total vascular conductance (r = -0.683, P < 0.0001). These findings suggest that the acute loading of the arterial and cardiopulmonary baroreceptors by increases in CBV during microgravity results in acute and marked systemic vasodilation. Furthermore, we conclude that this marked systemic vasodilation decreases the contribution of cardiac output to CBF. These findings suggest that the arterial and cardiopulmonary baroreflex-mediated peripheral vasodilation along with dynamic cerebral autoregulation counteracts a cerebral overperfusion, which otherwise would occur during acute increases in CBV. PMID:26310936

  3. Retinal Prosthesis

    PubMed Central

    Weiland, James D.; Humayun, Mark S.

    2015-01-01

    Retinal prosthesis have been translated from the laboratory to the clinical over the past two decades. Currently, two devices have regulatory approval for the treatment of retinitis pigmentosa. These devices provide partial sight restoration and patients use this improved vision in their everyday lives. Improved mobility and object detection are some of the more notable findings from the clinical trials. However, significant vision restoration will require both better technology and improved understanding of the interaction between electrical stimulation and the retina. This paper reviews the recent clinical trials, highlights technology breakthroughs that will contribute to next generation of retinal prostheses. PMID:24710817

  4. Foveomacular retinitis.

    PubMed Central

    Kuming, B S

    1986-01-01

    A group of patients is described who developed the clinical features of foveomacular retinitis. No causative factors were isolated, and all patients strongly denied any type of sun gazing. It is possible that there is a group of patients who have the features of foveomacular retinitis but have not had any direct exposure to the sun. These patients would then constitute a primary type of foveomacular retinitis, as opposed to a secondary type which has a known cause and is synonymous with solar retinopathy. Images PMID:3790482

  5. The role of the immune system in central nervous system plasticity after acute injury

    PubMed Central

    Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano

    2014-01-01

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalks between the injured brain and the immune system. In the acute phase, the damaged central nervous system (CNS) activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, which would ultimately bring the inflammatory reaction to a close. In the chronic phase, a sustained immune activation is described in many CNS disorders, and the degree of this prolonged response has variable effects on the spontaneous brain regenerative processes. The challenge for treating acute CNS damages is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Here we have reviewed the available information about the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of recovery after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that ultimately are associated to intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. PMID:24785677

  6. Functional biomarkers for the acute effects of alcohol on the central nervous system in healthy volunteers

    PubMed Central

    Zoethout, Remco W M; Delgado, Wilson L; Ippel, Annelies E; Dahan, Albert; van Gerven, Joop M A

    2011-01-01

    The central nervous system (CNS) effects of acute alcohol administration have been frequently assessed. Such studies often use a wide range of methods to study each of these effects. Unfortunately, the sensitivity of these tests has not completely been ascertained. A literature search was performed to recognize the most useful tests (or biomarkers) for identifying the acute CNS effects of alcohol in healthy volunteers. All tests were grouped in clusters and functional domains. Afterwards, the effect of alcohol administration on these tests was scored as improvement, impairment or as no effect. Furthermore, dose–response relationships were established. A total number of 218 studies, describing 342 different tests (or test variants) were evaluated. Alcohol affected a wide range of CNS domains. Divided attention, focused attention, visuo-motor control and scales of feeling high and of subjective drug effects were identified as the most sensitive functional biomarkers for the acute CNS effects of alcohol. The large number of CNS tests that are used to determine the effects of alcohol interferes with the identification of the most sensitive ones and of drug–response relationships. Our results may be helpful in selecting rational biomarkers for studies investigating the acute CNS effects of alcohol or for future alcohol- interaction studies. PMID:21284693

  7. A Validated System for Centralized Grading of Retinopathy of Prematurity: Telemedicine Approaches to Evaluating Acute Phase ROP (e-ROP) Study

    PubMed Central

    Daniel, Ebenezer; Quinn, Graham E.; Hildebrand, P. Lloyd; Ells, Anna; Hubbard, Baker; Capone, Antonio; Martin, Revell W.; Ostroff, Candace P.; Smith, Eli; Pistilli, Maxwell; Ying, Gui-Shuang

    2016-01-01

    Importance Measurable competence derived from comprehensive and advanced training in grading digital images is critical in studies using a Reading Center to evaluate retinal fundus images from infants at risk for Retinopathy of Prematurity (ROP). Details of certification for non-physician Trained Readers (TR) have not yet been described. Objective Describe a centralized system for grading ROP digital images by TRs in the “Telemedicine Approaches to evaluating acute-phase Retinopathy of Prematurity (e-ROP) Study”. Design Multi-center observational cohort study. Setting TRs were trained by experienced ROP specialists and certified to detect ROP morphology in digital retinal images under supervision of an ophthalmologist Reading Center Director (RCD). An ROP Reading Center was developed with standard hardware, secure Internet access and customized image viewing software with an electronic grading form. A detailed protocol for grading was developed. Based on results of TR gradings, a computerized algorithm determined whether Referral-Warranted ROP (RW-ROP, defined as presence of plus disease, zone I ROP, and stage 3 or worse ROP) was present. Independent double grading was done by the TRs with adjudication of discrepant fields performed by the RCD. Participants Infants with birth weights <1251g. Interventions/Exposures Digital retinal images Main Outcome Measure(s) Intra- and inter-grader variability, and monitoring for temporal drift. Results Four TRs underwent rigorous training and certification. 5,520 image sets were double graded with 25% requiring adjudication for at least one component of RW-ROP. The weighted kappas for inter-grader agreement (N= 80 image sets) were 0.72 (0.52 – 0.93) for RW-ROP, 0.57(95% CI: 0.37 – 0.77) for plus disease, 0.43 (0.24 – 0.63) for zone I ROP and 0.67(0.47 – 0.88) for Stage 3 or worse ROP. The weighted kappa for grade re-grade agreement were 0.77(0.57 – 0.97) for RW- ROP, 0.87(0.67 – 1.00) for plus disease, 0

  8. Bird eyes distinguish summer from winter: Retinal response to acute photoperiod change in the night-migratory redheaded bunting.

    PubMed

    Majumdar, Gaurav; Yadav, Garima; Rani, Sangeeta; Kumar, Vinod

    2015-10-01

    Eyes are the part of the circadian timekeeping system but not involved in the photoperiod regulated seasonal physiology in songbirds. Here, two experiments tested whether eyes detect and respond to seasonal change in the photoperiod environment, by examining gene and protein expressions in the retinas of redheaded buntings exposed to a single long day (LD, 16L:8D), with controls on short days (SD, 8L:16D). In the first experiment, mRNA expression of genes implicated in the light perception (opsins, rhodopsin, neuropsin, melanopsin, peropsin) and photoperiod induction (eya3, tsh-β, dio2, dio3) was measured at hours 15 and 19 (hour 0 = light on) on the first long day. There was a significant increase in the eya3, tsh-β and dio2 mRNA expression, albeit with a temporal difference, and decrease in the neuropsin mRNA expression in buntings on the first long day. There was no change in the dio3, rhodopsin, melanopsin and peropsin mRNA expressions on exposure to long days. The second experiment immunohistochemically examined the eya3, tsh-β and rhodopsin peptide expressions. eya3 was expressed in both light conditions, but with a significant higher levels in the retinal photoreceptor layer (PRL) under LD, as compared to SD. Similarly, tsh-β was expressed in the PRL of LD retinas only. Rhodopsin levels were not significantly different between SD and LD conditions, however. These results for the first time show photoperiod-dependent molecular switches in the bunting retina, similar to the well documented thyroid hormone response genes based molecular cascades in the avian hypothalamus. PMID:26219493

  9. Retinal Detachment

    MedlinePlus

    ... immediately. Treatment How is retinal detachment treated? Small holes and tears are treated with laser surgery or ... laser surgery tiny burns are made around the hole to “weld” the retina back into place. Cryopexy ...

  10. Acute and prolonged complement activation in the central nervous system during herpes simplex encephalitis.

    PubMed

    Eriksson, Charlotta E; Studahl, Marie; Bergström, Tomas

    2016-06-15

    Herpes simplex encephalitis (HSE) is characterized by a pronounced inflammatory activity in the central nervous system (CNS). Here, we investigated the acute and prolonged complement system activity in HSE patients, by using enzyme-linked immunosorbent assays (ELISAs) for numerous complement components (C). We found increased cerebrospinal fluid concentrations of C3a, C3b, C5 and C5a in HSE patients compared with healthy controls. C3a and C5a concentrations remained increased also compared with patient controls. Our results conclude that the complement system is activated in CNS during HSE in the acute phase, and interestingly also in later stages supporting previous reports of prolonged inflammation. PMID:27235358

  11. A Meta-Analysis of Anti-Vascular Endothelial Growth Factor Remedy for Macular Edema Secondary to Central Retinal Vein Occlusion

    PubMed Central

    Huang, Peirong; Niu, Wenquan; Ni, Zhentian; Wang, Renzuo; Sun, Xiaodong

    2013-01-01

    Background Central retinal vein occlusion (CRVO) associates with severe vision outcome and no proven beneficial treatment. Our meta-analysis intended to appraise the efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) agents in macular edema (ME) following CRVO. Methods Data were collected and analyzed by Review Manager 5.2.1. We employed a random-effects model to eliminate between-study heterogeneity. Nfs (called fail-safe number) was calculated to evaluate the publication bias. Results We included 5 trials consisting 323 cases and 281 controls. Primary outcomes showed that overall comparison of anti-VEGF agents with placebo control yielded a 374% and 136% increased tendency for a gain of 15 letters or more on Early Treatment Diabetic Retinopathy Study (ETDRS) chart (95% confidence interval [95% CI]: 2.43–9.23; P<0.00001; I2 = 59%, 95% CI: 1.60–3.49; P<0.0001; I2 = 0%, respectively) at 6 and 12 months. Secondary outcomes showed that a 90% and 77% decreased risk at 6 and 12 months for a loss of 15 letters or more. The overall mean difference showed a statistically significance in best-corrected visual acuity (BCVA) on each time point. However, changes of central retinal thickness (CRT) lost significance at 12 months after 6-month as-needed treatment. The incidence of adverse events (AEs) had no statistical difference between anti-VEGF and placebo groups. Subgroup analyses indicated that patients receiving Aflibercept got the highest tendency to gain 15 letters or more (OR = 9.78; 95% CI: 4.43–21.56; P<0.00001). Age controlled analysis suggested a weaken tendency of BCVA improvement in age over 50 (MD = 12.26; 95% CI: 7.55–16.98; P<0.00001). Subgroup analysis by clinical classification showed a strengthen difference of BCVA changes at 6 months in ischemic type (MD = 19.65 letters, 95% CI: 13.15 to 26.14 letters, P<0.00001). Conclusions Our results showed that anti-VEGF agents were superior to placebo in CRVO

  12. Ocular blood flow levels and visual prognosis in a patient with nonischemic type central retinal vein occlusion

    PubMed Central

    Maeda, Kimihito; Ishikawa, Futoshi; Ohguro, Hiroshi

    2009-01-01

    We look at the case of a 39-year-old female patient suffering from a sudden decrease in her left visual acuity (0.08). Her macular edema was examined using optical coherence tomography, and her optic disc blood flow was examined with laser speckle flowgraphy (LSFG). Additionally, the degree of seriousness of the central vein occlusion was evaluated through fluorescein angiography (FA). Ocular fundus findings revealed central vein occlusion associated with macular edema, and FA determined her disease type as a nonischemic-central vein occlusion. Daily doses of 100 mg of aspirin were administered orally to the patient. Upon administration, her ocular blood flow almost immediately increased. In this study, we demonstrate the potential of LSFG as a means to investigate ocular blood flow. PMID:19750123

  13. Ocular blood flow levels and visual prognosis in a patient with nonischemic type central retinal vein occlusion.

    PubMed

    Maeda, Kimihito; Ishikawa, Futoshi; Ohguro, Hiroshi

    2009-01-01

    We look at the case of a 39-year-old female patient suffering from a sudden decrease in her left visual acuity (0.08). Her macular edema was examined using optical coherence tomography, and her optic disc blood flow was examined with laser speckle flowgraphy (LSFG). Additionally, the degree of seriousness of the central vein occlusion was evaluated through fluorescein angiography (FA). Ocular fundus findings revealed central vein occlusion associated with macular edema, and FA determined her disease type as a nonischemic-central vein occlusion. Daily doses of 100 mg of aspirin were administered orally to the patient. Upon administration, her ocular blood flow almost immediately increased. In this study, we demonstrate the potential of LSFG as a means to investigate ocular blood flow. PMID:19750123

  14. Retinal Stimulation on Rabbit Using Complementary Metal Oxide Semiconductor Based Multichip Flexible Stimulator toward Retinal Prosthesis

    NASA Astrophysics Data System (ADS)

    Tokuda, Takashi; Asano, Ryosuke; Sugitani, Sachie; Taniyama, Mari; Terasawa, Yasuo; Nunoshita, Masahiro; Nakauchi, Kazuaki; Fujikado, Takashi; Tano, Yasuo; Ohta, Jun

    2008-04-01

    The Functionality of a complementary metal oxide semiconductor (CMOS) LSI-based, multichip flexible retinal stimulator was demonstrated in retinal stimulation experiments on rabbits. A 1×4-configured multichip stimulator was fabricated for application to experiments on animals. An experimental procedure including surgical operations was developed, and retinal stimulation was performed with the fabricated multichip stimulator. Neural responses on the visual cortex were successfully evoked by the fabricated stimulator. The stimulator is confirmed to be applicable to acute animal experiments.

  15. Current perspectives of herpesviral retinitis and choroiditis.

    PubMed

    Madhavan, H N; Priya, K; Biswas, J

    2004-10-01

    Vision-threatening viral retinitis are primarily caused by members of the herpesvirus family. The biology and molecular characterization of herpesviruses, clinical presentations of retinopathies, pathology and pathogenesis including the host responses, epidemiology and the laboratory methods of aetiological diagnosis of these diseases are described. Clinical syndromes are acute retinal necrosis (ARN), progressive outer retinal necrosis (PORN), cytomegalovirus (CMV) retinitis, multifocal choroiditis and serpiginous choroiditis besides other viral retinopathies. Herpes simplex virus (HSV) retinitis is more common in immunocompetent persons while varicella zoster virus (VZV) affects both immunocompetent and immunosuppressed patients equally. CMV retinitis is most common among patients with AIDS. The currently employed laboratory methods of antigen detection, virus isolation and antibody detection by enzyme linked immuno-sorbent assay (ELISA) have low sensitivity. Polymerase chain reaction (PCR) has increased the value of diagnosis due to its high clinical sensitivity and absolute specificity in detection of herpesviruses in intraocular specimens. PMID:16295367

  16. Retinal abnormalities in β-thalassemia major.

    PubMed

    Bhoiwala, Devang L; Dunaief, Joshua L

    2016-01-01

    Patients with beta (β)-thalassemia (β-TM: β-thalassemia major, β-TI: β-thalassemia intermedia) have a variety of complications that may affect all organs, including the eye. Ocular abnormalities include retinal pigment epithelial degeneration, angioid streaks, venous tortuosity, night blindness, visual field defects, decreased visual acuity, color vision abnormalities, and acute visual loss. Patients with β-thalassemia major are transfusion dependent and require iron chelation therapy to survive. Retinal degeneration may result from either retinal iron accumulation from transfusion-induced iron overload or retinal toxicity induced by iron chelation therapy. Some who were never treated with iron chelation therapy exhibited retinopathy, and others receiving iron chelation therapy had chelator-induced retinopathy. We will focus on retinal abnormalities present in individuals with β-thalassemia major viewed in light of new findings on the mechanisms and manifestations of retinal iron toxicity. PMID:26325202

  17. Fellow Eye Changes in Patients with Nonischemic Central Retinal Vein Occlusion: Assessment of Perfused Foveal Microvascular Density and Identification of Nonperfused Capillaries

    PubMed Central

    Pinhas, Alexander; Dubow, Michael; Shah, Nishit; Cheang, Eric; Liu, Chun L.; Razeen, Moataz; Gan, Alexander; Weitz, Rishard; Sulai, Yusufu N.; Chui, Toco Y.; Dubra, Alfredo; Rosen, Richard B.

    2016-01-01

    Purpose Eyes fellow to nonischemic central retinal vein occlusion (CRVO) were examined for abnormalities, which might explain their increased risk for future occlusion, using adaptive optics scanning light ophthalmoscope fluorescein angiography. Methods Adaptive optics scanning light ophthalmoscope fluorescein angiography foveal microvascular densities were calculated. Nonperfused capillaries adjacent to the foveal avascular zone were identified. Spectral domain optical coherence tomography, ultrawide field fluorescein angiographies, and microperimetry were also performed. Results Ten fellow eyes of nine nonischemic CRVO and 1 nonischemic hemi-CRVO subjects and four affected eyes of three nonischemic CRVO and one nonischemic hemi-CRVO subjects were imaged. Ninety percent of fellow eyes and 100% of affected eyes demonstrated at least 1 nonperfused capillary compared with 31% of healthy eyes. Fellow eye microvascular density (35 ± 3.6 mm−1) was significantly higher than that of affected eyes (25 ± 5.2 mm−1) and significantly lower than that of healthy eyes (42 ± 4.2 mm−1). Compared with healthy controls, spectral domain optical coherence tomography thicknesses showed no significant difference, whereas microperimetry and 2/9 ultrawide field fluorescein angiography revealed abnormalities in fellow eyes. Conclusion Fellow eye changes detectable on adaptive optics scanning light ophthalmoscope fluorescein angiography reflect subclinical pathology difficult to detect using conventional imaging technologies. These changes may help elucidate the pathogenesis of nonischemic CRVO and help identify eyes at increased risk of future occlusion. PMID:25932560

  18. The central role of hypothalamic inflammation in the acute illness response and cachexia.

    PubMed

    Burfeind, Kevin G; Michaelis, Katherine A; Marks, Daniel L

    2016-06-01

    When challenged with a variety of inflammatory threats, multiple systems across the body undergo physiological responses to promote defense and survival. The constellation of fever, anorexia, and fatigue is known as the acute illness response, and represents an adaptive behavioral and physiological reaction to stimuli such as infection. On the other end of the spectrum, cachexia is a deadly and clinically challenging syndrome involving anorexia, fatigue, and muscle wasting. Both of these processes are governed by inflammatory mediators including cytokines, chemokines, and immune cells. Though the effects of cachexia can be partially explained by direct effects of disease processes on wasting tissues, a growing body of evidence shows the central nervous system (CNS) also plays an essential mechanistic role in cachexia. In the context of inflammatory stress, the hypothalamus integrates signals from peripheral systems, which it translates into neuroendocrine perturbations, altered neuronal signaling, and global metabolic derangements. Therefore, we will discuss how hypothalamic inflammation is an essential driver of both the acute illness response and cachexia, and why this organ is uniquely equipped to generate and maintain chronic inflammation. First, we will focus on the role of the hypothalamus in acute responses to dietary and infectious stimuli. Next, we will discuss the role of cytokines in driving homeostatic disequilibrium, resulting in muscle wasting, anorexia, and weight loss. Finally, we will address mechanisms and mediators of chronic hypothalamic inflammation, including endothelial cells, chemokines, and peripheral leukocytes. PMID:26541482

  19. Time Profile of Viral DNA in Aqueous Humor Samples of Patients Treated for Varicella-Zoster Virus Acute Retinal Necrosis by Use of Quantitative Real-Time PCR

    PubMed Central

    Bernheim, D.; Germi, R.; Labetoulle, M.; Romanet, J. P.; Morand, P.

    2013-01-01

    The objective of this study was to evaluate the kinetics of varicella-zoster virus (VZV) loads using quantitative PCR (qPCR) in patients treated for acute retinal necrosis (ARN). Six patients (52 ± 13 years old) with ARN syndrome were consecutively studied. Aqueous humor (AH) was sampled from both eyes of all patients for qPCR evaluation. The patients were treated with intravenous acyclovir and intravitreal injections of antiviral drugs. The mean follow-up time was 17.6 ± 16.4 months. Main outcome measures were the numbers of viral genome copies in the AH, assessed using real-time qPCR with hydrolysis probe technology with a threshold of detection of 200 copies/ml. Two main portions of the viral load curves were observed for each patient: a plateau phase (27.8 ± 24.9 days) and a decrease in the number of viral genome copies. The mean baseline viral load was 3.4 × 107 ± 4.45 × 107 copies/ml (6 × 106 to 1.2 × 108 copies/ml). The viral load decreased according to a logarithmic model, with a 50% reduction obtained in 3 ± 0.7 days. There was a significant viral load (>102 copies/ml) at 50 days after the onset of treatment, despite antiviral drugs. qPCR use demonstrated reproducible VZV DNA kinetics with a two-phase evolution: a plateau followed by a logarithmic decrease. These data suggest that high-dosage antiviral therapy administered for the conventional 10-day duration is insufficient for most patients. This series of patients responded with a similar decrease in viral load once treatment was initiated, and the data from these patients may be used to predict the responses of future patients. PMID:23637296

  20. Time profile of viral DNA in aqueous humor samples of patients treated for varicella-zoster virus acute retinal necrosis by use of quantitative real-time PCR.

    PubMed

    Bernheim, D; Germi, R; Labetoulle, M; Romanet, J P; Morand, P; Chiquet, C

    2013-07-01

    The objective of this study was to evaluate the kinetics of varicella-zoster virus (VZV) loads using quantitative PCR (qPCR) in patients treated for acute retinal necrosis (ARN). Six patients (52 ± 13 years old) with ARN syndrome were consecutively studied. Aqueous humor (AH) was sampled from both eyes of all patients for qPCR evaluation. The patients were treated with intravenous acyclovir and intravitreal injections of antiviral drugs. The mean follow-up time was 17.6 ± 16.4 months. Main outcome measures were the numbers of viral genome copies in the AH, assessed using real-time qPCR with hydrolysis probe technology with a threshold of detection of 200 copies/ml. Two main portions of the viral load curves were observed for each patient: a plateau phase (27.8 ± 24.9 days) and a decrease in the number of viral genome copies. The mean baseline viral load was 3.4 × 10(7) ± 4.45 × 10(7) copies/ml (6 × 10(6) to 1.2 × 10(8) copies/ml). The viral load decreased according to a logarithmic model, with a 50% reduction obtained in 3 ± 0.7 days. There was a significant viral load (>102 copies/ml) at 50 days after the onset of treatment, despite antiviral drugs. qPCR use demonstrated reproducible VZV DNA kinetics with a two-phase evolution: a plateau followed by a logarithmic decrease. These data suggest that high-dosage antiviral therapy administered for the conventional 10-day duration is insufficient for most patients. This series of patients responded with a similar decrease in viral load once treatment was initiated, and the data from these patients may be used to predict the responses of future patients. PMID:23637296

  1. Central nervous insulin administration does not potentiate the acute glucoregulatory impact of concurrent mild hyperinsulinemia.

    PubMed

    Ott, Volker; Lehnert, Hendrik; Staub, Josefine; Wönne, Kathrin; Born, Jan; Hallschmid, Manfred

    2015-03-01

    Experiments in rodents suggest that hypothalamic insulin signaling essentially contributes to the acute control of peripheral glucose homeostasis. Against this background, we investigated in healthy humans whether intranasal (IN) insulin, which is known to effectively reach the brain compartment, impacts systemic glucose metabolism. Twenty overnight-fasted healthy, normal-weight men were IN administered 210 and 420 international units [IU] (10 and 20 IU every 15 min) of the insulin analog aspart (ins-asp) and placebo, respectively, during experimental sessions lasting 6 h. The use of ins-asp rather than human insulin enabled us to disentangle exogenous and endogenous insulin kinetics. IN insulin dose-dependently decreased plasma glucose concentrations while reducing C-peptide and attenuating endogenous insulin levels. However, we also observed a slight dose-dependent permeation of ins-asp into the circulation. In control experiments mimicking the systemic but not the central nervous uptake of the IN 210 IU dose via intravenous infusion of ins-asp at a dose of 0.12 IU/kg/24 h (n = 10), we obtained essentially identical effects on fasting plasma glucose concentrations. This pattern indicates that sustained IN insulin administration to the human brain to enhance central nervous insulin signaling does not acutely alter systemic glucose homeostasis beyond effects accounted for by concurrent mild hyperinsulinemia. PMID:25277390

  2. Comparison of the effects of intravitreal bevacizumab and triamcinolone acetonide in the treatment of macular edema secondary to central retinal vein occlusion

    PubMed Central

    Demir, Mehmet; Dirim, Burcu; Acar, Zeynep; Sendul, Yekta; Oba, Ersin

    2014-01-01

    Aim: To compare the effects of intravitrealbevacizumab (IVB) and intravitreal triamcinolone acetonide (IVT) in the treatment of macular edema (ME) secondary to central retinal vein occlusion (CRVO). Materials and Methods: There were 20 patients treated with IVB (1.25 mg/0.05 mL) and 16 treated with IVT (4 mg/0.1 mL). The two groups were compared with regard to best-corrected visual acuity (BCVA), central macular thickness (CMT) on optical coherence tomography (OCT), slit-lamp biomicroscopy and fundus fluorescein angiography results, intraocular pressure (IOP), numbers of injections, and adverse events. Results: The mean follow-up times in the IVB and IVT groups were 17.45±8.1 months (range: 8–33 months) and 19.94±10.59 months (range: 6–40 months), respectively (P = 0.431). Visual acuity increased and CMT decreased significantly within both groups, but no differences were observed between the groups (P = 0.718). The percentages of patients with increased IOP and iatrogenic cataracts were significantly higher in the IVT group than in the IVB group. Conclusions: Treatment with IVB and IVT both resulted in significant improvement in visual acuity and a decrease in CMT in patients with ME secondary to non-ischemic CRVO, with no difference between the two treatments. The incidence of adverse events, however, was significantly greater in the IVT group than in the IVB group. IVB may be preferred over IVT for the treatment of ME in patients with non-ischemic CRVO. PMID:23571251

  3. Diurnal Variations in Intraocular Pressure, Central Corneal Thickness, and Macular and Retinal Nerve Fiber Layer Thickness in Diabetics and Normal Individuals

    PubMed Central

    Sharifipour, Farideh; Farrahi, Fereidoun; Moghaddasi, Alireza; Idani, Aida; Yaseri, Mehdi

    2016-01-01

    Purpose: To evaluate diurnal variations in intraocular pressure (IOP), central corneal thickness (CCT), and macular and retinal nerve fiber layer (RNFL) thickness in diabetic patients and normal individuals. Methods: This study included 11 diabetic patients with macular edema and 11 healthy individuals. IOP, CCT, and macular and RNFL thickness were measured every 3 hours on a single day between 9 AM and 6 PM. Diurnal variations in IOP, CCT, total macular volume (TMV), central macular thickness (CMT), average macular thickness (AMT), and RNFL thickness were measured. Results: None of the parameters showed a significant absolute or relative change over the course of the day. However, the following non-significant changes were observed. In the control group, all parameters demonstrated the highest values at 9 AM. The lowest IOP, TMV and AMT occurred at 12 PM; lowest CCT and RNFL at 6 PM; and the lowest CMT at 3 PM. Diabetic subjects had the highest values of RNFL, CMT and TMV at 9 AM, and that for IOP, CCT and AMT at 6 PM. The lowest RNFL and CMT values occurred at 6 PM; lowest IOP at 12 PM; and the lowest CCT, TMV and AMT were observed at 3 PM. In the diabetic group, TMV, CMT, AMT and CCT were significantly higher and RNFL was significantly lower than the control group at all time points (all P- values < 0.05). Conclusion: While there were slight decreases in IOP, RNFL thickness and CMT during the day, these changes were not significant between 9 AM and 6 PM and probably do not affect the interpretation of measurements. PMID:27195084

  4. Acetylation: A Lysine Modification with Neuroprotective Effects in Ischemic Retinal Degeneration

    PubMed Central

    Alsarraf, Oday; Fan, Jie; Dahrouj, Mohammad; Chou, C. James; Menick, Donald R.; Crosson, Craig E.

    2014-01-01

    Purpose Neuroretinal ischemic injury contributes to several degenerative diseases in the eye and the resulting pathogenic processes involving a series of necrotic and apoptotic events. This study investigates the time and extent of changes in acetylation, and whether this influences function and survival of neuroretinal cells following injury. Methods Studies evaluated the time course of changes in histone deacetylase (HDAC) activity, histone-H3 acetylation and caspase-3 activation levels as well as retinal morphology and function (electroretinography) following ischemia. In addition, the effect of two HDAC inhibitors, trichostatin-A and valproic acid were also investigated. Results In normal eyes, retinal ischemia produced a significant increase in HDAC activity within 2 hours that was followed by a corresponding significant decrease in protein acetylation by 4 hours. Activated caspase-3 levels were significantly elevated by 24 hours. Treatment with HDAC inhibitors blocked the early decrease in protein acetylation and activation of caspase-3. Retinal immunohistochemistry demonstrated that systemic administration of trichostatin-A or valproic acid, resulted in hyperacetylation of all retinal layers after systemic treatment. In addition, HDAC inhibitors provided a significant functional and structural neuroprtection at seven days following injury relative to vehicle-treated eyes. Conclusions These results provide evidence that increases in HDAC activity is an early event following retinal ischemia, and are accompanied by corresponding decreases in acetylation in advance of caspase-3 activation. In addition to preserving acetylation status, the administration of HDAC inhibitors suppressed caspase activation and provided structural and functional neuroprotection in model of ischemic retinal injury. Taken together these data provide evidence that decrease in retinal acetylation status is a central event in ischemic retinal injury, and the hyperacetylation induced by

  5. Acetylation: a lysine modification with neuroprotective effects in ischemic retinal degeneration.

    PubMed

    Alsarraf, Oday; Fan, Jie; Dahrouj, Mohammad; Chou, C James; Menick, Donald R; Crosson, Craig E

    2014-10-01

    Neuroretinal ischemic injury contributes to several degenerative diseases in the eye and the resulting pathogenic processes involving a series of necrotic and apoptotic events. This study investigates the time and extent of changes in acetylation, and whether this influences function and survival of neuroretinal cells following injury. Studies evaluated the time course of changes in histone deacetylase (HDAC) activity, histone-H3 acetylation and caspase-3 activation levels as well as retinal morphology and function (electroretinography) following ischemia. In addition, the effect of two HDAC inhibitors, trichostatin-A and valproic acid were also investigated. In normal eyes, retinal ischemia produced a significant increase in HDAC activity within 2 h that was followed by a corresponding significant decrease in protein acetylation by 4 h. Activated caspase-3 levels were significantly elevated by 24 h. Treatment with HDAC inhibitors blocked the early decrease in protein acetylation and activation of caspase-3. Retinal immunohistochemistry demonstrated that systemic administration of trichostatin-A or valproic acid, resulted in hyperacetylation of all retinal layers after systemic treatment. In addition, HDAC inhibitors provided a significant functional and structural neuroprotection at seven days following injury relative to vehicle-treated eyes. These results provide evidence that increases in HDAC activity is an early event following retinal ischemia, and are accompanied by corresponding decreases in acetylation in advance of caspase-3 activation. In addition to preserving acetylation status, the administration of HDAC inhibitors suppressed caspase activation and provided structural and functional neuroprotection in model of ischemic retinal injury. Taken together these data provide evidence that decrease in retinal acetylation status is a central event in ischemic retinal injury, and the hyperacetylation induced by HDAC inhibition can provide acute

  6. Retinal vascular changes are a marker for cerebral vascular diseases

    PubMed Central

    Moss, Heather E.

    2016-01-01

    The retinal circulation is a potential marker of cerebral vascular disease because it shares origin and drainage with the intracranial circulation and because it can be directly visualized using ophthalmoscopy. Cross sectional and cohort studies have demonstrated associations between chronic retinal and cerebral vascular disease, acute retinal and cerebral vascular disease and chronic retinal vascular disease and acute cerebral vascular disease. In particular, certain qualitative features of retinopathy, retinal artery occlusion and increased retinal vein caliber are associated with concurrent and future cerebrovascular events. These associations persist after accounting for confounding variables known to be disease-causing in both circulations, which supports the potential use of retinal vasculature findings to stratify individuals with regards to cerebral vascular disease risk. PMID:26008809

  7. Microsystems Technology for Retinal Implants

    NASA Astrophysics Data System (ADS)

    Weiland, James

    2005-03-01

    The retinal prosthesis is targeted to treat age-related macular degeneration, retinitis pigmentosa, and other outer retinal degenerations. Simulations of artificial vision have predicted that 600-1000 individual pixels will be needed if a retinal prosthesis is to restore function such as reading large print and face recognition. An implantable device with this many electrode contacts will require microsystems technology as part of its design. An implantable retinal prosthesis will consist of several subsystems including an electrode array and hermetic packaging. Microsystems and microtechnology approaches are being investigated as possible solutions for these design problems. Flexible polydimethylsiloxane (PDMS) substrate electrode arrays and silicon micromachined electrode arrays are under development. Inactive PDMS electrodes have been implanted in 3 dogs to assess mechanical biocompatibility. 3 dogs were followed for 6 months. The implanted was securely fastened to the retina with a single retinal tack. No post-operative complications were evident. The array remained within 100 microns of the retinal surface. Histological evaluation showed a well preserved retina underneath the electrode array. A silicon device with electrodes suspended on micromachined springs has been implanted in 4 dogs (2 acute implants, 2 chronic implants). The device, though large, could be inserted into the eye and positioned on the retina. Histological analysis of the retina from the spring electrode implants showed that spring mounted posts penetrated the retina, thus the device will be redesigned to reduce the strength of the springs. These initial implants will provide information for the designers to make the next generation silicon device. We conclude that microsystems technology has the potential to make possible a retinal prosthesis with 1000 individual contacts in close proximity to the retina.

  8. Retinal detachment

    MedlinePlus

    ... of the first symptoms of new flashes of light and floaters. ... diabetes. See your eye care specialist once a year. You may need more frequent visits if you have risk factors for retinal detachment. Be alert to symptoms of new flashes of light and floaters.

  9. A Randomized Trial Comparing the Efficacy and Safety of Intravitreal Triamcinolone With Observation to Treat Vision Loss Associated With Macular Edema Secondary to Central Retinal Vein Occlusion

    PubMed Central

    Ip, Michael S.; Scott, Ingrid U.; VanVeldhuisen, Paul C.; Oden, Neal L.; Blodi, Barbara A.; Fisher, Marian; Singerman, Lawrence J.; Tolentino, Michael; Chan, Clement K.; Gonzalez, Victor H.

    2009-01-01

    Objective: To compare the efficacy and safety of 1-mg and 4-mg doses of preservative-free intravitreal triamcinolone with observation for eyes with vision loss associated with macular edema secondary to perfused central retinal vein occlusion (CRVO). Methods: Multicenter, randomized, clinical trial of 271 participants. Main Outcome Measure: Gain in visual acuity letter score of 15 or more from baseline to month 12. Results: Seven percent, 27%, and 26% of participants achieved the primary outcome in the observation, 1-mg, and 4-mg groups, respectively. The odds of achieving the primary outcome were 5.0 times greater in the 1-mg group than the observation group (odds ratio [OR],5.0; 95% confidence interval [CI], 1.8-14.1; P=.001) and 5.0 times greater in 4-mg group than the observation group (OR,5.0; 95% CI, 1.8-14.4; P=.001); there was no difference identified between the 1-mg and 4-mg groups (OR, 1.0; 95% CI, 0.5-2.1; P=.97). The rates of elevated intraocular pressure and cataract were similar for the observation and 1-mg groups, but higher in the 4-mg group. Conclusions: Intravitreal triamcinolone is superior to observation for treating vision loss associated with macular edema secondary to CRVO in patients who have characteristics similar to those in the SCORE-CRVO trial. The 1-mg dose has a safety profile superior to that of the 4-mg dose. Application to Clinical Practice: Intravitreal triamcinolone in a 1-mg dose, following the retreatment criteria applied in the SCORE Study, should be considered for up to 1 year, and possibly 2 years, for patients with characteristics similar to those in the SCORE-CRVO trial. Trial Registration: clinicaltrials.gov Identifier: NCT00105027 PMID:19752419

  10. Intravitreal aflibercept (Eylea(®)): a review of its use in patients with macular oedema secondary to central retinal vein occlusion.

    PubMed

    Yang, Lily P H; McKeage, Kate

    2014-05-01

    Aflibercept is a fully human, recombinant fusion protein that acts as a soluble decoy receptor for vascular endothelial growth factor (VEGF) family members, including VEGF-A, VEGF-B and placental growth factor (P1GF), thereby inhibiting downstream signalling mediated by these ligands. Aflibercept binds all isoforms of VEGF-A with high affinity, and a markedly higher affinity than that of ranibizumab or bevacizumab. A formulation of aflibercept developed specifically for intravitreal injection (Eylea(®)) is approved for use in several countries for the treatment of patients with macular oedema secondary to central retinal vein occlusion (CRVO). In clinical trials (GALILEO and COPERNICUS) in patients with this condition, intravitreal aflibercept 2 mg every month improved best corrected visual acuity (BCVA), as measured by the proportion of study eyes with a gain of ≥15 Early Treatment Diabetic Retinopathy Study letters from baseline, significantly more than sham injections at week 24 (primary analysis). The significant improvements achieved with intravitreal aflibercept compared with sham in the first 6 months were maintained in the second 6 months with as-needed (prn) dosing and monthly monitoring. Continued prn dosing with a reduced monitoring frequency was associated with decreased improvements. More data are needed to confirm the optimal monitoring frequency for use with prn dosing, subsequent to initial monthly injections, in order to maintain long-term efficacy. Intravitreal aflibercept was generally well tolerated in clinical trials and there is little potential for systemic drug accumulation. Thus, intravitreal aflibercept is an effective and generally well tolerated agent that extends the options available for the treatment of macular oedema secondary to CRVO. PMID:24740170

  11. Do growth-stimulated retinal ganglion cell axons find their central targets after optic nerve injury? New insights by three-dimensional imaging of the visual pathway.

    PubMed

    Diekmann, Heike; Leibinger, Marco; Fischer, Dietmar

    2013-10-01

    Retinal ganglion cells (RGCs) do not normally regenerate injured axons. However, several strategies to transform RGCs into a potent regenerative state have been developed in recent years. Intravitreal CNTF application combined with conditional PTEN and SOCS3 deletion or zymosan-induced inflammatory stimulation together with cAMP analogue injection and PTEN-deletion in RGCs induce long-distance regeneration into the optic nerve of adult mice. A recent paper by the Benowitz group (de Lima et al.) claimed that the latter treatment enables full-length regeneration, with axons correctly navigating to their central target zones and partial recovery of visual behaviors. To gain a more detailed view of the extent and the trajectories of regenerating axons, Luo et al. applied a tissue clearing method and fluorescent microscopy to allow the tracing of naïve and regenerating RGC axons in whole ON and all the way to their brain targets. Using this approach, the authors found comparable axon regeneration in the optic nerve after both above-mentioned experimental treatments. Regeneration was accompanied by prevalent aberrant axon growth in the optic nerve and significant axonal misguidance at the optic chiasm. Less than 120 axons per animal reached the optic chiasm and only few entered the correct optic tract. Importantly, no axons reached visual targets in the olivary pretectal nucleus, the lateral geniculate nucleus or the superior colliculus, thereby contradicting and challenging previous claims by the Benowitz group. The data provided by Luo et al. rather suggest that potent stimulation of axonal growth per se is insufficient to achieve functional recovery and underscore the need to investigate regeneration-relevant axon guidance mechanisms in the mature visual system. PMID:23816572

  12. Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Hicks, Chindo; Sitthi-Amorn, Jitsuda; Douglas, Jessica; Ramani, Ritika; Miele, Lucio; Vijayakumar, Vani; Karlson, Cynthia; Chipeta, James; Megason, Gail

    2016-01-01

    Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL. PMID:26997880

  13. Central Nervous System Viral Invasion and Inflammation During Acute HIV Infection

    PubMed Central

    Valcour, Victor; Chalermchai, Thep; Sailasuta, Napapon; Marovich, Mary; Lerdlum, Sukalaya; Suttichom, Duanghathai; Suwanwela, Nijasri C.; Jagodzinski, Linda; Michael, Nelson; Spudich, Serena; van Griensven, Frits; de Souza, Mark; Kim, Jerome; Ananworanich, Jintanat

    2012-01-01

    Background. Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans. Methods. Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization. Results. HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285 651, 2321, and 81 978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log10 copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ–induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS. Conclusions. CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection. PMID:22551810

  14. Evaluation of the acute cardiac and central nervous system effects of the fluorocarbon trifluoromethane in baboons

    SciTech Connect

    Branch, C.A.; Goldberg, D.A.; Ewing, J.R.; Butt, S.S.; Gayner, J.; Fagan, S.C.

    1994-12-31

    The gaseous fluorocarbon trifluoromethane has recently been investigated for its potential as an in vivo gaseous indicator for nuclear magnetic resonance studies of brain perfusion. Trifluoromethane may also have significant value as a replacement for chlorofluorocarbon fire retardants. Because of possible species-specific cardiotoxic and anesthetic properties, the toxicological evaluation of trifluoromethane in primates (Papio anubis) is necessary prior to its evaluation in humans. We report the acute cardiac and central nervous system effects of trifluoromethane in eight anesthetized baboons. A dose-response effect was established for respiratory rate, electroencephalogram, and cardiac sinus rate, which exhibited a stepwise decrease from 10% trifluoromethane. No spontaneous arrhythmias were noted, and arterial blood pressure remained unchanged at any inspired level. Intravenous epinephrine infusions (1 {mu}g/kg) induced transient cardiac arrhythmia in 1 animal only at 70% FC-23 (v/v) trifluoromethane. Trifluoromethane appears to induce mild dose-related physiological changes at inspired levels of 30% or more, indicative of an anesthetic effect. These data suggest that trifluoromethane may be safe to use in humans, without significant adverse acute effects, at an inspired level of 30%. 23 refs., 3 figs., 3 tabs.

  15. Evidence Report: Risk of Acute and Late Central Nervous System Effects from Radiation Exposure

    NASA Technical Reports Server (NTRS)

    Nelson, Gregory A.; Simonsen, Lisa; Huff, Janice L.

    2016-01-01

    Possible acute and late risks to the central nervous system (CNS) from galactic cosmic rays (GCR) and solar particle events (SPE) are concerns for human exploration of space. Acute CNS risks may include: altered cognitive function, reduced motor function, and behavioral changes, all of which may affect performance and human health. Late CNS risks may include neurological disorders such as Alzheimer's disease (AD), dementia and premature aging. Although detrimental CNS changes are observed in humans treated with high-dose radiation (e.g., gamma rays and 9 protons) for cancer and are supported by experimental evidence showing neurocognitive and behavioral effects in animal models, the significance of these results on the morbidity to astronauts has not been elucidated. There is a lack of human epidemiology data on which to base CNS risk estimates; therefore, risk projection based on scaling to human data, as done for cancer risk, is not possible for CNS risks. Research specific to the spaceflight environment using animal and cell models must be compiled to quantify the magnitude of CNS changes in order to estimate this risk and to establish validity of the current permissible exposure limits (PELs). In addition, the impact of radiation exposure in combination with individual sensitivity or other space flight factors, as well as assessment of the need for biological/pharmaceutical countermeasures, will be considered after further definition of CNS risk occurs.

  16. Critical role for the AIM2 inflammasome during acute central nervous system bacterial infection

    PubMed Central

    Hanamsagar, Richa; Aldrich, Amy; Kielian, Tammy

    2014-01-01

    Interleukin-1β (IL-1β) is essential for eliciting protective immunity during the acute phase of Staphylococcus aureus (S. aureus) infection in the central nervous system (CNS). We previously demonstrated that microglial IL-1β production in response to live S. aureus is mediated through the Nod-like receptor protein 3 (NLRP3) inflammasome, including the adapter protein ASC (apoptosis-associated, speck-like, caspase-1 recruiting domain-containing protein), and pro-caspase-1. Here we utilized NLRP3, ASC, and caspase-1/11 knockout (KO) mice to demonstrate the functional significance of inflammasome activity during CNS S. aureus infection. ASC and caspase-1/11 KO animals were exquisitely sensitive, with approximately 50% of mice succumbing to infection within 24 h. Unexpectedly, the survival of NLRP3 KO mice was similar to WT animals, suggesting the involvement of an alternative upstream sensor, which was later identified as absent in melanoma 2 (AIM2) based on the similar disease patterns between AIM2 and ASC KO mice. Besides IL-1β, other key inflammatory mediators, including IL-6, CXCL1, CXCL10, and CCL2 were significantly reduced in the CNS of AIM2 and ASC KO mice, implicating autocrine/paracrine actions of IL-1β, since these mediators do not require inflammasome processing for secretion. These studies demonstrate a novel role for the AIM2 inflammasome as a critical molecular platform for regulating IL-1β release and survival during acute CNS S. aureus infection. PMID:24484406

  17. Retinal Detachment Vision Simulator

    MedlinePlus

    ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment Vision Simulator Mar. 01, 2016 How does a detached or torn retina affect your vision? If a retinal tear is occurring, you may ...

  18. Two long-lasting central respiratory responses following acute hypoxia in glomectomized cats.

    PubMed

    Gallman, E A; Millhorn, D E

    1988-01-01

    1. Central respiratory response to acute (10 min) hypoxia, as measured by phrenic nerve activity, was determined in peripheral chemo-denervated cats. 2. Hypoxia was induced by ventilating cats for 10 min at reduced inspired oxygen levels (inspired O2 fraction, FI,O2 = 0.06-0.15). The degree of hypoxaemia was determined from an arterial blood sample and ranged from 'severe' (arterial O2 pressure, Pa,O2 less than 26 Torr) to 'mild' (Pa,O2 greater than 35 Torr). The respiratory response was monitored for 1 h following return to ventilation with 100% oxygen. 3. The results confirmed the finding of prolonged (greater than 60 min) inhibition of respiration upon return to hyperoxic conditions following severe hypoxia, as reported previously (Millhorn, Eldridge, Kiley & Waldrop, 1984). A new finding was a long-lasting (greater than 60 min) facilitation of respiration following exposure to less severe (Pa,O2 greater than 35 Torr) hypoxia. 4. Medullary extracellular fluid pH was measured in six cats. Changes in pH could not explain either the prolonged inhibition following severe hypoxia or the long-lasting facilitation observed following mild hypoxia. 5. Ablation studies were performed in order to determine the locations of the neuronal substrates for the inhibitory and facilitatory mechanisms. The results of this series of experiments indicate that the mesencephalon is necessary for activation of the inhibitory mechanism, while the facilitatory mechanism requires the presence of higher brain structures, notably the diencephalon. 6. Following removal of the diencephalon, the inhibitory response was seen following even mild hypoxic insults, i.e. those shown to produce facilitation in animals with intact brains. In the absence of the mesencephalon, neither prolonged inhibition nor prolonged facilitation could be produced following hypoxia. 7. It is proposed that there are two centrally mediated long-lasting responses to acute hypoxia. Facilitation is seen following mild

  19. Is the outcome in acute aortic dissection type A influenced by of femoral versus central cannulation?

    PubMed Central

    Bucsky, Bence S.; Richardt, Doreen; Petersen, Michael; Sievers, Hans H.

    2016-01-01

    Background The purpose of this study was to evaluate the single-center experience in initial femoral versus central cannulation of the extracorporeal circulation for acute aortic dissection type A (AADA). Methods Between January 2003 and December 2015, 235 patients underwent repair of AADA. All patients were evaluated for the type of arterial cannulation (femoral vs. central) for initial bypass. Demographic data and outcome parameters were accessed. Results One hundred and twenty seven (54.0%) were initially cannulated in the central aortic vessels (ascending aorta or subclavian/axillary artery) and 108 (46.0%) in the femoral artery. Patients were comparable between age (62.4±14.4 vs. 62.9±14.4 years, P=0.805), gender (male, 62.2 vs. 69.4%, P=0.152) and previous sternotomy (15.7 vs. 16.7%, P=0.861) between both cannulation groups; while EuroSCORE I (11.5±4.0 vs. 12.7±4.2, P=0.031) and ASA Score (3.5±0.81 vs. 3.8±0.57, P=0.011) were significantly higher in the femoral artery cannulation group. Bypass (249±102 vs. 240±81 min, P=0.474), X-clamp (166±85 vs. 157±67 min, P=0.418) and circulatory arrest time (51.6±28.7 vs. 48.3±21.7 min, P=0.365) were similar between the groups as were lowest temperature (18.1±2.0 vs. 18.1±2.2, P=0.775). Postoperative neurologic deficit and 30-day mortality were comparable between both cannulation groups (11.7 vs. 7.2%, P=0.449 and 20.2 vs. 16.9%, P=0.699, central vs. peripheral cannulation). Multivariate analysis revealed only EuroScore I above 13 as single preoperative predictor for mortality. Conclusions AADA can be operated with both femoral and central cannulation with similar results. Risk for early mortality was driven by the preoperative clinical and hemodynamic status before operation rather than the cannulation technique. PMID:27563543

  20. [Novel mechanism for retinal vascular diseases].

    PubMed

    Suzuma, Kiyoshi

    2015-03-01

    I. A new therapeutic target for diabetic retinopathy. Recent reports state that succinate may be an independent retinal angiogenic factor. We evaluated concentrations in vitreous from proliferative diabetic retinopathy (PDR), and found that succinate increased significantly in PDR. Interestingly, levels of succinate from bevacizumab-pre-injected PDR were normal, suggesting that vascular endothelial growth factor (VEGF) had a positive feedback mechanism for succinate since succinate was previously reported to induce VEGF. II. A new understanding of central retinal vein occlusion (CRVO). We evaluated retinal blood flow velocity with laser speckle flowgraphy (LSFG) made in Japan, and found that cases in which both macular edema and retinal blood flow velocity improved after anti-VEGF therapy had better prognosis. In ischemic CRVO at final visit, mean retinal blood velocity was less than 50% of fellow eyes after 1st anti-VEGF therapy, suggesting that those cases might have poor prognosis. LSFG is useful for evaluation and decision in CRVO treatment. III. From exploration for mechanism in retinal vascular diseases to re-vascularization therapy. The standard treatment for retinal non-perfusion area is scatter laser photocoagulation, which is both invasive of the peripheral retina and may prove destructive. Re-vascularization is an ideal strategy for treatment of retinal non-perfusion area. To develop a new methods for re-vascularization in retinal non-perfusion area, we have designed experiments using a retina without vasculature differentiated from induced pluripotent stem(iPS) cells. PMID:25854111

  1. Hyperosmolar and methotrexate therapy avoiding surgery in the acute presentation of primary central nervous system lymphoma

    PubMed Central

    Lee, Bryan S.; Juthani, Rupa G.; Healy, Andrew T.; Peereboom, David M.; Recinos, Violette M.

    2014-01-01

    Background: Primary central nervous system lymphoma (PCNSL) is an aggressive type of extra-nodal non-Hodgkin lymphoma. Without treatment, PCNSL is associated with significant morbidity and mortality, including rapid neurological deterioration. In contrast to other high-grade intracranial neoplasms, PCNSL is considered to have a high response rate to conventional medical therapy, especially in younger patients, and therefore warrants particular attention in terms of nonsurgical treatment. Case Description: We report a case of the medical management of acute deterioration due to rapidly growing PCNSL with mass effect to highlight the efficacy of temporization with hyperosmolar therapy while awaiting the known rapid effects of dexamethasone and methotrexate (MTX) treatment. Surgical intervention was avoided, and tumor response was rapid. The patient had corresponding clinical resolution of symptoms of elevated intracranial pressure with return to neurologic baseline. Conclusions: Despite the evidence that PCNSL responds well to steroids and MTX, the rapidity of onset with which this occurs can vary. In patients presenting with mass effect and rapid neurologic decline, there is little evidence to support medical over surgical intervention. Herein we present an illustrative case of a large PCNSL lesion presenting with rapid decline. With clinical improvement in one day and a 50% reduction in tumor volume over less than seven days, the authors present the specific time frame with which PCNSL responds to medical therapy and a safe strategy for medical temporization. PMID:25184099

  2. Mitochondria Play a Central Role in Nonischemic Cardiomyocyte Necrosis: Common to Acute and Chronic Stressor States

    PubMed Central

    Khan, M. Usman; Cheema, Yaser; Shahbaz, Atta U.; Ahokas, Robert A.; Sun, Yao; Gerling, Ivan C.; Bhattacharya, Syamal K.; Weber, Karl T.

    2012-01-01

    The survival of cardiomyocytes must be ensured as the myocardium adjusts to a myriad of competing physiologic and pathophysiologic demands. A significant loss of these contractile cells, together with their replacement by stiff fibrillar collagen in the form of fibrous tissue accounts for a transition from a usually efficient muscular pump into one that is failing. Cellular and subcellular mechanisms involved in the pathogenic origins of cardiomyocyte cell death have long been of interest. This includes programmed molecular pathways to either necrosis or apoptosis which are initiated from ischemic or nonischemic origins. Herein we focus on the central role played by a mitochondriocentric signal-transducer-effector pathway to nonischemic cardiomyocyte necrosis which is common to acute and chronic stressor states. We begin by building upon the hypothesis advanced by Albrecht Fleckenstein and coworkers some 40 years ago based on the importance of calcitropic hormone- mediated intracellular Ca2+ overloading which predominantly involves subsarcolemmal mitochondria and is the signal to pathway activation. Other pathway components, which came to be recognized in subsequent years, include the induction of oxidative stress and opening of the mitochondrial inner membrane permeability transition pore. The ensuing loss of cardiomyocytes and consequent replacement fibrosis, or scarring, represents a disease of adaptation and a classic example of when homeostasis begets dyshomeostasis. PMID:22328074

  3. Mitochondria play a central role in nonischemic cardiomyocyte necrosis: common to acute and chronic stressor states.

    PubMed

    Khan, M Usman; Cheema, Yaser; Shahbaz, Atta U; Ahokas, Robert A; Sun, Yao; Gerling, Ivan C; Bhattacharya, Syamal K; Weber, Karl T

    2012-07-01

    The survival of cardiomyocytes must be ensured as the myocardium adjusts to a myriad of competing physiological and pathophysiological demands. A significant loss of these contractile cells, together with their replacement by stiff fibrillar collagen in the form of fibrous tissue accounts for a transition from a usually efficient muscular pump into one that is failing. Cellular and subcellular mechanisms involved in the pathogenic origins of cardiomyocyte cell death have long been of interest. This includes programmed molecular pathways to either necrosis or apoptosis, which are initiated from ischemic or nonischemic origins. Herein, we focus on the central role played by a mitochondriocentric signal-transducer-effector pathway to nonischemic cardiomyocyte necrosis, which is common to acute and chronic stressor states. We begin by building upon the hypothesis advanced by Albrecht Fleckenstein and coworkers some 40 years ago based on the importance of calcitropic hormone-mediated intracellular Ca(2+) overloading, which predominantly involves subsarcolemmal mitochondria and is the signal to pathway activation. Other pathway components, which came to be recognized in subsequent years, include the induction of oxidative stress and opening of the mitochondrial inner membrane permeability transition pore. The ensuing loss of cardiomyocytes and consequent replacement fibrosis, or scarring, represents a disease of adaptation and a classic example of when homeostasis begets dyshomeostasis. PMID:22328074

  4. Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections

    PubMed Central

    Tan, Le Van; van Doorn, H. Rogier; Nghia, Ho Dang Trung; Chau, Tran Thi Hong; Tu, Le Thi Phuong; de Vries, Michel; Canuti, Marta; Deijs, Martin; Jebbink, Maarten F.; Baker, Stephen; Bryant, Juliet E.; Tham, Nguyen Thi; BKrong, Nguyen Thi Thuy Chinh; Boni, Maciej F.; Loi, Tran Quoc; Phuong, Le Thi; Verhoeven, Joost T. P.; Crusat, Martin; Jeeninga, Rienk E.; Schultsz, Constance; Chau, Nguyen Van Vinh; Hien, Tran Tinh; van der Hoek, Lia; Farrar, Jeremy; de Jong, Menno D.

    2013-01-01

    ABSTRACT Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus. PMID:23781068

  5. Central nervous system haemorrhage causing early death in acute promyelocytic leukaemia

    PubMed Central

    Borowska, Anna; Stelmaszczyk-Emmel, Anna

    2016-01-01

    Acute promyelocytic leukaemia (APL) is a rare type of paediatric leukaemia characterised by a specific genetic mutation and life-threatening coagulopathy. The discovery of all-trans retinoic acid (ATRA), which acts directly on promyelocytic locus-retinoic acid receptor α (PML-RARα) gene product, brought a revolution to the therapy of this disorder. Unfortunately, despite an improvement in the complete remission rate, the early death (ED) rate has not changed significantly, and the haemorrhages remain a major problem. The most common bleeding site, which accounts for about 65-80% of haemorrhages, is the central nervous system. Second in line are pulmonary haemorrhages (32%), while gastrointestinal bleedings are relatively rare. Haemorrhages result from thrombocytopaenia, disseminated intravascular coagulopathy (DIC), and systemic fibrinolysis. Herein we present a boy aged one year and nine months with APL. The patient was not eligible for ATRA administration due to poor clinical condition. He developed bleeding diathesis that presented as disseminated intravascular coagulation (DIC) and led to intracranial haemorrhage, which resulted in the patient's death. PMID:26862315

  6. Central Nervous System Involvement in Adult Acute Lymphoblastic Leukemia: Diagnostic Tools, Prophylaxis, and Therapy

    PubMed Central

    Del Principe, Maria Ilaria; Maurillo, Luca; Buccisano, Francesco; Sconocchia, Giuseppe; Cefalo, Mariagiovanna; De Santis, Giovanna; Di Veroli, Ambra; Ditto, Concetta; Nasso, Daniela; Postorino, Massimiliano; Refrigeri, Marco; Attrotto, Cristina; Del Poeta, Giovanni; Lo-Coco, Francesco; Amadori, Sergio; Venditti, Adriano

    2014-01-01

    In adult patients with acute lymphoblastic leukemia (ALL), Central Nervous System (CNS) involvement is associated with a very poor prognosis. The diagnostic assessment of this condition relies on the use of neuroradiology, conventional cytology (CC) and flow cytometry (FCM). Among these approaches, which is the gold standard it is still a matter of debate. Neuroradiology and CC have a limited sensitivity with a higher rate of false negative results. FCM demonstrated a superior sensitivity over CC, particularly when low levels of CNS infiltrating cells are present. Although prospective studies of a large series of patients are still awaited, a positive finding by FCM appears to anticipate an adverse outcome even if CC shows no infiltration. Current strategies for adult ALL CNS-directed prophylaxis or therapy involve systemic and intrathecal chemotherapy and radiation therapy. An early and frequent intrathecal injection of cytostatic combined with systemic chemotherapy is the most effective strategy to reduce the frequency of CNS involvement. In patients with CNS overt ALL, at diagnosis or upon relapse, allogeneic hematopoietic stem cell transplantation might be considered. This review discusses risk factors, diagnostic techniques for identification of CNS infiltration and modalities of prophylaxis and therapy to manage it. PMID:25408861

  7. Glucose intolerance induced by blockade of central FGF receptors is linked to an acute stress response

    PubMed Central

    Rojas, Jennifer M.; Matsen, Miles E.; Mundinger, Thomas O.; Morton, Gregory J.; Stefanovski, Darko; Bergman, Richard N.; Kaiyala, Karl J.; Taborsky, Gerald J.; Schwartz, Michael W.

    2015-01-01

    iv glucose (given during the FSIGT) contributed to the rapid resolution of the sympathoadrenal response induced by icv FGFRi, we performed an additional study comparing groups that received iv saline or iv glucose 30 min after icv FGFRi. Our finding that elevated plasma catecholamine levels returned rapidly to baseline irrespective of whether rats subsequently received an iv bolus of saline or glucose indicates that the rapid reversal of sympathoadrenal activation following icv FGFRi was unrelated to the subsequent glucose bolus. Conclusions The effect of acute inhibition of central FGFR signaling to impair glucose tolerance likely involves a stress response associated with pronounced, but transient, sympathoadrenal activation and an associated reduction of insulin secretion. Whether this effect is a true consequence of FGFR blockade or involves an off-target effect of the FGFR inhibitor requires additional study. PMID:26266088

  8. Fate of Central Venous Catheters Used for Acute Extracorporeal Treatment in Critically Ill Pediatric Patients: A Single Center Experience.

    PubMed

    Rus, Rina R; Premru, Vladimir; Novljan, Gregor; Grošelj-Grenc, Mojca; Ponikvar, Rafael

    2016-06-01

    Renal replacement treatment (RRT) is required in severe acute kidney injury, and a functioning central venous catheter (CVC) is crucial. Twenty-eight children younger than 16 years have been treated at the University Medical Centre Ljubljana between 2003 and 2012 with either acute hemodialysis (HD) and/or plasma exchange (PE), and were included in our study. The age of the patients ranged from 2 days to 14.1 years. Sixty-six CVCs were inserted (52% de novo, 48% guide wire). The sites of insertion were the jugular vein in 20% and the femoral vein in 80%. Catheters were in function from 1 day to 27 days. The most common cause for CVC removal or exchange was catheter dysfunction (50%). CVCs were mostly inserted in the femoral vein, which is the preferred site of insertion in acute HD/PE because of the smaller number of complications. PMID:27312920

  9. Unilateral acute idiopathic maculopathy. 1991.

    PubMed

    Yannuzzi, Lawrence A; Jampol, Lee M; Rabb, Maurice F; Sorenson, John A; Beyrer, Charles; Wilcox, Lloyd M

    2012-02-01

    This is a report of nine patients who experienced sudden, severe, unilateral central vision loss following a flulike illness. Each patient had an exudative detachment of the macula. All patients experienced a spontaneous resolution of the acute macular manifestations with near-complete recovery of vision. A characteristic "bull's-eye" appearance in the macula persisted. The acute manifestations of the disorder did not recur in any of the patients during the period of follow-up. The constellation of findings was suggestive of an inflammatory disease of the retinal pigment epithelium, but a specific causative agent could not be identified. The acute clinical and angiographic features, the natural course, and the residual pigment epithelial derangement were not consistent with any previously described disorder. PMID:22451959

  10. Factors Predicting the Effects of Hybrid Assistive Limb Robot Suit during the Acute Phase of Central Nervous System Injury

    PubMed Central

    CHIHARA, Hideo; TAKAGI, Yasushi; NISHINO, Kazunari; YOSHIDA, Kazumichi; ARAKAWA, Yoshiki; KIKUCHI, Takayuki; TAKENOBU, Yohei; MIYAMOTO, Susumu

    2016-01-01

    To improve the activities of daily living of patients with injury to the central nervous system, physical therapy starting from the acute phase of the injury is important. Recently, the efficacy of physical therapy using a hybrid assistive limb (HAL) robot suit was reported. However, individual differences exist in the effects of HAL. We investigated factors predicting the effects of HAL in 15 patients at our institution with central nervous system injury, primarily due to stroke, who underwent training using HAL during the acute phase. Patients were classified as either “with HAL suitability” or “without HAL suitability” based on scores from 10-m walking speed, gait, satisfaction, and pain. In both groups, Brunnstrom stage before HAL intervention, Fugl-Meyer assessment (FMA), stroke impairment assessment set (SIAS), and functional independence measure (FIM) were evaluated. Although motor function items did not differ significantly, FIM cognitive function items (P = 0.036), visuospatial perception items on SIAS (P = 0.0277), and pain items on SIAS (P = 0.0122) differed significantly between groups. These results indicated that training using HAL does not involve pain in patients with central nervous system injury during the acute phase, and exhibits positive effects in patients without pain and with high communication ability and visuospatial perception function. When conducting HAL intervention, incorporating functional assessment scores (FIM and SIAS), including peripheral items, may be useful to predict the suitability of HAL. PMID:26538291

  11. Central nervous system effects of meclizine and dimenhydrinate: evidence of acute tolerance to antihistamines.

    PubMed

    Manning, C; Scandale, L; Manning, E J; Gengo, F M

    1992-11-01

    Relative daytime drowsiness and performance impairment produced by meclizine and dimenhydrinate was assessed in 24 healthy male volunteers. Subjects received either dimenhydrinate, 100 mg, at 8:00 AM, 12:00 PM, and 4:00 PM; meclizine, 50 mg, at 8:00 AM, with placebo at 12:00 PM and 4:00 PM; or placebo at all three times in this randomized, double-blind, three-way crossover study. Impairment of mental performance was assessed by choice reaction time testing and digit symbol substitution scores. Drowsiness was self-assessed on the Stanford Sleepiness Scale and on a visual analog scale. Both antihistamines produced changes in digit symbol substitution, recognition time, and subjective assessments of sleepiness different from placebo. Expressed as change from baseline, the greatest reductions in digit symbol substitution scores after dimenhydrinate occurred 3 hours after the first dose (6.6 +/- 7) and were not different from the greatest measured change after meclizine (5.8 +/- 8), which occurred 9 hours after the dose was administered. Similar results were obtained with the other psychometric test scores. Self-rated sleepiness after dimenhydrinate was greatest 1 hour after the first dose, and was significantly greater than the largest degree of sleepiness after meclizine, which occurred at 7 hours after the dose. The effects of the first dose of dimenhydrinate on psychometric test scores were compared with the magnitude of the effects produced by subsequent doses. The magnitude of effect of the first dose of dimenhydrinate was significantly greater than the magnitude of effect produced by subsequent doses. The data suggest the possibility that acute tolerance to central nervous system impairment develops with multiple doses of dimenhydrinate. PMID:1474173

  12. Neurogenic stunned myocardium - do we consider this diagnosis in patients with acute central nervous system injury and acute heart failure?

    PubMed

    Mierzewska-Schmidt, Magdalena; Gawecka, Agnieszka

    2015-01-01

    Neurogenic stunned myocardium (NSM) is defined as myocardial injury and dysfunction of a sudden onset, occurring after various types of acute brain injury as a result of an imbalance in the autonomic nervous system. The typical spectrum of clinically observed abnormalities includes acute left ventricular failure, not uncommonly progressing to cardiogenic shock with hypotension that requires inotropic agents, pulmonary oedema and various arrhythmias. Commonly-seen electrocardiographic changes include: prolonged QT interval, ST segment changes, T-wave inversion, a new Q-wave or U-wave. Echocardiography shows both an impaired both systolic and diastolic function of the left ventricle. Biochemical markers of NSM comprise metabolic acidosis and increased cardiac enzymes and markers: creatine kinase (CK), and CK-MB, troponin I and B-type natriuretic peptide. The main cause of NSM is myocardial injury induced by local catecholamine release from nerve endings within the myocardium. Recently, a theory has been proposed to classify NSM as one of the stress-related cardiomyopathies, together with Takotsubo cardiomyopathy, acute left ventricular failure in the critically ill, cardiomyopathy associated with pheochromacytoma and exogenous catecholamine administration. The occurrence of NSM increases the risk of life-threatening complications, death, and worsens neurologic outcome. As far as we know, treatment should generally focus on the underlying neurologic process in order to maximize neurologic recovery. Improvement in neurologic pathology leads to rapid improvement in cardiac function and its full recovery, as NSM is a fully reversible condition if the patient survives. Awareness of the existence of NSM and a deeper knowledge of its etiopathology may reduce diagnostic errors, optimise its treatment. PMID:25940334

  13. Role of central arginine vasopressin receptors in the analgesic effect of CDP-choline on acute and neuropathic pain.

    PubMed

    Bagdas, Deniz; Yucel-Ozboluk, Hasret; Orhan, Fulya; Kanat, Ozkan; Isbil-Buyukcoskun, Naciye; Gurun, Mine S

    2013-12-01

    Recent studies have demonstrated that arginine vasopressin (AVP) plays a crucial role in pain modulation. In addition, our previous studies have proven that centrally administered cytidine-5'-diphosphate-choline (CDP-choline; citicoline) elicits an analgesic effect in different pain models in rats. Given that CDP-choline enhances central and peripheral vasopressin levels, the present study was designed to investigate the role of central AVP receptors in the analgesic effect of CDP-choline in acute and chronic constriction injury-induced neuropathic pain models. For this purpose, rats were pretreated intracerebroventricularly with the AVP V1 or AVP V2 receptor antagonist 15 min before intracerebroventricular injection of CDP-choline or saline, and pain threshold was determined using the Randall-Selitto test. AVP V1 and AVP V2 receptor antagonist blocked the CDP-choline-induced analgesic effect either in acute or neuropathic models of pain in rats. These results suggest, for the first time, that central AVP receptors are involved in the CDP-choline-elicited analgesic effect. PMID:24089014

  14. The neuroprotective effect of hyperbaric oxygen treatment on laser-induced retinal damage in rats

    NASA Astrophysics Data System (ADS)

    Vishnevskia-Dai, Victoria; Belokopytov, Mark; Dubinsky, Galina; Nachum, Gal; Avni, Isaac; Belkin, Michael; Rosner, Mordechai

    2005-04-01

    Retinal damage induced by mechanical trauma, ischemia or laser photocoagulation increases considerably by secondary degeneration processes. The spread of damage may be ameliorated by neuroprotection that is aimed at reducing the extent of the secondary degeneration and promote healing processes. Hyperbaric oxygen (HBO) treatment consists of inspiration of oxygen at higher than one absolute atmospheric pressure. Improved neural function was observed in patients with acute brain trauma or ischemia treated with HBO. This study was designed to evaluate the neuroprotective effect of hyperbaric oxygen (HBO) on laser induced retinal damage in a rat model. Standard argon laser lesions were created in 25 pigmented rats divided into three groups: Ten rats were treated immediately after the irradiation with HBO three times during the first 24 hr followed by 12 consecutive daily treatments. Five rats received a shorter treatment regimen of 10 consecutive HBO treatments. The control group (10 rats) underwent the laser damage with no additional treatment. The retinal lesions were evaluated 20 days after the injury. All outcome measures were improved by the longer HBO treatment (P<0.01). The shorter HBO treatment was less effective, showing an increase only in nuclei density at the central area of lesion (P< 0.01). Hyperbaric oxygen seems to exert a neuroprotective effect on laser-induced retinal damage in a rat model. In the range of HBO exposures studied, longer exposure provides more neuroprotection. These results encourage further evaluation of the potential therapeutic use of hyperbaric oxygen in diseases and injuries of the retina.

  15. Pars Plana Vitrectomy Combined with Internal Limiting Membrane Peeling to Treat Persistent Macular Edema after Anti-Vascular Endothelial Growth Factor Treatment in Cases of Ischemic Central Retinal Vein Occlusion

    PubMed Central

    Shirakata, Yukari; Fujita, Tomoyoshi; Nakano, Yuki; Shiraga, Fumio; Tsujikawa, Akitaka

    2016-01-01

    Objective To evaluate the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) peeling in cases of ischemic central retinal vein occlusion (CRVO) where macular edema (ME) persisted after anti-vascular endothelial growth factor (anti-VEGF) treatment. Methods Fifteen eyes with ischemic CRVO-related ME were included in the study. Nine were treated with panretinal photocoagulation after initial examination. Anti-VEGF agents were injected intravitreally. Persistent ME was treated with PPV combined with ILM peeling. During surgery, laser photocoagulation was further applied to the non-perfused area. Results Mean retinal thickness gradually decreased after surgery (p = 0.024 at 6 months), although visual acuity did not improve significantly during the follow-up period (14.7 ± 11.6 months). Neovascular glaucoma subsequently developed in three cases and a trabeculectomy was performed in one case. Conclusion In eyes with ischemic CRVO, PPV combined with ILM peeling contributed to a reduction in persistent ME. However, there was no significant improvement in visual acuity. PMID:26889152

  16. Metamorphopsia Associated with Branch Retinal Vein Occlusion

    PubMed Central

    Manabe, Koichiro; Tsujikawa, Akitaka; Osaka, Rie; Nakano, Yuki; Fujita, Tomoyoshi; Shiragami, Chieko; Hirooka, Kazuyuki; Uji, Akihito; Muraoka, Yuki

    2016-01-01

    Purpose To apply M-CHARTS for quantitative measurements of metamorphopsia in eyes with acute branch retinal vein occlusion (BRVO) and to elucidate the pathomorphology that causes metamorphopsia. Methods This prospective study consisted of 42 consecutive patients (42 eyes) with acute BRVO. Both at baseline and one month after treatment with ranibizumab, metamorphopsia was measured with M-CHARTS, and the retinal morphological changes were examined with optical coherence tomography. Results At baseline, metamorphopsia was detected in the vertical and/or horizontal directions in 29 (69.0%) eyes; the mean vertical and horizontal scores were 0.59 ± 0.57 and 0.52 ± 0.67, respectively. The maximum inner retinal thickness showed no association with the M-CHARTS score, but the M-CHARTS score was correlated with the total foveal thickness (r = 0.43, p = 0.004), the height of serous retinal detachment (r = 0.31, p = 0.047), and the maximum outer retinal thickness (r = 0.36, p = 0.020). One month after treatment, both the inner and outer retinal thickness substantially decreased. However, metamorphopsia persisted in 26 (89.7%) of 29 eyes. The posttreatment M-CHARTS score was not correlated with any posttreatment morphological parameters. However, the posttreatment M-CHARTS score was weakly correlated with the baseline total foveal thickness (r = 0.35. p = 0.024) and closely correlated with the baseline M-CHARTS score (r = 0.78, p < 0.001). Conclusions Metamorphopsia associated with acute BRVO was quantified using M-CHARTS. Initial microstructural changes in the outer retina from acute BRVO may primarily account for the metamorphopsia. PMID:27123642

  17. Clinical presentation, etiology, and survival in adult acute encephalitis syndrome in rural Central India

    PubMed Central

    Joshi, Rajnish; Mishra, Pradyumna Kumar; Joshi, Deepti; Santhosh, SR; Parida, M.M.; Desikan, Prabha; Gangane, Nitin; Kalantri, S.P.; Reingold, Arthur; Colford, John M.

    2013-01-01

    Background Acute encephalitis syndrome (AES) is a constellation of symptoms that includes fever and altered mental status. Most cases are attributed to viral encephalitis (VE), occurring either in outbreaks or sporadically. We conducted hospital-based surveillance for sporadic adult-AES in rural Central India in order to describe its incidence, spatial and temporal distribution, clinical profile, etiology and predictors of mortality. Methods All consecutive hospital admissions during the study period were screened to identify adult-AES cases and were followed until 30-days of hospitalization. We estimated incidence by administrative sub-division of residence and described the temporal distribution of cases. We performed viral diagnostic studies on cerebrospinal fluid (CSF) samples to determine the etiology of AES. The diagnostic tests included RT-PCR (for enteroviruses, HSV 1 and 2), conventional PCR (for flaviviruses), CSF IgM capture ELISA (for Japanese encephalitis virus, dengue, West Nile virus, Varicella zoster virus, measles, and mumps). We compared demographic and clinical variables across etiologic subtypes and estimated predictors of 30-day mortality. Results A total of 183 AES cases were identified between January and October 2007, representing 2.38% of all admissions. The incidence of adult AES in the administrative subdivisions closest to the hospital was 16 per 100,000. Of the 183 cases, a non-viral etiology was confirmed in 31 (16.9%) and the remaining 152 were considered as VE suspects. Of the VE suspects, we could confirm a viral etiology in 31 cases: 17 (11.2%) enterovirus; 8 (5.2%) flavivirus; 3 (1.9%) Varicella zoster; 1 (0.6%) herpesvirus; and 2 (1.3%) mixed etiology); the etiology remained unknown in remaining 121 (79.6%) cases. 53 (36%) of the AES patients died; the case fatality proportion was similar in patients with a confirmed and unknown viral etiology (45.1 and 33.6% respectively). A requirement for assisted ventilation significantly

  18. Intravitreal Anti-vascular Endothelial Growth Factor versus Observation in Acute Central Serous Chorioretinopathy: One-year Results

    PubMed Central

    Park, Sang-Uk; Lee, Seung-Jun

    2014-01-01

    Purpose To evaluate the efficacy of anti-vascular endothelial growth factor (VEGF) compared with observation for treating acute central serous chorioretinopathy (CSC). Methods A retrospective study of 36 patients with acute CSC, including 21 patients treated with anti-VEGF (anti-VEGF group) and 15 patients with observation (observation group). Patients in the anti-VEGF group received a single dose of bevacizumab or ranibizumab at baseline. Best-corrected visual acuity (BCVA), central foveal thickness (CFT) and resolution of subretinal fluid (SRF) on optical coherence tomography (OCT) were assessed. The integrity of the foveal inner segment/outer segment (IS/OS) line at 12 months was also analyzed. Results Resolution of SRF was achieved in 20 of 21 eyes in the anti-VEGF group and in 12 of 15 eyes in the observation group (p = 0.151). Mean BCVA and CFT were not different between the two groups at 12 months (p > 0.05). The amount of change in BCVA, however, differed significantly between the groups (p = 0.044). Final OCT more frequently detected the foveal IS/OS line in the anti-VEGF group than in the observation group (p = 0.012). Conclusions In terms of BCVA, anti-VEGF and observation only had similar therapeutic effects in acute CSC patients. In some patients, however, the rapid resolution of SRF by anti-VEGF might reduce the risk of photoreceptor degeneration and improve long-term visual acuity. PMID:25120339

  19. The K(+)-Cl(-) Cotransporter KCC2 and Chloride Homeostasis: Potential Therapeutic Target in Acute Central Nervous System Injury.

    PubMed

    Wu, Haijian; Che, Xiaoru; Tang, Junjia; Ma, Feiqiang; Pan, Kun; Zhao, Mingfei; Shao, Anwen; Wu, Qun; Zhang, Jianmin; Hong, Yuan

    2016-05-01

    The K(+)-Cl(-) cotransporter-2 (KCC2) is a well-known member of the electroneutral cation-chloride cotransporters with a restricted expression pattern to neurons. This transmembrane protein mediates the efflux of Cl(-) out of neurons and exerts a critical role in inhibitory γ-aminobutyric acidergic (GABAergic) and glycinergic neurotransmission. Moreover, KCC2 participates in the regulation of various physiological processes of neurons, including cell migration, dendritic outgrowth, spine morphology, and dendritic synaptogenesis. It is important to note that down-regulation of KCC2 is associated with the pathogenesis of multiple neurological diseases, which is of particular relevance to acute central nervous system (CNS) injury. In this review, we aim to survey the pathogenic significance of KCC2 down-regulation under the condition of acute CNS injuries. We propose that further elucidation of the molecular mechanisms regarding KCC2 down-regulation after acute CNS injuries is necessary because of potential promising avenues for prevention and treatment of acute CNS injury. PMID:25941074

  20. Acute tianeptine treatment selectively modulates neuronal activation in the central nucleus of the amygdala and attenuates fear extinction.

    PubMed

    Godsil, B P; Bontempi, B; Mailliet, F; Delagrange, P; Spedding, M; Jay, T M

    2015-11-01

    Antidepressant drugs are commonly prescribed treatments for anxiety disorders, and there is growing interest in understanding how these drugs impact fear extinction because extinction learning is pivotal to successful exposure-based therapy (EBT). A key objective within this domain is understanding how antidepressants alter the activation of specific elements of the limbic-based network that governs such fear processing. Chronic treatment with the antidepressant tianeptine has been shown to reduce the acquisition of extinction learning in rats, yet the drug's acute influence on activation in prefrontal and amygdalar regions, and on extinction learning are not well understood. To assess its influence on cellular activation, rats were injected with tianeptine and Fos immunoreactivity was measured in these regions. Acute tianeptine treatment selectively altered Fos expression within subdivisions of the central nucleus of the amygdala (CEA) in a bidirectional manner that varied in relation to ongoing activation within the capsular subdivision and its prefrontal and intra-amygdalar inputs. This pattern of results suggests that the drug can conditionally modulate the activation of CEA subdivisions, which contain microcircuits strongly implicated in fear processing. The effect of acute tianeptine was also examined with respect to the acquisition, consolidation and expression of fear extinction in rats. Acute tianeptine attenuated extinction learning as well as the recall of extinction memory, which underscores that acute dosing with the drug could alter learning during EBT. Together these findings provide a new perspective for understanding the mechanism supporting tianeptine's clinical efficacy, as well as its potential influence on CEA-based learning mechanisms. PMID:25560759

  1. Purinergic signaling in retinal degeneration and regeneration.

    PubMed

    Reichenbach, Andreas; Bringmann, Andreas

    2016-05-01

    Purinergic signaling is centrally involved in mediating the degeneration of the injured and diseased retina, the induction of retinal gliosis, and the protection of the retinal tissue from degeneration. Dysregulated calcium signaling triggered by overactivation of P2X7 receptors is a crucial step in the induction of neuronal and microvascular cell death under pathogenic conditions like ischemia-hypoxia, elevated intraocular pressure, and diabetes, respectively. Overactivation of P2X7 plays also a pathogenic role in inherited and age-related photoreceptor cell death and in the age-related dysfunction and degeneration of the retinal pigment epithelium. Gliosis of micro- and macroglial cells, which is induced and/or modulated by purinergic signaling and associated with an impaired homeostatic support to neurons, and the ATP-mediated propagation of retinal gliosis from a focal injury into the surrounding noninjured tissue are involved in inducing secondary cell death in the retina. On the other hand, alterations in the glial metabolism of extracellular nucleotides, resulting in a decreased level of ATP and an increased level of adenosine, may be neuroprotective in the diseased retina. Purinergic signals stimulate the proliferation of retinal glial cells which contributes to glial scarring which has protective effects on retinal degeneration and adverse effects on retinal regeneration. Pharmacological modulation of purinergic receptors, e.g., inhibition of P2X and activation of adenosine receptors, may have clinical importance for the prevention of photoreceptor, neuronal, and microvascular cell death in diabetic retinopathy, retinitis pigmentosa, age-related macular degeneration, and glaucoma, respectively, for the clearance of retinal edema, and the inhibition of dysregulated cell proliferation in proliferative retinopathies. This article is part of a Special Issue entitled 'Purines in Neurodegeneration and Neuroregeneration'. PMID:25998275

  2. Genetic pediatric retinal diseases

    PubMed Central

    Say, Emil Anthony T.

    2014-01-01

    Hereditary pediatric retinal diseases are a diverse group of disorders with pathologies affecting different cellular structures or retinal development. Many can mimic typical pediatric retinal disease such as retinopathy of prematurity, vitreous hemorrhage, retinal detachment and cystoid macular edema. Multisystem involvement is frequently seen in hereditary pediatric retinal disease. A thorough history coupled with a good physical examination can oftentimes lead the ophthalmologist or pediatrician to the correct genetic test and correct diagnosis. In some instances, evaluation of parents or siblings may be required to determine familial involvement when the history is inconclusive or insufficient and clinical suspicion is high.

  3. Delivery of neurotrophic factors and therapeutic proteins for retinal diseases.

    PubMed

    Thanos, Chris; Emerich, Dwaine

    2005-11-01

    Neurotrophic factors have the ability to protect and initiate growth of neurons. In the central nervous system, neurotrophic factors are neuroprotective in a wide range of disease states. Similarly, disease pathologies of the neurosensory retina respond favourably in animal models of retinitis pigmentosa, macular degeneration, glaucoma and others. With advances in drug delivery and cell therapy, an almost universal increase in efficacy is being realised. Now, repeated injections of neurotrophic factors are being replaced by controlled delivery of cell-mediated factor secretion, reducing the number of potential acute side effects. Tissue engineering strategies in conjunction with gene-modulated protein therapy or gene transfer are creating a unique treatment niche and are quickly gaining acclaim in the clinic. This review surveys the founding and current work on neurotrophic factors such as CNTF, BDNF, GDNF, LEDGF, PEDF and others. Ongoing clinical trials and successful preclinical studies are summarised as well. PMID:16255648

  4. Role of retinal metabolism in methanol-induced retinal toxicity

    SciTech Connect

    Garner, C.D. |; Lee, E.W.; Terzo, T.S.; Louis-Ferdinand, R.T.

    1995-08-01

    Methanol is a toxicant that causes systemic and ocular toxicity after acute exposure. The folate-reduced (FR) rat is an excellent animal model that mimics characteristic human methanol toxic responses. The present study examines the role of the methanol metabolites formaldehyde and formate in the initiation of methanol-induced retinal toxicity. After a single oral dose of 3.0 g/kg methanol, blood methanol concentrations were not significantly different in FR rats compared with folate-sufficient (FS) (control) rats. However, FR rats treated with 3.0 g/kg methanol displayed elevated blood (14.6 mM) and vitreous humor (19.5 mM) formate levels and abnormal electroretinograms (loss of b-wave) 48 h postdose. FR rats pretreated with disulfiram (DSF) prior to 3.0 g/kg methanol treatment failed to display these symptoms. Formaldehyde was not detected in blood or vitreous humor with or without DSF treatment, suggesting that formate is the toxic metabolite in methanol-induced retinal toxicity. Additionally, creating a blood formate profile (14.2 mM at 48 h) similar to that observed in methanol-treated rats by iv infusion of pH-buffered formate does not alter the electroretinogram as is observed with methanol treatment. These data suggest that intraretinal metabolism of methanol is necessary for the formate-mediated initiation of methanol-induced retinal toxicity. 31 refs., 5 figs., 2 tabs.

  5. N -methyl- N -nitrosourea-induced retinal degeneration in mice.

    PubMed

    Chen, Yuan-Yuan; Liu, Shi-Liang; Hu, Dan-Ping; Xing, Yi-Qiao; Shen, Yin

    2014-04-01

    Mouse retinal degeneration models have been investigated for many years in the hope of understanding the mechanism of photoreceptor cell death. N -methyl- N -nitrosourea (MNU) has been previously shown to induce outer retinal degeneration in mice. After MNU was intraperitoneally injected in C57/BL mice, we observed a gradual decrease in the outer nuclear layer (ONL) thickness associated with photoreceptor outer segment loss, bipolar cell dendritic retraction and reactive gliosis. Reactive gliosis was confirmed by increased GFAP protein levels. More serious damage to the central retina as opposed to the peripheral retina was found in the MNU-induced retinal degeneration model. Retinal ganglion cells (RGC) appear to be spared for at least two months after MNU treatment. Following retinal vessel labelling, we observed vascular complexes in the distal vessels, indicating retinal vessel damage. In the remnant retinal photoreceptor of the MNU-treated mouse, concentrated colouring nuclei were detected by electron microscopy, together with the loss of mitochondria and displaced remnant synaptic ribbons in the photoreceptor. We also observed decreased mitochondrial protein levels and increased amounts of nitrosylation/nitration in the photoreceptors. The mechanism of MNU-induced apoptosis may result from oxidative stress or the loss of retinal blood supply. MNU-induced mouse retinal degeneration in the outer retina is a useful animal model for photoreceptor degeneration diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). PMID:24509257

  6. The role of the immune system in central nervous system plasticity after acute injury.

    PubMed

    Peruzzotti-Jametti, L; Donegá, M; Giusto, E; Mallucci, G; Marchetti, B; Pluchino, S

    2014-12-26

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. PMID:24785677

  7. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    SciTech Connect

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J. )

    1990-10-15

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy.

  8. Simulated acute central Mycoplasma infections in rats induce fever, anorexia, body mass stunting and lethargy but spare memory.

    PubMed

    Swanepoel, Tanya; Sabbar, Mariam; Baartman, Tamzyn L; Laburn, Helen P; Mitchell, Duncan; Dukhan, Tanusha; Harden, Lois M

    2016-09-01

    Despite the documented post-infectious neurological complications of a central nervous system (CNS) Mycoplasma infection in humans, very few studies have investigated the acute inflammatory responses and sickness behaviours induced by CNS Mycoplasma infections. We therefore determined the effect of acute central administration of fibroblast-stimulating lipopeptide-1 (FSL-1), derived from Mycoplasma salivarium, and FAM-20 from a more pathogenic species, namely Mycoplasma pneumoniae, on behavioural and inflammatory responses in rats. Male Sprague-Dawley rats had radiotransmitters implanted, intra-abdominally, to measure body temperature and cage activity continuously. After recovery from surgery, rats were conditioned in a fear conditioning task and then immediately received an intra-cisterna magna (i.c.m.) injection of either: (1) FSL-1 (10 or 100μg/5μl) or its vehicle (phosphate-buffered saline, 5μl), or (2) FAM-20 (10 or 100μg/5μl) or its vehicle (dimethyl sulfoxide, 5μl). Body mass and food intake were measured daily. Memory was assessed seven days after injection using fear conditioning tests. A single, i.c.m. injection of either FSL-1 or FAM-20 induced profound, dose-dependent fever, anorexia, lethargy and body mass stunting in rats. Moreover, rats that received an i.c.m. injection of 100μg/5μl FAM-20 had a significant increase in the concentration of IL-1β in both the hypothalamus and the hippocampus for ~27h after injection. Seven days after FSL-1 or FAM-20 injection, when body mass of rats still was stunted, they maintained their memory for fear of the context and for fear of the tone, despite the increase in hippocampal IL-1β concentration after FAM-20 administration. Thus, acute simulated CNS Mycoplasma infections caused pronounced sickness responses and brain inflammation in rats, but spared fear memory. PMID:27180133

  9. Inferior retinal light exposure is more effective than superior retinal exposure in suppressing melatonin in humans

    NASA Technical Reports Server (NTRS)

    Glickman, Gena; Hanifin, John P.; Rollag, Mark D.; Wang, Jenny; Cooper, Howard; Brainard, George C.

    2003-01-01

    Illumination of different areas of the human retina elicits differences in acute light-induced suppression of melatonin. The aim of this study was to compare changes in plasma melatonin levels when light exposures of equal illuminance and equal photon dose were administered to superior, inferior, and full retinal fields. Nine healthy subjects participated in the study. Plexiglass eye shields were modified to permit selective exposure of the superior and inferior halves of the retinas of each subject. The Humphrey Visual Field Analyzer was used both to confirm intact full visual fields and to quantify exposure of upper and lower visual fields. On study nights, eyes were dilated, and subjects were exposed to patternless white light for 90 min between 0200 and 0330 under five conditions: (1) full retinal exposure at 200 lux, (2) full retinal exposure at 100 lux, (3) inferior retinal exposure at 200 lux, (4) superior retinal exposure at 200 lux, and (5) a dark-exposed control. Plasma melatonin levels were determined by radioimmunoassay. ANOVA demonstrated a significant effect of exposure condition (F = 5.91, p < 0.005). Post hoc Fisher PLSD tests showed significant (p < 0.05) melatonin suppression of both full retinal exposures as well as the inferior retinal exposure; however, superior retinal exposure was significantly less effective in suppressing melatonin. Furthermore, suppression with superior retinal exposure was not significantly different from that of the dark control condition. The results indicate that the inferior retina contributes more to the light-induced suppression of melatonin than the superior retina at the photon dosages tested in this study. Findings suggest a greater sensitivity or denser distribution of photoreceptors in the inferior retina are involved in light detection for the retinohypothalamic tract of humans.

  10. Central role of neutrophil in the pathogenesis of severe acute pancreatitis

    PubMed Central

    Yang, Zhi-wen; Meng, Xiao-xiao; Xu, Ping

    2015-01-01

    Severe acute pancreatitis (SAP) is an acute abdominal disease with the strong systemic inflammatory response, and rapidly progresses from a local pancreatic damage into multiple organ dysfunction. For many decades, the contributions of neutrophils to the pathology of SAP were traditionally thought to be the chemokine and cytokine cascades that accompany inflammation. In this review, we focus mainly on those recently recognized aspects of neutrophils in SAP processes. First, emerging evidence suggests that therapeutic interventions targeting neutrophils significantly lower tissue damage and protect against the occurrence of pancreatitis. Second, trypsin activation promotes the initial neutrophils recruitment into local pancreas, and subsequently neutrophils infiltration in turn triggers trypsin production. Finally, neutrophils have the unique ability to release neutrophil extracellular traps even in the absence of pathogens. PMID:26249268

  11. Central role of neutrophil in the pathogenesis of severe acute pancreatitis.

    PubMed

    Yang, Zhi-Wen; Meng, Xiao-Xiao; Xu, Ping

    2015-11-01

    Severe acute pancreatitis (SAP) is an acute abdominal disease with the strong systemic inflammatory response, and rapidly progresses from a local pancreatic damage into multiple organ dysfunction. For many decades, the contributions of neutrophils to the pathology of SAP were traditionally thought to be the chemokine and cytokine cascades that accompany inflammation. In this review, we focus mainly on those recently recognized aspects of neutrophils in SAP processes. First, emerging evidence suggests that therapeutic interventions targeting neutrophils significantly lower tissue damage and protect against the occurrence of pancreatitis. Second, trypsin activation promotes the initial neutrophils recruitment into local pancreas, and subsequently neutrophils infiltration in turn triggers trypsin production. Finally, neutrophils have the unique ability to release neutrophil extracellular traps even in the absence of pathogens. PMID:26249268

  12. Access to medicines for acute illness in middle income countries in Central America

    PubMed Central

    Emmerick, Isabel Cristina Martins; Luiza, Vera Lucia; Camacho, Luiz Antonio Bastos; Ross-Degnan, Dennis

    2013-01-01

    OBJECTIVE To analyze the main predictors of access to medicines for persons who experienced acute health conditions. METHODS This was a cross-sectional analytic study, based on data from household surveys. We examined the predictors of: (1) seeking care for acute illness in the formal health care system and (2) obtaining all medicines sought for the acute condition. RESULTS The significant predictors of seeking health care for acute illnesses were urban geographic location, head of household with secondary school education or above, age under 15, severity of illness perceived by the respondent, and having health insurance. The most important predictor of obtaining full access to medicines was seeking care in the formal health care system. People who sought care in the formal system were three times more likely to receive all the medicines sought (OR 3.0, 95%CI 2.3;4.0). For those who sought care in the formal health system, the strongest predictors of full access to medicines were seeking care in the private sector, having secondary school education or above, and positive perceptions of quality of health care and medicines in public sector health facilities. For patients who did not seek care in the formal health system, full access to medicines was more likely in Honduras or Nicaragua than in Guatemala. Urban geographic location, higher economic status, and male gender were also significant predictors. CONCLUSIONS A substantial part of the population in these three countries sought and obtained medicines outside of the formal health care system, which may compromise quality of care and pose a risk to patients. Determinants of full access to medicines inside and outside the formal health care system differ, and thus may require different strategies to improve access to medicines.  PMID:24626545

  13. A Novel Rhabdovirus Associated with Acute Hemorrhagic Fever in Central Africa

    PubMed Central

    Slikas, Elizabeth; Steffen, Imke; Muyembe, Jean-Jacques; Sittler, Taylor; Veeraraghavan, Narayanan; Ruby, J. Graham; Wang, Chunlin; Makuwa, Maria; Mulembakani, Prime; Tesh, Robert B.; Mazet, Jonna; Rimoin, Anne W.; Taylor, Travis; Schneider, Bradley S.; Simmons, Graham; Delwart, Eric; Wolfe, Nathan D.; Chiu, Charles Y.; Leroy, Eric M.

    2012-01-01

    Deep sequencing was used to discover a novel rhabdovirus (Bas-Congo virus, or BASV) associated with a 2009 outbreak of 3 human cases of acute hemorrhagic fever in Mangala village, Democratic Republic of Congo (DRC), Africa. The cases, presenting over a 3-week period, were characterized by abrupt disease onset, high fever, mucosal hemorrhage, and, in two patients, death within 3 days. BASV was detected in an acute serum sample from the lone survivor at a concentration of 1.09×106 RNA copies/mL, and 98.2% of the genome was subsequently de novo assembled from ∼140 million sequence reads. Phylogenetic analysis revealed that BASV is highly divergent and shares less than 34% amino acid identity with any other rhabdovirus. High convalescent neutralizing antibody titers of >1∶1000 were detected in the survivor and an asymptomatic nurse directly caring for him, both of whom were health care workers, suggesting the potential for human-to-human transmission of BASV. The natural animal reservoir host or arthropod vector and precise mode of transmission for the virus remain unclear. BASV is an emerging human pathogen associated with acute hemorrhagic fever in Africa. PMID:23028323

  14. Genetics Home Reference: retinitis pigmentosa

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions retinitis pigmentosa retinitis pigmentosa Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Retinitis pigmentosa is a group of related eye disorders that ...

  15. CCL5-glutamate interaction in central nervous system: Early and acute presynaptic defects in EAE mice.

    PubMed

    Di Prisco, Silvia; Merega, Elisa; Milanese, Marco; Summa, Maria; Casazza, Simona; Raffaghello, Lizzia; Pistoia, Vito; Uccelli, Antonio; Pittaluga, Anna

    2013-12-01

    We investigated the CCL5-glutamate interaction in the cortex and in the spinal cord from mice with Experimental Autoimmune Encephalomyelitis (EAE) at 13 and 21/30 days post immunization (d.p.i.), representing the onset and the peak of the disease, respectively. An early reduction of the KCl-evoked glutamate release was observed in cortical terminals from EAE mice at 13 d.p.i., persisting until 21/30 d.p.i. A concomitant reduction of the depolarization-evoked cyclic adenosine monophosphate (cAMP), but not of the inositol 1,4,5-trisphosphate (IP3) cortical production also occurred at 13 d.p.i, that still was detectable at the acute stage of disease (21 dp.i.). Inasmuch, the CCL5-mediated inhibition of glutamate exocytosis observed in control mice turned to facilitation in EAE mouse cortex at 13 d.p.i., then becoming undetectable at 21/30 d.p.i. Differently, glutamate exocytosis, as well as IP3 and cAMP productions were unaltered in spinal cord synaptosomes from EAE mice at 13 d.p.i., but significantly increased at 21/30 d.p.i., while the presynaptic CCL5-mediated facilitation of glutamate exocytosis observed in control mice remained unchanged. In both CNS regions, the presynaptic defects were parallelled by increased CCL5 availability. Inasmuch, the presynaptic defects so far described in EAE mice were reminiscent of the effects acute CCL5 exerts in control conditions. Based on these observations we propose that increased CCL5 bioavailability could have a role in determining the abovedescribed impaired presynaptic impairments in both CNS regions. These presynaptic defects could be relevant to the onset of early cognitive impairments and acute neuroinflammation and demyelinating processes observed in multiple sclerosis patients. PMID:23958452

  16. The retinal ciliopathies.

    PubMed

    Adams, N A; Awadein, Ahmed; Toma, Hassanain S

    2007-09-01

    While the functions of many of the proteins located in or associated with the photoreceptor cilia are poorly understood, disruption of the function of these proteins may result in a wide variety of phenotypes ranging from isolated retinal degeneration to more pleiotropic phenotypes. Systemic findings include neurosensory hearing loss, developmental delay, situs-inversus, infertility, disorders of limb and digit development, obesity, kidney disease, liver disease, and respiratory disease. The concept of "retinal ciliopathies" brings to attention the importance of further molecular analysis of this organelle as well as provides a potential common target for therapies for these disorders. The retinal ciliopathies include retinitis pigmentosa, macular degeneration, cone-dystrophy, cone-rod dystrophy, Leber congenital amaurosis, as well as retinal degenerations associated with Usher syndrome, primary ciliary dyskinesia, Senior-Loken syndrome, Joubert syndrome, Bardet-Biedl syndrome, Laurence-Moon syndrome, McKusick-Kaufman syndrome, and Biemond syndrome. Mutations for these disorders have been found in retinitis pigmentosa-1 (RP1), retinitis pigmentosa GTPase regulator (RPGR), retinitis pigmentosa GTPase regulator interacting protein (RPGR-IP), as well as the Usher, Bardet-Biedl, and nephronophthisis genes. Other systemic disorders associated with retinal degenerations that may also involve ciliary abnormalities include: Alstrom, Edwards-Sethi, Ellis-van Creveld, Jeune, Meckel-Gruber, Orofaciodigital Type 9, and Gurrieri syndromes. Understanding these conditions as ciliopathies may help the ophthalmologist to recognize associations between seemingly unrelated diseases and have a high degree of suspicion that a systemic finding may be present. PMID:17896309

  17. Central noradrenergic mechanisms and the acute stress response during painful stimulation.

    PubMed

    Chapman, C Richard; Bradshaw, David H; Donaldson, Gary W; Jacobson, Robert C; Nakamura, Yoshio

    2014-12-01

    Events that threaten tissue integrity including noxious stimulation activate central noradrenergic circuits, particularly locus coeruleus and its projections. Recent advances in theory hold that an adaptive, defensive shift in brain activity takes place in response to threat. In principle, this shift may accentuate the autonomic and central biomarkers of the perception of painful events and the experience of pain itself. We have examined the effects of an alpha-2 agonist on pupil dilation responses, skin conductance responses, near field somatosensory evoked potentials and pain reports in normal volunteers undergoing repeated trials of painful fingertip stimulation delivered at low, medium and high intensities. In a double-blinded study, 114 healthy male and female volunteers underwent repeated noxious stimulation under baseline, placebo and active drug conditions where the active drug was the alpha-2 agonist tizanidine 4 mg. In contrast to baseline and placebo conditions, tizanidine 4 mg significantly reduced the magnitudes of the mean pupil dilation response, the mean skin conductance response, the mean near field somatosensory evoked potential peak-to-peak amplitude and the mean pain intensity rating. Stimulus intensity significantly altered all three biomarkers and the pain report in a graded fashion. There were no sex differences. These findings support the hypotheses that painful events activate central noradrenergic circuits, and that these circuits play a role in the autonomic and central arousal associated with pain. PMID:25122041

  18. The central metabolism regulator EIIAGlc switches Salmonella from growth arrest to acute virulence through activation of virulence factor secretion.

    PubMed

    Mazé, Alain; Glatter, Timo; Bumann, Dirk

    2014-06-12

    The ability of Salmonella to cause disease depends on metabolic activities and virulence factors. Here, we show that a key metabolic protein, EIIAGlc, is absolutely essential for acute infection, but not for Salmonella survival, in a mouse typhoid fever model. Surprisingly, phosphorylation-dependent EIIAGlc functions, including carbohydrate transport and activation of adenylate cyclase for global regulation, do not explain this virulence phenotype. Instead, biochemical studies, in vitro secretion and translocation assays, and in vivo genetic epistasis experiments suggest that EIIAGlc binds to the type three secretion system 2 (TTSS-2) involved in systemic virulence, stabilizes its cytoplasmic part including the crucial TTSS-2 ATPase, and activates virulence factor secretion. This unexpected role of EIIAGlc reveals a striking direct link between central Salmonella metabolism and a crucial virulence mechanism. PMID:24835993

  19. Acute desipramine restores presynaptic cortical defects in murine experimental autoimmune encephalomyelitis by suppressing central CCL5 overproduction

    PubMed Central

    Di Prisco, Silvia; Merega, Elisa; Lanfranco, Massimiliano; Casazza, Simona; Uccelli, Antonio; Pittaluga, Anna

    2014-01-01

    Background and Purpose Altered glutamate exocytosis and cAMP production in cortical terminals of experimental autoimmune encephalomyelitis (EAE) mice occur at the early stage of disease (13 days post-immunization, d.p.i.). Neuronal defects were paralleled by overexpression of the central chemokine CCL5 (also known as RANTES), suggesting it has a role in presynaptic impairments. We propose that drugs able to restore CCL5 content to physiological levels could also restore presynaptic defects. Because of its efficacy in controlling CCL5 overexpression, desipramine (DMI) appeared to be a suitable candidate to test our hypothesis. Experimental Approach Control and EAE mice at 13 d.p.i. were acutely or chronically administered DMI and monitored for behaviour and clinical scores. Noradrenaline and glutamate release, cAMP, CCL5 and TNF-α production were quantified in cortical synaptosomes and homogenates. Peripheral cytokine production was also determined. Key Results Noradrenaline exocytosis and α2-adrenoeceptor-mediated activity were unmodified in EAE mice at 13 d.p.i. when compared with control. Acute, but not chronic, DMI reduced CCL5 levels in cortical homogenates of EAE mice at 13 d.p.i., but did not affect peripheral IL-17 and TNF-α contents or CCL5 plasma levels. Acute DMI caused a long-lasting restoration of glutamate exocytosis, restored endogenous cAMP production and impeded the shift from inhibition to facilitation of the CCL5-mediated control of glutamate exocytosis. Finally, DMI ameliorated anxiety-related behaviour but not motor activity or severity of clinical signs. Conclusions We propose DMI as an add-on therapy to normalize neuropsychiatric symptoms in multiple sclerosis patients at the early stage of the disease. PMID:24528439

  20. Effects of Centralizing Acute Stroke Services on Stroke Care Provision in Two Large Metropolitan Areas in England

    PubMed Central

    Morris, Stephen; Hoffman, Alex; Hunter, Rachael M.; Boaden, Ruth; McKevitt, Christopher; Perry, Catherine; Pursani, Nanik; Rudd, Anthony G.; Turner, Simon J.; Tyrrell, Pippa J.; Wolfe, Charles D.A.; Fulop, Naomi J.

    2015-01-01

    Background and Purpose— In 2010, Greater Manchester and London centralized acute stroke care into hyperacute units (Greater Manchester=3, London=8), with additional units providing ongoing specialist stroke care nearer patients’ homes. Greater Manchester patients presenting within 4 hours of symptom onset were eligible for hyperacute unit admission; all London patients were eligible. Research indicates that postcentralization, only London’s stroke mortality fell significantly more than elsewhere in England. This article attempts to explain this difference by analyzing how centralization affects provision of evidence-based clinical interventions. Methods— Controlled before and after analysis was conducted, using national audit data covering Greater Manchester, London, and a noncentralized urban comparator (38 623 adult stroke patients, April 2008 to December 2012). Likelihood of receiving all interventions measured reliably in pre- and postcentralization audits (brain scan; stroke unit admission; receiving antiplatelet; physiotherapist, nutrition, and swallow assessments) was calculated, adjusting for age, sex, stroke-type, consciousness, and whether stroke occurred in-hospital. Results— Postcentralization, likelihood of receiving interventions increased in all areas. London patients were overall significantly more likely to receive interventions, for example, brain scan within 3 hours: Greater Manchester=65.2% (95% confidence interval=64.3–66.2); London=72.1% (71.4–72.8); comparator=55.5% (54.8–56.3). Hyperacute units were significantly more likely to provide interventions, but fewer Greater Manchester patients were admitted to these (Greater Manchester=39%; London=93%). Differences resulted from contrasting hyperacute unit referral criteria and how reliably they were followed. Conclusions— Centralized systems admitting all stroke patients to hyperacute units, as in London, are significantly more likely to provide evidence-based clinical

  1. Intravital video microscopy measurements of retinal blood flow in mice.

    PubMed

    Harris, Norman R; Watts, Megan N; Leskova, Wendy

    2013-01-01

    Alterations in retinal blood flow can contribute to, or be a consequence of, ocular disease and visual dysfunction. Therefore, quantitation of altered perfusion can aid research into the mechanisms of retinal pathologies. Intravital video microscopy of fluorescent tracers can be used to measure vascular diameters and bloodstream velocities of the retinal vasculature, specifically the arterioles branching from the central retinal artery and of the venules leading into the central retinal vein. Blood flow rates can be calculated from the diameters and velocities, with the summation of arteriolar flow, and separately venular flow, providing values of total retinal blood flow. This paper and associated video describe the methods for applying this technique to mice, which includes 1) the preparation of the eye for intravital microscopy of the anesthetized animal, 2) the intravenous infusion of fluorescent microspheres to measure bloodstream velocity, 3) the intravenous infusion of a high molecular weight fluorescent dextran, to aid the microscopic visualization of the retinal microvasculature, 4) the use of a digital microscope camera to obtain videos of the perfused retina, and 5) the use of image processing software to analyze the video. The same techniques can be used for measuring retinal blood flow rates in rats. PMID:24429840

  2. Plasma Kallikrein Mediates Retinal Vascular Dysfunction and Induces Retinal Thickening in Diabetic Rats

    PubMed Central

    Clermont, Allen; Chilcote, Tamie J.; Kita, Takeshi; Liu, Jia; Riva, Priscilla; Sinha, Sukanto; Feener, Edward P.

    2011-01-01

    OBJECTIVE Plasma kallikrein (PK) has been identified in vitreous fluid obtained from individuals with diabetic retinopathy and has been implicated in contributing to retinal vascular dysfunction. In this report, we examined the effects of PK on retinal vascular functions and thickness in diabetic rats. RESEARCH DESIGN AND METHODS We investigated the effects of a selective PK inhibitor, ASP-440, and C1 inhibitor (C1-INH), the primary physiological inhibitor of PK, on retinal vascular permeability (RVP) and hemodynamics in rats with streptozotocin-induced diabetes. The effect of intravitreal PK injection on retinal thickness was examined by spectral domain optical coherence tomography. RESULTS Systemic continuous administration of ASP-440 for 4 weeks initiated at the time of diabetes onset inhibited RVP by 42% (P = 0.013) and 83% (P < 0.001) at doses of 0.25 and 0.6 mg/kg per day, respectively. Administration of ASP-440 initiated 2 weeks after the onset of diabetes ameliorated both RVP and retinal blood flow abnormalities in diabetic rats measured at 4 weeks’ diabetes duration. Intravitreal injection of C1-INH similarly decreased impaired RVP in rats with 2 weeks’ diabetes duration. Intravitreal injection of PK increased both acute RVP and sustained focal RVP (24 h postinjection) to a greater extent in diabetic rats compared with nondiabetic control rats. Intravitreal injection of PK increased retinal thickness compared with baseline to a greater extent (P = 0.017) in diabetic rats (from 193 ± 10 μm to 223 ± 13 μm) compared with nondiabetic rats (from 182 ± 8 μm to 193 ± 9 μm). CONCLUSIONS These results show that PK contributes to retinal vascular dysfunctions in diabetic rats and that the combination of diabetes and intravitreal injection of PK in rats induces retinal thickening. PMID:21444925

  3. Neonatal overfeeding attenuates acute central pro-inflammatory effects of short-term high fat diet

    PubMed Central

    Cai, Guohui; Dinan, Tara; Barwood, Joanne M.; De Luca, Simone N.; Soch, Alita; Ziko, Ilvana; Chan, Stanley M. H.; Zeng, Xiao-Yi; Li, Songpei; Molero, Juan; Spencer, Sarah J.

    2015-01-01

    Neonatal obesity predisposes individuals to obesity throughout life. In rats, neonatal overfeeding also leads to early accelerated weight gain that persists into adulthood. The phenotype is associated with dysfunction in a number of systems including paraventricular nucleus of the hypothalamus (PVN) responses to psychological and immune stressors. However, in many cases weight gain in neonatally overfed rats stabilizes in early adulthood so the animal does not become more obese as it ages. Here we examined if neonatal overfeeding by suckling rats in small litters predisposes them to exacerbated metabolic and central inflammatory disturbances if they are also given a high fat diet in later life. In adulthood we gave the rats normal chow, 3 days, or 3 weeks high fat diet (45% kcal from fat) and measured peripheral indices of metabolic disturbance. We also investigated hypothalamic microglial changes, as an index of central inflammation, as well as PVN responses to lipopolysaccharide (LPS). Surprisingly, neonatal overfeeding did not predispose rats to the metabolic effects of a high fat diet. Weight changes and glucose metabolism were unaffected by the early life experience. However, short term (3 day) high fat diet was associated with more microglia in the hypothalamus and a markedly exacerbated PVN response to LPS in control rats; effects not seen in the neonatally overfed. Our findings indicate neonatally overfed animals are not more susceptible to the adverse metabolic effects of a short-term high fat diet but may be less able to respond to the central effects. PMID:25628527

  4. Acute low-level microwave exposure and central cholinergic activity: studies on irradiation parameters

    SciTech Connect

    Lai, H.; Horita, A.; Guy, A.W.

    1988-01-01

    Sodium-dependent high-affinity choline uptake was measured in the striatum, frontal cortex, hippocampus, and hypothalamus of rats after acute exposure (45 min) to pulsed (2 microseconds, 500 pps) or continuous-wave 2,450-MHz microwaves in cylindrical waveguides or miniature anechoic chambers. In all exposure conditions, the average whole-body specific absorption rate was at 0.6 W/kg. Decrease in choline uptake was observed in the frontal cortex after microwave exposure in all of the above irradiation conditions. Regardless of the exposure system used, hippocampal choline uptake was decreased after exposure to pulsed but not continuous-wave microwaves. Striatal choline uptake was decreased after exposure to either pulsed or continuous-wave microwaves in the miniature anechoic chamber. No significant change in hypothalamic choline uptake was observed under any of the exposure conditions studied. We conclude that depending on the parameters of the radiation, microwaves can elicit specific and generalized biological effects.

  5. Central nervous system involvement at first relapse in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline monochemotherapy without intrathecal prophylaxis

    PubMed Central

    Montesinos, Pau; Díaz-Mediavilla, Joaquín; Debén, Guillermo; Prates, Virginia; Tormo, Mar; Rubio, Vicente; Pérez, Inmaculada; Fernández, Isolda; Viguria, Maricruz; Rayón, Chelo; González, José; de la Serna, Javier; Esteve, Jordi; Bergua, Juan M.; Rivas, Concha; González, Marcos; González, Jose D.; Negri, Silvia; Brunet, Salut; Lowenberg, Bob; Sanz, Miguel A.

    2009-01-01

    Background The prevalence of and risk factors for central nervous system recurrence in patients with acute promyelocytic leukemia are not well established and remain a controversial matter. Design and Methods Between 1996 and 2005, 739 patients with newly diagnosed acute promyelocytic leukemia enrolled in two consecutive trials (PETHEMA LPA96 and LPA99) received induction therapy with all-trans retinoic acid and idarubicin. Consolidation therapy comprised three courses of anthracycline monochemotherapy (LPA96), with all-trans retinoic acid and reinforced doses of idarubicin in patients with an intermediate or high risk of relapse (LPA99). Central nervous system prophylaxis was not given. Results Central nervous system relapse was documented in 11 patients. The 5-year cumulative incidence of central nervous system relapse was 1.7% (LPA96 3.2% and LPA99 1.2%; p=0.09). The cumulative incidence was 0%, 0.8%, and 5.5% in low-, intermediate-, and high-risk patients, respectively. Relapse risk score (p=0.0001) and the occurrence of central nervous system hemorrhage during induction (5-year cumulative incidence 18.7%, p=0.006) were independent risk factors for central nervous system relapse. Conclusions This study shows a low incidence of central nervous system relapse in patients with acute promyelocytic leukemia following therapy with all-trans retinoic acid and anthracycline without specific central nervous system prophylaxis. Central nervous system relapse was significantly associated with high white blood cell counts and prior central nervous system hemorrhage, which emerged as independent prognostic factors. PMID:19608685

  6. A case of central nervous system relapse in acute promyelocytic leukemia.

    PubMed

    Hasuike, Yuhei; Yamaguchi, Hiroshi; Mitsui, Hideki; Nishikawa, Yoshiro; Sugai, Fuminobu

    2016-04-28

    A 70-year-old woman who have achieved complete remission (CR) of acute promyelocytic leukemia (APL) with all-trans retinoic acid and chemotherapy presented with abnormal sensation in the right lateral thigh and the bilateral legs. In addition, neurological examination revealed weakness of the left shoulder abduction, the right hand, and the bilateral lower limbs. Atypical promyelocytes were detected in the cerebrospinal fluid, in spite of normal finding in the peripheral blood smear. Magnetic resonance imaging showed gadolinium-enhanced multiple intradural/extramedullary lesions in the whole spine. Nerve conduction studies of the right limbs revealed sensorimotor conduction abnormalities, conspicuously in the posterior tibial and sural nerves. As a result, she was diagnosed as having intrathecal relapse of APL, associated with multiple mononeuropathy. The neurological symptoms were completely disappeared by intrathecal chemotherapy and whole-spine radiotherapy, suggesting that the neuropathy was possibly caused by meningeal infiltration affecting multiple spinal nerve roots. Since extramedullary or intrathecal relapse is extremely rare in APL compared with other types of leukemia, precise neurological evaluations and suitable treatment should be performed immediately, when APL patients with CR manifest some neurological symptoms. PMID:27025992

  7. Improvement of central visual function following steroid pulse therapy in acute zonal occult outer retinopathy.

    PubMed

    Kitakawa, Takaaki; Hayashi, Takaaki; Takashina, Hirotsugu; Mitooka, Katsuya; Gekka, Tamaki; Tsuneoka, Hiroshi

    2012-06-01

    The purpose of this study was to report a patient with acute zonal occult outer retinopathy (AZOOR) unilaterally, who received steroid pulse therapy. A 42-year-old woman presented with photopsias and severe vision loss in her left eye. Visual acuity was 0.04, and Humphrey visual field testing showed overall depression with a mean deviation (MD) value of -25.78 dB in the left eye. Fundus and angiographic examinations found no specific abnormal findings, leading to a diagnosis of AZOOR. Optical coherence tomography showed attenuation of the photoreceptor inner segment/outer segment junction (IS/OS) line. Focal macular electroretinography (fmERG) demonstrated that there were non-detectable responses at 5°, 10° and 15° (in diameter). Following steroid pulse therapy, her visual acuity was 1.0, her MD value improved to -16.08 dB, and there were both partial recovery of the IS/OS line and apparent improvements of fmERG responses (at 10° and 15°). The present findings suggest that steroid pulse therapy might potentially be an effective treatment in some AZOOR patients. PMID:22402912

  8. Primary Vitreoretinal Lymphoma Masquerading as Refractory Retinitis

    PubMed Central

    Zloto, Ofira; Elkader, Amir E. Abd; Fabian, Ido Didi; Vishnevskia-Dai, Vicktoria

    2015-01-01

    Purpose To report a case of a patient with primary vitreoretinal lymphoma masquerading as retinitis. Methods Retrospective review of the patient's clinical, histopathological and imaging records. Results Cytopathology was negative for malignancy, and preliminary polymerase chain reaction results supported the diagnosis of varicella zoster virus retinitis. Therefore, the patient was treated with antiviral therapy. However, under this treatment, the retinitis progressed. As a result, primary vitreoretinal lymphoma was suspected, and empirical treatment with intravitreal methotrexate injections was started. Under this treatment, the ocular features improved. Five months after initial ocular presentation and ocular resolution, the patient presented with central nervous system lymphoma. Conclusion This case should raise the awareness of the variable clinical presentations, the challenging diagnosis and treatment of primary vitreoretinal lymphoma. All cases should be continuously systemically evaluated. PMID:26557084

  9. Integrated computer-aided retinal photocoagulation system

    NASA Astrophysics Data System (ADS)

    Barrett, Steven F.; Wright, Cameron H. G.; Oberg, Erik D.; Rockwell, Benjamin A.; Cain, Clarence P.; Jerath, Maya R.; Rylander, Henry G., III; Welch, Ashley J.

    1996-05-01

    Successful retinal tracking subsystem testing results in vivo on rhesus monkeys using an argon continuous wave laser and an ultra-short pulse laser are presented. Progress on developing an integrated robotic retinal laser surgery system is also presented. Several interesting areas of study have developed: (1) 'doughnut' shaped lesions that occur under certain combinations of laser power, spot size, and irradiation time complicating measurements of central lesion reflectance, (2) the optimal retinal field of view to achieve simultaneous tracking and lesion parameter control, and (3) a fully digital versus a hybrid analog/digital tracker using confocal reflectometry integrated system implementation. These areas are investigated in detail in this paper. The hybrid system warrants a separate presentation and appears in another paper at this conference.

  10. Laser-induced retinal damage thresholds for annular retinal beam profiles

    NASA Astrophysics Data System (ADS)

    Kennedy, Paul K.; Zuclich, Joseph A.; Lund, David J.; Edsall, Peter R.; Till, Stephen; Stuck, Bruce E.; Hollins, Richard C.

    2004-07-01

    The dependence of retinal damage thresholds on laser spot size, for annular retinal beam profiles, was measured in vivo for 3 μs, 590 nm pulses from a flashlamp-pumped dye laser. Minimum Visible Lesion (MVL)ED50 thresholds in rhesus were measured for annular retinal beam profiles covering 5, 10, and 20 mrad of visual field; which correspond to outer beam diameters of roughly 70, 160, and 300 μm, respectively, on the primate retina. Annular beam profiles at the retinal plane were achieved using a telescopic imaging system, with the focal properties of the eye represented as an equivalent thin lens, and all annular beam profiles had a 37% central obscuration. As a check on experimental data, theoretical MVL-ED50 thresholds for annular beam exposures were calculated using the Thompson-Gerstman granular model of laser-induced thermal damage to the retina. Threshold calculations were performed for the three experimental beam diameters and for an intermediate case with an outer beam diameter of 230 μm. Results indicate that the threshold vs. spot size trends, for annular beams, are similar to the trends for top hat beams determined in a previous study; i.e., the threshold dose varies with the retinal image area for larger image sizes. The model correctly predicts the threshold vs. spot size trends seen in the biological data, for both annular and top hat retinal beam profiles.

  11. Classification of left and right eye retinal images

    NASA Astrophysics Data System (ADS)

    Tan, Ngan Meng; Liu, Jiang; Wong, Damon W. K.; Zhang, Zhuo; Lu, Shijian; Lim, Joo Hwee; Li, Huiqi; Wong, Tien Yin

    2010-03-01

    Retinal image analysis is used by clinicians to diagnose and identify, if any, pathologies present in a patient's eye. The developments and applications of computer-aided diagnosis (CAD) systems in medical imaging have been rapidly increasing over the years. In this paper, we propose a system to classify left and right eye retinal images automatically. This paper describes our two-pronged approach to classify left and right retinal images by using the position of the central retinal vessel within the optic disc, and by the location of the macula with respect to the optic nerve head. We present a framework to automatically identify the locations of the key anatomical structures of the eye- macula, optic disc, central retinal vessels within the optic disc and the ISNT regions. A SVM model for left and right eye retinal image classification is trained based on the features from the detection and segmentation. An advantage of this is that other image processing algorithms can be focused on regions where diseases or pathologies and more likely to occur, thereby increasing the efficiency and accuracy of the retinal CAD system/pathology detection. We have tested our system on 102 retinal images, consisting of 51 left and right images each and achieved and accuracy of 94.1176%. The high experimental accuracy and robustness of this system demonstrates that there is potential for this system to be integrated and applied with other retinal CAD system, such as ARGALI, for a priori information in automatic mass screening and diagnosis of retinal diseases.

  12. Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin

    SciTech Connect

    Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice

    2011-06-10

    Highlights: {yields} Toxicological implications associated with the use of NaNO{sub 2} therapy to treat systemic cell-free Hb exposure are not well-defined. {yields} Systemic Hb exposure followed by NaNO{sub 2} infusion induces acute CNS toxicities in guinea pigs. {yields} These CNS effects were not reproduced by the infusion of cell-free Hb or NaNO{sub 2} alone. {yields} NaNO{sub 2}-mediated oxidation of cell-free Hb may play a causative role in the observed CNS changes. -- Abstract: Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO{sub 2}) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO{sub 2} with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO{sub 2} on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO{sub 2}, at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO{sub 2} alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity.

  13. Differential Diagnosis of Retinal Vasculitis

    PubMed Central

    Abu El-Asrar, Ahmed M.; Herbort, Carl P.; Tabbara, Khalid F.

    2009-01-01

    Retinal vaculitis is a sight-threatening inflammatory eye condition that involves the retinal vessels. Detection of retinal vasculitis is made clinically, and confirmed with the help of fundus fluorescein angiography. Active vascular disease is characterized by exudates around retinal vessels resulting in white sheathing or cuffing of the affected vessels. In this review, a practical approach to the diagnosis of retinal vasculitis is discussed based on ophthalmoscopic and fundus fluorescein angiographic findings. PMID:20404987

  14. Negative Energy Balance Blocks Neural and Behavioral Responses to Acute Stress by “Silencing” Central Glucagon-Like Peptide 1 Signaling in Rats

    PubMed Central

    Maniscalco, James W.; Zheng, Huiyuan; Gordon, Patrick J.

    2015-01-01

    Previous reports indicate that caloric restriction attenuates anxiety and other behavioral responses to acute stress, and blunts the ability of stress to increase anterior pituitary release of adrenocorticotropic hormone. Since hindbrain glucagon-like peptide-1 (GLP-1) neurons and noradrenergic prolactin-releasing peptide (PrRP) neurons participate in behavioral and endocrine stress responses, and are sensitive to the metabolic state, we examined whether overnight food deprivation blunts stress-induced recruitment of these neurons and their downstream hypothalamic and limbic forebrain targets. A single overnight fast reduced anxiety-like behavior assessed in the elevated-plus maze and acoustic startle test, including marked attenuation of light-enhanced startle. Acute stress [i.e., 30 min restraint (RES) or 5 min elevated platform exposure] robustly activated c-Fos in GLP-1 and PrRP neurons in fed rats, but not in fasted rats. Fasting also significantly blunted the ability of acute stress to activate c-Fos expression within the anterior ventrolateral bed nucleus of the stria terminalis (vlBST). Acute RES stress suppressed dark-onset food intake in rats that were fed ad libitum, whereas central infusion of a GLP-1 receptor antagonist blocked RES-induced hypophagia, and reduced the ability of RES to activate PrRP and anterior vlBST neurons in ad libitum-fed rats. Thus, an overnight fast “silences” GLP-1 and PrRP neurons, and reduces both anxiety-like and hypophagic responses to acute stress. The partial mimicking of these fasting-induced effects in ad libitum-fed rats after GLP-1 receptor antagonism suggests a potential mechanism by which short-term negative energy balance attenuates neuroendocrine and behavioral responses to acute stress. SIGNIFICANCE STATEMENT The results from this study reveal a potential central mechanism for the “metabolic tuning” of stress responsiveness. A single overnight fast, which markedly reduces anxiety-like behavior in rats

  15. Retinal oximeter for the blue-green oximetry technique

    NASA Astrophysics Data System (ADS)

    Denninghoff, Kurt R.; Sieluzycka, Katarzyna B.; Hendryx, Jennifer K.; Ririe, Tyson J.; Deluca, Lawrence; Chipman, Russell A.

    2011-10-01

    Retinal oximetry offers potential for noninvasive assessment of central venous oxyhemoglobin saturation (SO2) via the retinal vessels but requires a calibrated accuracy of +/-3% saturation in order to be clinically useful. Prior oximeter designs have been hampered by poor saturation calibration accuracy. We demonstrate that the blue-green oximetry (BGO) technique can provide accuracy within +/-3% in swine when multiply scattered light from blood within a retinal vessel is isolated. A noninvasive on-axis scanning retinal oximeter (ROx-3) is constructed that generates a multiwavelength image in the range required for BGO. A field stop in the detection pathway is used in conjunction with an anticonfocal bisecting wire to remove specular vessel reflections and isolate multiply backscattered light from the blood column within a retinal vessel. This design is tested on an enucleated swine eye vessel and a retinal vein in a human volunteer with retinal SO2 measurements of ~1 and ~65%, respectively. These saturations, calculated using the calibration line from earlier work, are internally consistent with a standard error of the mean of +/-2% SO2. The absolute measures are well within the expected saturation range for the site (-1 and 63%). This is the first demonstration of noninvasive on-axis BGO retinal oximetry.

  16. Relationship between retinal vascular occlusions and incident cerebrovascular diseases

    PubMed Central

    Zhou, Yue; Zhu, Wengen; Wang, Changyun

    2016-01-01

    Abstract Several studies investigating the role of retinal vascular occlusions, on cerebrovascular diseases (CVD) have been reported, but the results are still inconsistent. We therefore sought to evaluate the relationship between retinal vascular occlusions and CVD. We systematically searched the Cochrane Library, PubMed, and ScienceDirect databases through January 31, 2016 for studies evaluating the effect of retinal vascular occlusions on the risk of CVD. Data were abstracted using predefined criteria, and then pooled by RevMan 5.3 software. A total of 9 retrospective studies were included in this meta-analysis. When compared with individuals without retinal vascular occlusions, both individuals with retinal artery occlusion (RAO) (odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.21–3.34; P = 0.005) and individuals with retinal vein occlusion (RVO) (OR = 1.37, 95% CI: 1.24–1.50; P < 0.00001) had higher risks of developing CVD. Additionally, both individuals with central retinal artery occlusion (CRAO) (OR = 2.00, 95% CI: 1.12–3.56; P = 0.02) and branch retinal artery occlusion (BRAO) (OR = 1.60, 95% CI: 1.03–1.48; P = 0.04) were significantly associated with increased risk of CVD. Published literatures support both RVO and RAO are associated with increased risks of CVD. Further prospective studies are needed to confirm these findings. PMID:27368050

  17. Acute Cerebrovascular Radiation Syndrome: Radiation Neurotoxicity , mechanisms of CNS radiation injury, advanced countermeasures for Radiation Protection of Central Nervous System.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Jones, Jeffrey; Maliev, Slava

    Key words: Cerebrovascular Acute Radiation Syndrome (Cv ARS), Radiation Neurotoxins (RNT), Neurotransmitters, Radiation Countermeasures, Antiradiation Vaccine (ArV), Antiradiation Blocking Antibodies, Antiradiation Antidote. Psychoneuroimmunology, Neurotoxicity. ABSTRACT: To review the role of Radiation Neurotoxins in triggering, developing of radiation induced central nervous system injury. Radiation Neurotoxins - rapidly acting blood toxic lethal agent, which activated after irradiation and concentrated, circulated in interstitial fluid, lymph, blood with interactions with cell membranes, receptors and cell compartments. Radiation Neurotoxins - biological molecules with high enzymatic activity and/or specific lipids and activated or modified after irradiation. The Radiation Neurotoxins induce increased permeability of blood vessels, disruption of the blood-brain barrier, blood-cerebrospinal fluid (CSF) barrier and developing severe disorder of blood macro- and micro-circulation. Principles of Radiation Psychoneuro-immunology and Psychoneuro-allergology were applied for determination of pathological processes developed after irradiation or selective administration of Radiation Neurotoxins to radiation naïve mammals. Effects of radiation and exposure to radiation can develop severe irreversible abnormalities of Central Nervous System, brain structures and functions. Antiradiation Vaccine - most effective, advanced methods of protection, prevention, mitigation and treatment and was used for of Acute Radiation Syndromes and elaboration of new technology for immune-prophylaxis and immune-protection against ϒ, Heavy Ion, Neutron irradiation. Results of experiments suggested that blocking, antitoxic, antiradiation antibodies can significantly reduce toxicity of Radiation Toxins. New advanced technology include active immune-prophylaxis with Antiradiation Vaccine and Antiradiation therapy that included specific blocking antibodies to Radiation Neurotoxins

  18. Retinal vascular regeneration.

    PubMed

    Otani, Atsushi; Friedlander, Martin

    2005-01-01

    We discuss the potential use of stem cells for therapeutic angiogenesis in the treatment of retinal diseases. We demonstrate that the clinical utility of these EPC may be not limited in the treatment of ischemic retinal diseases but may also have application for the treatment of retinal degenerative disorders and for a form of cell-based gene therapy. One of the greatest potential benefits of bone marrow derived EPC therapy is the possible use of autologous grafts. Nonetheless, potential toxicities and unregulated cell growth will need to be carefully evaluated before this approach is brought to the clinics. PMID:15804843

  19. Melanopsin-expressing intrinsically photosensitive retinal ganglion cells in retinal disease.

    PubMed

    Feigl, Beatrix; Zele, Andrew J

    2014-08-01

    Melanopsin-containing intrinsically photosensitive retinal ganglion cells (ipRGCs) are a class of photoreceptors with established roles in non-image-forming processes. Their contributions to image-forming vision may include the estimation of brightness. Animal models have been central for understanding the physiological mechanisms of ipRGC function and there is evidence of conservation of function across species. Intrinsically photosensitive retinal ganglion cells can be divided into five ganglion cell subtypes that show morphological and functional diversity. Research in humans has established that ipRGCs signal environmental irradiance to entrain the central body clock to the solar day for regulating circadian processes and sleep. In addition, ipRGCs mediate the pupil light reflex (PLR), making the PLR a readily accessible behavioral marker of ipRGC activity. Less is known about ipRGC function in retinal and optic nerve disease, with emerging research providing insight into their function in diabetes, retinitis pigmentosa, glaucoma, and hereditary optic neuropathy. We briefly review the anatomical distributions, projections, and basic physiological mechanisms of ipRGCs and their proposed and known functions in animals and humans with and without eye disease. We introduce a paradigm for differentiating inner and outer retinal inputs to the pupillary control pathway in retinal disease and apply this paradigm to patients with age-related macular degeneration (AMD). In these cases of patients with AMD, we provide the initial evidence that ipRGC function is altered and that the dysfunction is more pronounced in advanced disease. Our perspective is that with refined pupillometry paradigms, the PLR can be extended to AMD assessment as a tool for the measurement of inner and outer retinal dysfunction. PMID:24879087

  20. Inner retinal change in a novel rd1-FTL mouse model of retinal degeneration

    PubMed Central

    Greferath, Ursula; Anderson, Emily E.; Jobling, Andrew I.; Vessey, Kirstan A.; Martinez, Gemma; de Iongh, Robb U.; Kalloniatis, Michael; Fletcher, Erica L.

    2015-01-01

    While photoreceptor loss is the most devastating result of inherited retinal degenerations such as retinitis pigmentosa, inner retinal neurons also undergo significant alteration. Detailing these changes has become important as many vision restorative therapies target the remaining neurons. In this study, the rd1-Fos-Tau-LacZ (rd1-FTL) mouse model was used to explore inner retinal change at a late stage of retinal degeneration, after the loss of photoreceptor nuclei. The rd1-FTL model carries a mutation in the phosphodiesterase gene, Pde6b, and an axonally targeted transgenic beta galactosidase reporter system under the control of the c-fos promoter. Retinae of transgenic rd1-FTL mice and control FTL animals aged 2–12 months were processed for indirect fluorescence immunocytochemistry. At 2 months of age, a time when the majority of photoreceptor nuclei are lost, there was negligible c-fos reporter (FTL) expression, however, from 4 months, reporter expression was observed to increase within subpopulations of amacrine and ganglion cells within the central retina. These areas of inner retinal FTL expression coincided with regions that contained aberrant Müller cells. Specifically, these cells exhibited reduced glutamine synthetase and Kir4.1 immunolabelling, whilst showing evidence of proliferative gliosis (increased cyclinD1 and glial fibrillary acidic protein expression). These changes were limited to distinct regions where cone photoreceptor terminals were absent. Overall, these results highlight that distinct areas of the rd1-FTL central retina undergo significant glial alterations after cone photoreceptor loss. These areas coincide with up-regulation of the c-fos reporter in the inner retina, which may represent a change in neuronal function/plasticity. The rd1-FTL mouse is a useful model system to probe changes that occur in the inner retina at later stages of retinal degeneration. PMID:26283925

  1. Changes in morphology of retinal ganglion cells with eccentricity in retinal degeneration.

    PubMed

    Anderson, E E; Greferath, U; Fletcher, E L

    2016-05-01

    Ganglion cells are the output neurons of the retina and are known to remodel during the subtle plasticity changes that occur following the death of photoreceptors in inherited retinal degeneration. We examine the influence of retinal eccentricity on anatomical remodelling and ganglion cell morphology well after photoreceptor loss. Rd1 mice that have a mutation in the β subunit of phosphodiesterase 6 were used as a model of retinal degeneration and gross remodelling events were examined by processing serial sections for immunocytochemistry. Retinal wholemounts from rd1-Thy1 and control Thy1 mice that contained a fluorescent protein labelling a subset of ganglion cells were processed for immunohistochemistry at 11 months of age. Ganglion cells were classified based on their soma size, dendritic field size and dendritic branching pattern and their dendritic fields were analysed for their length, area and quantity of branching points. Overall, more remodelling was found in the central compared with the peripheral retina. In addition, the size and complexity of A2, B1, C1 and D type ganglion cells located in the central region of the retina decreased. We propose that the changes in ganglion cell morphology are correlated with remodelling events in these regions and impact the function of retinal circuitry in the degenerated retina. PMID:26670589

  2. Retinal artery-vein caliber grading using color fundus imaging.

    PubMed

    Bhuiyan, Alauddin; Kawasaki, Ryo; Lamoureux, Ecosse; Ramamohanarao, Kotagiri; Wong, Tien Yin

    2013-07-01

    Recent research suggests that retinal vessel caliber (or cross-sectional width) measured from retinal photographs is an important feature for predicting cardiovascular diseases (CVDs). One of the most utilized measures is to quantify retinal arteriolar and venular caliber as the Central Retinal Artery Equivalent (CRAE) and Central Retinal Vein Equivalent (CRVE). However, current computer tools utilize manual or semi-automatic grading methods to estimate CRAE and CRVE. These methods involve a significant amount of grader's time and can add a significant level of inaccuracy due to repetitive nature of grading and intragrader distances. An automatic and time efficient grading of the vessel caliber with highly repeatable measurement is essential, but is technically challenging due to a substantial variation of the retinal blood vessels' properties. In this paper, we propose a new technique to measure the retinal vessel caliber, which is an "edge-based" vessel tracking method. We measured CRAE and CRVE from each of the vessel types. We achieve very high accuracy (average 96.23%) for each of the cross-sectional width measurement compared to manually graded width. For overall vessel caliber measurement accuracy of CRAE and CRVE, we compared the results with an existing semi-automatic method which showed high correlation of 0.85 and 0.92, respectively. The intra-grader reproducibility of our method was high, with the correlation coefficient of 0.881 for CRAE and 0.875 for CRVE. PMID:23535181

  3. Reprogramming of adult rod photoreceptors prevents retinal degeneration

    PubMed Central

    Montana, Cynthia L.; Kolesnikov, Alexander V.; Shen, Susan Q.; Myers, Connie A.; Kefalov, Vladimir J.; Corbo, Joseph C.

    2013-01-01

    A prime goal of regenerative medicine is to direct cell fates in a therapeutically useful manner. Retinitis pigmentosa is one of the most common degenerative diseases of the eye and is associated with early rod photoreceptor death followed by secondary cone degeneration. We hypothesized that converting adult rods into cones, via knockdown of the rod photoreceptor determinant Nrl, could make the cells resistant to the effects of mutations in rod-specific genes, thereby preventing secondary cone loss. To test this idea, we engineered a tamoxifen-inducible allele of Nrl to acutely inactivate the gene in adult rods. This manipulation resulted in reprogramming of rods into cells with a variety of cone-like molecular, histologic, and functional properties. Moreover, reprogramming of adult rods achieved cellular and functional rescue of retinal degeneration in a mouse model of retinitis pigmentosa. These findings suggest that elimination of Nrl in adult rods may represent a unique therapy for retinal degeneration. PMID:23319618

  4. Retinal vein occlusion

    MedlinePlus

    ... Berrocal MH, Rodriguez FJ, et al. Pan-American Collaborative Retina Study Group (PACORES). Comparison of two doses ... retinal vein occlusion: results from the Pan-American Collaborative Retina Study Group at 6 months of follow- ...

  5. Iatrogenic acute cardiac tamponade during percutaneous removal of a fractured peripherally inserted central catheter in a premature neonate.

    PubMed

    Minghui, Zou; Hujun, Cui; Li, Ma; Weidan, Chen; Yanqin, Cui; Xinxin, Chen

    2015-01-01

    Acute cardiac tamponade (ACT) is a life-threatening complication associated with a peripherally inserted central catheter (PICC) in premature neonates. We present a case of ACT in a 4-day-old male infant. On the second admission day, a PICC was inserted. After 2.5 months, chest radiography showed PICC fracture, and its distal portion had migrated into the right pulmonary artery. Percutaneous removal through cardiac catheterization was attempted. However, right ventriculography demonstrated intrapericardial spillage of contrast agents, and iatrogenic ACT was confirmed. Cardiopulmonary resuscitation (CPR) was immediately started with open-chest cardiac massage. Further surgical exploration revealed right atrial appendage perforation. After 25-min CPR, the patient restored spontaneous circulation, and removal of the foreign bodies was performed. The post-operative course was uneventful. PICC fracture is an uncommon complication, but may be life-threatening. Precaution should be taken to avoid ACT during removal of a broken PICC. Once the tamponade is diagnosed, immediate interventions are mandatory. PMID:26105562

  6. Immediate and long-term posttherapy neuropsychologic performance in children with acute lymphoblastic leukemia treated without central nervous system radiation.

    PubMed

    Tamaroff, M; Miller, D R; Murphy, M L; Salwen, R; Ghavimi, F; Nir, Y

    1982-10-01

    Intellectual and neuropsychologic test performance was studied in 41 children with acute lymphoblastic leukemia within one year of completing multidrug therapy in which intrathecal methotrexate was the sole agent of central nervous system prophylaxis. To control for possible effects of intensive systemic chemotherapy and the disruptive psychosocial effects of treatment on psychometric test function, 33 children with embryonal rhabdomyosarcoma who had no CNS disease or treatment were similarly studied. All patients studied had been in continuous complete remission since diagnosis. Within each diagnostic group, patients were placed in a younger (less than 8 years) or an older (more than 8 years) group depending on age at the time of testing. No significant difference was found in intellectual function between the young ALL and ERMS groups or between the total ALL and ERMS groups. Further five-year follow-up of 12 of the youngest ALL patients showed no significant long-term change in intellectual or other specific neuropsychologic functions. Children with ALL who remained in continuous complete remission from diagnosis and who were treated with prophylactic intrathecal methotrexate and no CNS radiation did not have global or specific neuropsychologic impairment. PMID:6956704

  7. Retinal detachment in pseudophakia.

    PubMed

    Galin, M A; Poole, T A; Obstbaum, S A

    1979-07-01

    In a series of cataract patients excluding myopic individuals, under age 60 years, and cases in which vitreous loss occurred, retinal detachment was no less frequent after intracapsular cataract extraction and Sputnik iris supported lenses than in controls. Both groups were followed up for a minimum of two years. The detachments predominantly occurred from retinal breaks in areas of the retina that looked normal preoperatively. PMID:464014

  8. A novel method for detection of preferred retinal locus (PRL) through simple retinal image processing using MATLAB

    NASA Astrophysics Data System (ADS)

    Kalikivayi, V.; Pal, Sudip; Ganesan, A. R.

    2013-09-01

    simple and new technique for detection of `Preferred Retinal Locus' (PRL) in human eye is proposed in this paper. Simple MATLAB algorithms for estimating RGB pixel intensity values of retinal images were used. The technique proved non-existence of `S' cones in Fovea Centralis and also proposes that rods are involved in blue color perception. Retinal images of central vision loss and normal retina were taken for image processing. Blue minimum, Red maximum and Red+Green maximum were the three methods used in detecting PRL. Comparative analyses were also performed for these methods with patient's age and visual acuity.

  9. Central estrogenic pathways protect against the depressant action of acute nicotine on reflex tachycardia in female rats

    SciTech Connect

    El-Mas, Mahmoud M. Fouda, Mohamed A.; El-gowilly, Sahar M.; Saad, Evan I.

    2012-02-01

    We have previously shown that acute exposure of male rats to nicotine preferentially attenuates baroreceptor-mediated control of reflex tachycardia in contrast to no effect on reflex bradycardia. Here, we investigated whether female rats are as sensitive as their male counterparts to the baroreflex depressant effect of nicotine and whether this interaction is modulated by estrogen. Baroreflex curves relating reflex chronotropic responses evoked by i.v. doses (1–16 μg/kg) of phenylephrine (PE) or sodium nitroprusside (SNP), were constructed in conscious freely moving proestrus, ovariectomized (OVX), and estrogen (50 μg/kg/day s.c., 5 days)-replaced OVX (OVXE{sub 2}) rats. Slopes of the curves were taken as a measure of baroreflex sensitivity (BRS{sub PE} and BRS{sub SNP}). Nicotine (100 μg/kg i.v.) reduced BRS{sub SNP} in OVX rats but not in proestrus or OVXE{sub 2} rats. The attenuation of reflex tachycardia by nicotine was also evident in diestrus rats, which exhibited plasma estrogen levels similar to those of OVX rats. BRS{sub PE} was not affected by nicotine in all rat preparations. Experiments were then extended to determine whether central estrogenic receptors modulate the nicotine–BRS{sub SNP} interaction. Intracisteral (i.c.) treatment of OVX rats with estrogen sulfate (0.2 μg/rat) abolished the BRS{sub SNP} attenuating effect of i.v. nicotine. This protective effect of estrogen disappeared when OVX rats were pretreated with i.c. ICI 182,780 (50 μg/rat, selective estrogen receptor antagonist). Together, these findings suggest that central neural pools of estrogen receptors underlie the protection offered by E{sub 2} against nicotine-induced baroreceptor dysfunction in female rats. -- Highlights: ► Estrogen protects against the depressant effect of nicotine on reflex tachycardia. ► The baroreflex response and estrogen status affect the nicotine–BRS interaction. ► The protection offered by estrogen is mediated via central estrogen receptors.

  10. Giant retinal tears.

    PubMed

    Shunmugam, Manoharan; Ang, Ghee Soon; Lois, Noemi

    2014-01-01

    A giant retinal tear (GRT) is a full-thickness neurosensory retinal break that extends circumferentially around the retina for three or more clock hours in the presence of a posteriorly detached vitreous. Its incidence in large population-based studies has been estimated as 1.5% of rhegmatogenous retinal detachments, with a significant male preponderance, and bilaterality in 12.8%. Most GRTs are idiopathic, with trauma, hereditary vitreoretinopathies and high myopia each being causative in decreasing frequency. The vast majority of GRTs are currently managed with a pars plana vitrectomy; the use of adjunctive circumferential scleral buckling is debated, but no studies have shown a clear anatomical or visual advantage with its use. Similarly, silicone oil tamponade does not influence long-term outcomes when compared with gas. Primary and final retinal reattachment rates are achieved in 88% and 95% of patients, respectively. Even when the retina remains attached, however, visual recovery may be limited. Furthermore, fellow eyes of patients with a GRT are at higher risk of developing retinal tears and retinal detachment. Prophylactic treatment under these circumstances may be considered but there is no firm evidence of its efficacy at the present time. PMID:24138895

  11. Finite element modeling of retinal prosthesis mechanics

    NASA Astrophysics Data System (ADS)

    Basinger, B. C.; Rowley, A. P.; Chen, K.; Humayun, M. S.; Weiland, J. D.

    2009-10-01

    Epiretinal prostheses used to treat degenerative retina diseases apply stimulus via an electrode array fixed to the ganglion cell side of the retina. Mechanical pressure applied by these arrays to the retina, both during initial insertion and throughout chronic use, could cause sufficient retinal damage to reduce the device's effectiveness. In order to understand and minimize potential mechanical damage, we have used finite element analysis to model mechanical interactions between an electrode array and the retina in both acute and chronic loading configurations. Modeling indicates that an acute tacking force distributes stress primarily underneath the tack site and heel edge of the array, while more moderate chronic stresses are distributed more evenly underneath the array. Retinal damage in a canine model chronically implanted with a similar array occurred in correlating locations, and model predictions correlate well with benchtop eyewall compression tests. This model provides retinal prosthesis researchers with a tool to optimize the mechanical electrode array design, but the techniques used here represent a unique effort to combine a modifiable device and soft biological tissues in the same model and those techniques could be extended to other devices that come into mechanical contact with soft neural tissues.

  12. Changes in retinal vessels related to varicocele: a pilot investigation.

    PubMed

    Coşkun, M; Ilhan, N; Elbeyli, A; Rifaioğlu, M M; Inci, M; Davran, R; Tuzcu, E A; Yarbağ, A; Davarci, M; Gökçe, A

    2016-06-01

    The aim of this study was to investigate whether retinal vasculature changes had occurred (retinal artery diameter, retinal vein diameter and artery/vein ratio) in patients with varicocele. This pilot study included 50 healthy subjects with any eye disease apart from slight refractive errors and 55 patients with varicocele. Retinal arteriolar and venular diameters were measured and summarised as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Retinal microvascular diameters and the arteriolar-to-venular ratio (AVR) were assessed with a digital retinal camera. All measurements and calculations were performed using a computer-based program. The mean CRAE value was 151.8 ± 3.6 μm in the study group and 150.4 ± 4.5 μm in the control group. Mean CRVE value was 209.4 ± 5.9 μm in the study group and 200.1 ± 8.7 μm in the control group. AVR was found 0.72 ± 0.02 in the study group and 0.75 ± 0.03 in the control group. There were significant differences between groups in terms of CRVE and AVR. There were no significant differences between groups in terms of CRAE. The results of this study showed that the patients with varicocele showed significant changes on retinal vascular diameter. PMID:26314401

  13. Hospital Performance Indicators and Their Associated Factors in Acute Child Poisoning at a Single Poison Center, Central Saudi Arabia.

    PubMed

    Alanazi, Menyfah Q; Al-Jeriasy, Majed I; Al-Assiri, Mohammed H; Afesh, Lara Y; Alhammad, Fahad; Salam, Mahmoud

    2015-12-01

    Admission rate and length of stay (LOS) are two hospital performance indicators that affect the quality of care, patients' satisfaction, bed turnover, and health cost expenditures. The aim of the study was to identify factors associated with higher admission rates and extended average LOS among acutely poisoned children at a single poison center, central Saudi Arabia.This is a cross-sectional, poison and medical chart review between 2009 and 2011. Exposures were child characteristics, that is, gender, age, body mass index (BMI), health history, and Canadian 5-level triage scale. Poison incident characteristics were, that is, type, exposure route, amount, form, home remedy, and arrival time to center. Admission status and LOS were obtained from records. Chronic poisoning, plant allergies, and venomous bites were excluded. Bivariate and regression analyses were applied. Significance at P < 0.05.Of the 315 eligible cases, (72%) were toddlers with equal gender distribution, (58%) had normal BMI, and (77%) were previously healthy. Poison substances were pharmaceutical drugs (63%) versus chemical products (37%). Main exposure route was oral (98%). Home remedy was observed in (21.9%), which were fluids, solutes, and/or gag-induced vomiting. Almost (52%) arrived to center >1 h. Triage levels: non-urgent cases (58%), less urgent (11%), urgent (18%), emergency (12%), resuscitative (1%). Admission rate was (20.6%) whereas av. LOS was 13 ± 22 h. After adjusting and controlling for confounders, older children (adj.OR = 1.19) and more critical triage levels (adj.OR = 1.35) were significantly associated with higher admission rates compared to younger children and less critical triage levels (adj.P = 0.006) and (adj.P = 0.042) respectively. Home remedy prior arrival was significantly associated with higher av. LOS (Beta = 9.48, t = 2.99), compared to those who directly visited the center, adj.P = 0.003.Hospital administrators are cautioned

  14. Progressive outer retinal necrosis-like retinitis in immunocompetent hosts.

    PubMed

    Chawla, Rohan; Tripathy, Koushik; Gogia, Varun; Venkatesh, Pradeep

    2016-01-01

    We describe two young immunocompetent women presenting with bilateral retinitis with outer retinal necrosis involving posterior pole with centrifugal spread and multifocal lesions simulating progressive outer retinal necrosis (PORN) like retinitis. Serology was negative for HIV and CD4 counts were normal; however, both women were on oral steroids at presentation for suspected autoimmune chorioretinitis. The retinitis in both eyes responded well to oral valaciclovir therapy. However, the eye with the more fulminant involvement developed retinal detachment with a loss of vision. Retinal atrophy was seen in the less involved eye with preservation of vision. Through these cases, we aim to describe a unique evolution of PORN-like retinitis in immunocompetent women, which was probably aggravated by a short-term immunosuppression secondary to oral steroids. PMID:27511757

  15. Photovoltaic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Loudin, James; Mathieson, Keith; Kamins, Ted; Wang, Lele; Galambos, Ludwig; Huie, Philip; Sher, Alexander; Harris, James; Palanker, Daniel

    2011-03-01

    Electronic retinal prostheses seek to restore sight to patients suffering from retinal degenerative disorders. Implanted electrode arrays apply patterned electrical stimulation to surviving retinal neurons, producing visual sensations. All current designs employ inductively coupled coils to transmit power and/or data to the implant. We present here the design and initial testing of a photovoltaic retinal prosthesis fabricated with a pixel density of up to 177 pixels/mm2. Photodiodes within each pixel of the subretinal array directly convert light to stimulation current, avoiding the use of bulky coil implants, decoding electronics, and wiring, and thereby reducing surgical complexity. A goggles-mounted camera captures the visual scene and transmits the data stream to a pocket processor. The resulting images are projected into the eyes by video goggles using pulsed, near infrared (~900 nm) light. Prostheses with three pixel densities (15, 55, and 177 pix/mm2) are being fabricated, and tests indicate a charge injection limit of 1.62 mC/cm2 at 25Hz. In vitro tests of the photovoltaic retinal stimulation using a 512-element microelectrode array have recorded stimulated spikes from the ganglion cells, with latencies in the 1-100ms range, and with peak irradiance stimulation thresholds varying from 0.1 to 1 mW/mm2. With 1ms pulses at 25Hz the average irradiance is more than 100 times below the IR retinal safety limit. Elicited retinal response disappeared upon the addition of synaptic blockers, indicating that the inner retina is stimulated rather than the ganglion cells directly, and raising hopes that the prosthesis will preserve some of the retina's natural signal processing.

  16. In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy

    PubMed Central

    Uddin, Md. Imam; Evans, Stephanie M.; Craft, Jason R.; Capozzi, Megan E.; McCollum, Gary W.; Yang, Rong; Marnett, Lawrence J.; Uddin, Md. Jashim; Jayagopal, Ashwath; Penn, John S.

    2016-01-01

    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. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs. PMID:27491345

  17. In Vivo Imaging of Retinal Hypoxia in a Model of Oxygen-Induced Retinopathy.

    PubMed

    Uddin, Md Imam; Evans, Stephanie M; Craft, Jason R; Capozzi, Megan E; McCollum, Gary W; Yang, Rong; Marnett, Lawrence J; Uddin, Md Jashim; Jayagopal, Ashwath; Penn, John S

    2016-01-01

    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. HYPOX-4 dependent in vivo and ex vivo imaging of hypoxia was tested in a mouse model of oxygen-induced retinopathy (OIR). Predicted patterns of retinal hypoxia were imaged by HYPOX-4 dependent fluorescence activity in this animal model. In retinal cells and mouse retinal tissue, pimonidazole-adduct immunostaining confirmed the hypoxia selectivity of HYPOX-4. HYPOX-4 had no effect on retinal cell proliferation as indicated by BrdU assay and exhibited no acute toxicity in retinal tissue as indicated by TUNEL assay and electroretinography (ERG) analysis. Therefore, HYPOX-4 could potentially serve as the basis for in vivo fluorescence-based hypoxia-imaging techniques, providing a tool for investigators to understand the pathogenesis of ischemic retinopathies and for physicians to address unmet clinical needs. PMID:27491345

  18. Outcomes and Acute Toxicities of Proton Therapy for Pediatric Atypical Teratoid/Rhabdoid Tumor of the Central Nervous System

    SciTech Connect

    McGovern, Susan L.; Okcu, M. Fatih; Munsell, Mark F.; Kumbalasseriyil, Nancy; Grosshans, David R.; McAleer, Mary F.; Chintagumpala, Murali; Khatua, Soumen; Mahajan, Anita

    2014-12-01

    Purpose: Atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system is a rare cancer primarily affecting children younger than 5 years old. Because patients are young and receive intensive chemotherapy, there is concern regarding late radiation toxicity, particularly as survival rates improve. Therefore, there is interest in using proton therapy to treat these tumors. This study was undertaken to investigate outcomes and acute toxicities associated with proton therapy for AT/RT. Methods and Materials: The records of 31 patients with AT/RT treated with proton radiation from October 2008 to August 2013 were reviewed. Demographics, treatment characteristics, and outcomes were recorded and analyzed. Results: Median age at diagnosis was 19 months (range, 4-55 months), with a median age at radiation start of 24 months (range, 6-62 months). Seventeen patients received local radiation with a median dose of 50.4 GyRBE (range, 9-54 GyRBE). Fourteen patients received craniospinal radiation; half received 24 GyRBE or less, and half received 30.6 GyRBE or more. For patients receiving craniospinal radiation, the median tumor dose was 54 GyRBE (range, 43.2-55.8 GyRBE). Twenty-seven patients (87%) completed the planned radiation. With median follow-up of 24 months for all patients (range, 3-53 months), median progression-free survival was 20.8 months and median overall survival was 34.3 months. Five patients (16%) developed clinical findings and imaging changes in the brainstem 1 to 4 months after radiation, consistent with radiation reaction; all cases resolved with steroids or bevacizumab. Conclusions: This is the largest report of children with AT/RT treated with proton therapy. Preliminary survival outcomes in this young pediatric population are encouraging compared to historic results, but further study is warranted.

  19. The acute effect of maximal exercise on central and peripheral arterial stiffness indices and hemodynamics in children and adults.

    PubMed

    Melo, Xavier; Fernhall, Bo; Santos, Diana A; Pinto, Rita; Pimenta, Nuno M; Sardinha, Luís B; Santa-Clara, Helena

    2016-03-01

    This study compared the effects of a bout of maximal running exercise on arterial stiffness in children and adults. Right carotid blood pressure and artery stiffness indices measured by pulse wave velocity (PWV), compliance and distensibility coefficients, stiffness index α and β (echo-tracking), contralateral carotid blood pressure, and upper and lower limb and central/aortic PWV (applanation tonometry) were taken at rest and 10 min after a bout of maximal treadmill running in 34 children (7.38 ± 0.38 years) and 45 young adults (25.22 ± 0.91 years) having similar aerobic potential. Two-by-two repeated measures analysis of variance and analysis of covariance were used to detect differences with exercise between groups. Carotid pulse pressure (PP; η(2) = 0.394) increased more in adults after exercise (p < 0.05). Compliance (η(2) = 0.385) decreased in particular in adults and in those with high changes in distending pressure, similarly to stiffness index α and β. Carotid PWV increased more in adults and was related to local changes in PP but not mean arterial pressure (MAP). Stiffness in the lower limbs decreased (η(2) = 0.115) but apparently only in those with small MAP changes (η(2) = 0.111). No significant exercise or group interaction effects were found when variables were adjusted to height. An acute bout of maximal exercise can alter arterial stiffness and hemodynamics in the carotid artery and within the active muscle beds. Arterial stiffness and hemodynamic response to metabolic demands during exercise in children simply reflect their smaller body size and may not indicate a particular physiological difference compared with adults. PMID:26842667

  20. Peripheral retinal non-perfusion and treatment response in branch retinal vein occlusion

    PubMed Central

    Abri Aghdam, Kaveh; Reznicek, Lukas; Soltan Sanjari, Mostafa; Framme, Carsten; Bajor, Anna; Klingenstein, Annemarie; Kernt, Marcus; Seidensticker, Florian

    2016-01-01

    AIM To evaluate the association between the size of peripheral retinal non-perfusion and the number of intravitreal ranibizumab injections in patients with treatment-naive branch retinal vein occlusion (BRVO) and macular edema. METHODS A total of 53 patients with treatment-naive BRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography (OCT) imaging and ultra wide-field fluorescein angiography (UWFA). Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmological Society. Two independent, masked graders quantified the areas of peripheral retinal non-perfusion. RESULTS Intravitreal injections improved best-corrected visual acuity (BCVA) significantly from 22.23±16.33 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters to 36.23±15.19 letters (P<0.001), and mean central subfield thickness significantly reduced from 387±115 µm to 321±115 µm (P=0.01). Mean number of intravitreal ranibizumab injections was 3.61±1.56. The size of retinal non-perfusion correlated significantly with the number of intravitreal ranibizumab injections (R=0.724, P<0.001). CONCLUSION Peripheral retinal non-perfusion in patients with BRVO associates significantly with intravitreal ranibizumab injections in patients with BRVO and macular edema. PMID:27366688

  1. Vitamin A Derivatives as Treatment Options for Retinal Degenerative Diseases

    PubMed Central

    Perusek, Lindsay; Maeda, Tadao

    2013-01-01

    The visual cycle is a sequential enzymatic reaction for vitamin A, all-trans-retinol, occurring in the outer layer of the human retina and is essential for the maintenance of vision. The central source of retinol is derived from dietary intake of both retinol and pro-vitamin A carotenoids. A series of enzymatic reactions, located in both the photoreceptor outer segment and the retinal pigment epithelium, transform retinol into the visual chromophore 11-cis-retinal, regenerating visual pigments. Retina specific proteins carry out the majority of the visual cycle, and any significant interruption in this sequence of reactions is capable of causing varying degrees of blindness. Among these important proteins are Lecithin:retinol acyltransferase (LRAT) and retinal pigment epithelium-specific 65-kDa protein (RPE65) known to be responsible for esterification of retinol to all-trans-retinyl esters and isomerization of these esters to 11-cis-retinal, respectively. Deleterious mutations in these genes are identified in human retinal diseases that cause blindness, such as Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Herein, we discuss the pathology of 11-cis-retinal deficiency caused by these mutations in both animal disease models and human patients. We also review novel therapeutic strategies employing artificial visual chromophore 9-cis-retinoids which have been employed in clinical trials involving LCA patients. PMID:23857173

  2. Probabilistic retinal vessel segmentation

    NASA Astrophysics Data System (ADS)

    Wu, Chang-Hua; Agam, Gady

    2007-03-01

    Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

  3. Congenital retinal macrovessel: atypical presentation using optical coherence tomography.

    PubMed

    Ceylan, Osman M; Gullulu, Gulay; Akin, Tugrul; Bilen, Harun

    2011-02-01

    To describe a congenital retinal macrovessel with macular thickening. This case was investigated using fundus photography, fluorescein angiography, Spectralis optical coherence tomography and a 10-2 visual field test. A 23-year-old man was referred to our clinic with decreased vision in the right eye. Fundus examination of the right eye revealed a congenital retinal macrovessel that originated inferior to the superotemporal branch of the central retinal vein. Using fluorescein angiography, early filling and delayed emptying of the aberrant vein were observed. Spectralis optical coherence tomography demonstrated macular thickening and was supported by a 10-2 visual field test that revealed a relative scotoma corresponding to the same location. At the 18-month follow-up, visual acuity remained stable. Although rare, this case demonstrated that macular thickening can cause decreased visual acuity in the presence of a congenital retinal macrovessel. PMID:20922460

  4. Preparation of embryonic retinal explants to study CNS neurite growth.

    PubMed

    Hanea, Sonia T; Shanmugalingam, Ushananthini; Fournier, Alyson E; Smith, Patrice D

    2016-05-01

    This protocol outlines the preparation of embryonic mouse retinal explants, which provides an effective technique to analyze neurite outgrowth in central nervous system (CNS) neurons. This validated ex vivo system, which displays limited neuronal death, is highly reproducible and particularly amenable to manipulation. Our previously published studies involving embryonic chick or adult mouse retinal explants were instrumental in the preparation of this protocol; aspects of these previous techniques were combined, adopted and optimized. This protocol thus permits more efficient analysis of neurite growth. Briefly, the retina is dissected from the embryonic mouse eye using precise techniques that take into account the small size of the embryonic eye. The approach applied ensures that the retinal ganglion cell (RGC) layer faces the adhesion substrate on coated cover slips. Neurite growth is clear, well-delineated and readily quantifiable. These retinal explants can therefore be used to examine the neurite growth effects elicited by potential therapeutic agents. PMID:27072342

  5. Retinal lesions in septicemia.

    PubMed

    Neudorfer, M; Barnea, Y; Geyer, O; Siegman-Igra, Y

    1993-12-15

    We explored the association between septicemia and specific retinal lesions in a prospective controlled study. Hemorrhages, cotton-wool spots, or Roth's spots were found in 24 of 101 septicemic patients (24%), compared to four of 99 age- and gender-matched control patients (4%) (P = .0002). There was no significant association between types of organisms or focus of infection and the presence of specific lesions. Histologic examination of affected eyes disclosed cytoid bodies in the nerve fiber layer without inflammation. A definite association between septicemia and retinal lesions was found and indicates the need for routine ophthalmoscopy in septicemic patients. PMID:8250076

  6. Pathway to Retinal Oximetry

    PubMed Central

    Beach, James

    2014-01-01

    Events and discoveries in oxygen monitoring over the past two centuries are presented as the background from which oximetry of the human retina evolved. Achievements and the people behind them are discussed, showing parallels between the work in tissue measurements and later in the eye. Developments in the two-wavelength technique for oxygen saturation measurements in retinal vessels are shown to exploit the forms of imaging technology available over time. The last section provides a short summary of the recent research in retinal diseases using vessel oximetry. PMID:25237591

  7. Retinal compensatory changes after light damage in albino mice

    PubMed Central

    Montalbán-Soler, Luis; Alarcón-Martínez, Luis; Jiménez-López, Manuel; Salinas-Navarro, Manuel; Galindo-Romero, Caridad; Bezerra de Sá, Fabrízio; García-Ayuso, Diego; Avilés-Trigueros, Marcelino; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta

    2012-01-01

    Purpose To investigate the anatomic and functional changes triggered by light exposure in the albino mouse retina and compare them with those observed in the albino rat. Methods BALB/c albino mice were exposed to 3,000 lx of white light during 24 h and their retinas analyzed from 1 to 180 days after light exposure (ALE). Left pupil mydriasis was induced with topical atropine. Retinal function was analyzed by electroretinographic (ERG) recording. To assess retinal degeneration, hematoxylin and eosin staining, the TdT-mediated dUTP nick-end labeling (TUNEL) technique, and quantitative immunohistofluorescence for synaptophysin and protein kinase Cα (PKCα) were used in cross sections. Intravenous injection of horseradish peroxidase and Fluoro-Gold™ tracing were used in whole-mounted retinas to study the retinal vasculature and the retinal ganglion cell (RGC) population, respectively. Results Light exposure caused apoptotic photoreceptor death in the central retina. This death was more severe in the dorsal than in the ventral retina, sparing the periphery. Neither retinal vascular leakage nor retinal ganglion cell death was observed ALE. The electroretinographic a-wave was permanently impaired, while the b-wave decreased but recovered gradually by 180 days ALE. The scotopic threshold responses, associated with the inner retinal function, diminished at first but recovered completely by 14 days ALE. This functional recovery was concomitant with the upregulation of protein kinase Cα and synaptophysin. Similar results were obtained in both eyes, irrespective of mydriasis. Conclusions In albino mice, light exposure induces substantial retinal damage, but the surviving photoreceptors, together with compensatory morphological/molecular changes, allow an important restoration of the retinal function. PMID:22509098

  8. Macular pigment optical density is related to serum lutein in retinitis pigmentosa

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: To determine whether macular pigment optical density (MPOD) is related to the degree of cystoid macular edema (CME) in patients with retinitis pigmentosa. Methods: We measured MPOD with heterochromatic flicker photometry and central foveal retinal thickness with optical coherence tomography...

  9. Comparison of central nervous system prophylaxis with cranial radiation and intrathecal methotrexate versus intrathecal methotrexate alone in acute lymphoblastic leukemia

    SciTech Connect

    Muriel, F.S.; Svarch, E.; Pavlovsky, S.; Eppinger-Helft, M.; Braier, J.; Vergara, B.; Garay, G.; Kvicala, R.; Divito, J.M.; Failace, R.

    1983-08-01

    In acute lymphoblastic leukemia, central nervous system prophylaxis with irradiation plus intrathecal methotrexate (i.t. MTX) reduces the incidence of CNS relapse to 7%-15%. However, increased evidence of CNS delayed toxicity was recognized mainly in children as CT scan abnormalities and neuropsychologic alterations. Two questions were analyzed: (1) Will further doses of i.t. methotraxate and dexamethasone (i.t. MTX-DMT) decrease the incidence of CNS relapse. (2) Is i.t. MTX-DMT given during induction and maintenance as effective as cranium irradiation plus i.t. MTX-DMT. Incidence of primary CNS relapse in i.t. MTX-DMT-treated patients with a WBC count < 50,000 and in the untreated group was 11%. In patients with a WBC count > 50,000, it was 16% in the treated group and 19% in the control group. These patients were compared with patients which had received 3 doses of i.t. MTX-DMT alone during induction, 3 doses weekly during the first month of remission, and quarterly thereafter. The incidence of leukemia at 60 mo in patients with a WBC count < 50,000 was 20% in the irradiated group and 32% in the group with i.t. MTX-DMT alone. The relapse-free survival at 60 mo was 26% and 41%, respectively, (p < 0.0005). The incidence in patients with a WBC count > 50,000 at 48 mo was 28% and 42% in the irradiated and nonirradiated group respectively. Complete remission remained at 15% and 16% respectively of patients disease-free at 48 mo. We conclude that (A) after cranial irradiation plus i.t. MTX-DMT X 5, the use of additional doses of i.t. MTX-DMT is not of further benefit in preventing CNS relapse; (B) use of i.t. MTX-DMT alone compares with cranial irradiation plus i.t. MTX-DMT in incidence of CNS relapse; and (C) relapse-free survival and survival in patients with a WBC count < 50.000 were significantly longer in those without cranial irradiation.

  10. Unilateral Ischemic Maculopathy Associated with Cytomegalovirus Retinitis in Patients with AIDS: Optical Coherence Tomography Findings.

    PubMed

    Arevalo, J Fernando; Garcia, Reinaldo A; Arevalo, Fernando A; Fernandez, Carlos F

    2015-01-01

    To describe the clinical and optical coherence tomography (OCT) characteristics of ischemic maculopathy in two patients with acquired immunodeficiency syndrome (AIDS). Two patients with AIDS and cytomegalovirus (CMV) retinitis developed ischemic maculopathy. Both patients presented with central visual loss and active granular CMV retinitis. The presence of opacification of the superficial retina in the macular area and intraretinal edema suggested the diagnosis. Fluorescein angiography changes were similar in the two cases with enlargement of the foveal avascular zone and late staining of juxtafoveal vessels. OCT changes were suggestive of retinal ischemia: Increased reflectivity from the inner retinal layer and decreased backscattering from the retinal photoreceptors due to fluid and retinal edema. Ischemic maculopathy may cause a severe and permanent decrease in vision in AIDS patients. Fluorescein angiography and OCT should be considered in any patient with AIDS and unexplained visual loss. The mechanism of ischemic maculopathy may be multifactorial. PMID:27051496

  11. Unilateral Ischemic Maculopathy Associated with Cytomegalovirus Retinitis in Patients with AIDS: Optical Coherence Tomography Findings

    PubMed Central

    Arevalo, J. Fernando; Garcia, Reinaldo A.; Arevalo, Fernando A.; Fernandez, Carlos F.

    2015-01-01

    To describe the clinical and optical coherence tomography (OCT) characteristics of ischemic maculopathy in two patients with acquired immunodeficiency syndrome (AIDS). Two patients with AIDS and cytomegalovirus (CMV) retinitis developed ischemic maculopathy. Both patients presented with central visual loss and active granular CMV retinitis. The presence of opacification of the superficial retina in the macular area and intraretinal edema suggested the diagnosis. Fluorescein angiography changes were similar in the two cases with enlargement of the foveal avascular zone and late staining of juxtafoveal vessels. OCT changes were suggestive of retinal ischemia: Increased reflectivity from the inner retinal layer and decreased backscattering from the retinal photoreceptors due to fluid and retinal edema. Ischemic maculopathy may cause a severe and permanent decrease in vision in AIDS patients. Fluorescein angiography and OCT should be considered in any patient with AIDS and unexplained visual loss. The mechanism of ischemic maculopathy may be multifactorial. PMID:27051496

  12. Neuroprotective therapy for argon-laser-induced retinal injury

    NASA Astrophysics Data System (ADS)

    Belkin, Michael; Rosner, Mordechai; Solberg, Yoram; Turetz, Yosef

    1999-06-01

    Laser photocoagulation treatment of the central retina is often complicated by an immediate side effect of visual impairment, caused by the unavoidable laser-induced destruction of the normal tissue lying adjacent to the lesion and not affected directly by the laser beam. Furthermore, accidental laser injuries are at present untreatable. A neuroprotective therapy for salvaging the normal tissue might enhance the benefit obtained from treatment and allow safe perifoveal photocoagulation. We have developed a rat model for studying the efficacy of putative neuroprotective compounds in ameliorating laser-induced retinal damage. Four compounds were evaluated: the corticosteroid methylprednisolone, the glutamate-receptor blocker MK-801, the anti-oxidant enzyme superoxide dismutase, and the calcim-overload antagonist flunarizine. The study was carried out in two steps: in the first, the histopathological development of retinal laser injuries was studied. Argon laser lesions were inflicted in the retinas of 18 pigmented rats. The animals were sacrificed after 3, 20 or 60 days and their retinal lesions were evaluated under the light microscope. The laser injury mainly involved the outer layers of the retina, where it destroyed significant numbers of photoreceptor cells. Over time, evidence of two major histopathological processes was observed: traction of adjacent nomral retinal cells into the central area of the lesion forming an internal retinal bulging, and a retinal pigmented epithelial proliferative reaction associated with subretinal neovascularization and invations of the retinal lesion site by phagocytes. The neuroprotective effects of each of the four compounds were verified in a second step of the study. For each drug tested, 12 rats were irradiated wtih argon laser inflictions: six of them received the tested agent while the other six were treated with the corresponding vehicle. Twenty days after laser expsoure, the rats were sacrificed and their lesions were

  13. Meningocele-induced positional syncope and retinal hemorrhage.

    PubMed

    Bekavac, Ivo; Halloran, John I

    2003-05-01

    Meningocele is recognized as a rare, usually asymptomatic condition not associated with acute neurologic symptoms. We herein describe the case of a patient with a longstanding history of a lower back "mass" and recurrent syncope who became acutely unresponsive and developed bilateral retinal hemorrhages when she was placed in the supine position to undergo carotid sonography. MR imaging revealed a large, dorsal lumbar meningocele. The episode likely was caused by acutely increased intracranial pressure caused by displacement of CSF from the meningocele intracranially. PMID:12748081

  14. Histone Deacetylase Inhibition Restores Retinal Pigment Epithelium Function in Hyperglycemia.

    PubMed

    Desjardins, Danielle; Liu, Yueying; Crosson, Craig E; Ablonczy, Zsolt

    2016-01-01

    In diabetic individuals, macular edema is a major cause of vision loss. This condition is refractory to insulin therapy and has been attributed to metabolic memory. The retinal pigment epithelium (RPE) is central to maintaining fluid balance in the retina, and this function is compromised by the activation of advanced glycation end-product receptors (RAGE). Here we provide evidence that acute administration of the RAGE agonist, glycated-albumin (gAlb) or vascular endothelial growth factor (VEGF), increased histone deacetylase (HDAC) activity in RPE cells. The administration of the class I/II HDAC inhibitor, trichostatin-A (TSA), suppressed gAlb-induced reductions in RPE transepithelial resistance (in vitro) and fluid transport (in vivo). Systemic TSA also restored normal RPE fluid transport in rats with subchronic hyperglycemia. Both gAlb and VEGF increased HDAC activity and reduced acetyl-α-tubulin levels. Tubastatin-A, a relatively specific antagonist of HDAC6, inhibited gAlb-induced changes in RPE cell resistance. These data are consistent with the idea that RPE dysfunction following exposure to gAlb, VEGF, or hyperglycemia is associated with increased HDAC6 activity and decreased acetyl-α-tubulin. Therefore, we propose inhibiting HDAC6 in the RPE as a potential therapy for preserving normal fluid homeostasis in the hyperglycemic retina. PMID:27617745

  15. Bilateral Rhegmatogenous Retinal Detachment during External Beam Radiotherapy.

    PubMed

    Hidaka, Takako; Chuman, Hideki; Nao-I, Nobuhisa

    2016-01-01

    Herein, we report a case of nontraumatic bilateral rhegmatogenous retinal detachment (RRD) during external beam radiotherapy for nonocular tumor, presented as an observational case study in conjunction with a review of the relevant literature. A 65-year-old male was referred to our hospital due to bilateral RRD. He underwent a biopsy for a tumor of the left frontal lobe 4 months prior to presentation, and the tumor had been diagnosed as primary central nerve system B-cell type lymphoma. He received chemotherapy and external beam radiotherapy for 1 month. There were no traumatic episodes. Bilateral retinal detachment occurred during a series of radiotherapies. Simultaneous nontraumatic bilateral retinal detachment is rare. The effects of radiotherapy on ocular functionality, particularly in cases involving retinal adhesion and vitreous contraction, may include RRD. Thus, it is necessary to closely monitor the eyes of patients undergoing radiotherapy, particularly those undergoing surgery for retinal detachment and those with a history of photocoagulation for retinal tears, a relevant family history, or risk factors known to be associated with RRD. PMID:27462261

  16. Bilateral Rhegmatogenous Retinal Detachment during External Beam Radiotherapy

    PubMed Central

    Hidaka, Takako; Chuman, Hideki; Nao-i, Nobuhisa

    2016-01-01

    Herein, we report a case of nontraumatic bilateral rhegmatogenous retinal detachment (RRD) during external beam radiotherapy for nonocular tumor, presented as an observational case study in conjunction with a review of the relevant literature. A 65-year-old male was referred to our hospital due to bilateral RRD. He underwent a biopsy for a tumor of the left frontal lobe 4 months prior to presentation, and the tumor had been diagnosed as primary central nerve system B-cell type lymphoma. He received chemotherapy and external beam radiotherapy for 1 month. There were no traumatic episodes. Bilateral retinal detachment occurred during a series of radiotherapies. Simultaneous nontraumatic bilateral retinal detachment is rare. The effects of radiotherapy on ocular functionality, particularly in cases involving retinal adhesion and vitreous contraction, may include RRD. Thus, it is necessary to closely monitor the eyes of patients undergoing radiotherapy, particularly those undergoing surgery for retinal detachment and those with a history of photocoagulation for retinal tears, a relevant family history, or risk factors known to be associated with RRD. PMID:27462261

  17. Fibrinogen and rhegmatogenous retinal detachment: a pilot prospective study

    PubMed Central

    Theocharis, IP

    2010-01-01

    Purpose: To examine the correlation, if any, between fibrinogen plasma levels (FPL) and the clinical features of rhegmatogenous retinal detachment (RRD). Methods: FPL were measured preoperatively in 33 patients with primary RRD. Patient characteristics and detachment features such as the numbers of breaks and the extent of the detachment were recorded; Results: No statistically significant correlation was found between FPL and the number of breaks. A statistically significant correlation was found between FPL and the extent of the RRD, even if the influence of the number of breaks was excluded. Conclusions: FPL correlate with retinal detachment extent, which implicates an acute inflammatory response to detachment traumatic phenomenon or a role of the fibrinogen molecule in retinal adhesiveness. PMID:20186280

  18. Retinal Detachment: Torn or Detached Retina Diagnosis

    MedlinePlus

    ... Eye Health / Eye Health A-Z Detached or Torn Retina Sections Retinal Detachment: What Is a Torn ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment: Torn or Detached Retina Diagnosis Written by: Kierstan Boyd ...

  19. Retinal Detachment: Torn or Detached Retina Symptoms

    MedlinePlus

    ... Eye Health / Eye Health A-Z Detached or Torn Retina Sections Retinal Detachment: What Is a Torn ... Retina Treatment Retinal Detachment Vision Simulator Retinal Detachment: Torn or Detached Retina Symptoms Written by: Kierstan Boyd ...

  20. Uveitic angle closure glaucoma in a patient with inactive cytomegalovirus retinitis and immune recovery uveitis.

    PubMed

    Goldberg, Daniel E; Freeman, William R

    2002-01-01

    We report a case of uveitic acute angle closure glaucoma in a patient with acquired immunodeficiency syndrome (AIDS) associated with inactive cytomegalovirus retinitis and immune recovery vitritis. We conducted a long-term, follow-up examination of a 47-year-old male with AIDS and inactive cytomegalovirus retinitis caused by immune recovery on highly active antiretroviral therapy (HAART). We found vitritis and ultimate development of uveitic glaucoma in the postoperative periods following repair of retinal detachment and extracapsular cataract extraction with intraocular lens implant. An episode of acute angle closure secondary to posterior synechiae and iris bombé subsequently developed, requiring peripheral laser iridotomy. Immune recovery in the setting of inactive cytomegalovirus retinitis can result in intraocular inflammation severe enough to cause angle closure glaucoma and profound ocular morbidity. PMID:12358297

  1. Small Animal Retinal Imaging

    NASA Astrophysics Data System (ADS)

    Choi, WooJhon; Drexler, Wolfgang; Fujimoto, James G.

    Developing and validating new techniques and methods for small animal imaging is an important research area because there are many small animal models of retinal diseases such as diabetic retinopathy, age-related macular degeneration, and glaucoma [1-6]. Because the retina is a multilayered structure with distinct abnormalities occurring in different intraretinal layers at different stages of disease progression, there is a need for imaging techniques that enable visualization of these layers individually at different time points. Although postmortem histology and ultrastructural analysis can be performed for investigating microscopic changes in the retina in small animal models, this requires sacrificing animals, which makes repeated assessment of the same animal at different time points impossible and increases the number of animals required. Furthermore, some retinal processes such as neurovascular coupling cannot be fully characterized postmortem.

  2. Inherited Retinal Degenerative Disease Registry

    ClinicalTrials.gov

    2016-03-21

    Eye Diseases Hereditary; Retinal Disease; Achromatopsia; Bardet-Biedl Syndrome; Bassen-Kornzweig Syndrome; Batten Disease; Best Disease; Choroidal Dystrophy; Choroideremia; Cone Dystrophy; Cone-Rod Dystrophy; Congenital Stationary Night Blindness; Enhanced S-Cone Syndrome; Fundus Albipunctatus; Goldmann-Favre Syndrome; Gyrate Atrophy; Juvenile Macular Degeneration; Kearns-Sayre Syndrome; Leber Congenital Amaurosis; Refsum Syndrome; Retinitis Pigmentosa; Retinitis Punctata Albescens; Retinoschisis; Rod-Cone Dystrophy; Rod Dystrophy; Rod Monochromacy; Stargardt Disease; Usher Syndrome

  3. [News in Retinal Imaging].

    PubMed

    Werkmeister, R; Schmidl, D; Garhöfer, G; Schmetterer, L

    2015-09-01

    New developments in retinal imaging have revolutionised ophthalmology in recent years. In particular, optical coherence tomography (OCT) provides highly resolved and well reproducible images and has rung in a new era in ophthalmological imaging. The technology was introduced in the early 1990 s, and has rapidly developed. There have been improvements in resolution, sensitivity and processing speed. There have also been developments in functional processing. OCT angiography is the first application in routine clinical work. PMID:26372783

  4. Glutamatergic Retinal Waves

    PubMed Central

    Kerschensteiner, Daniel

    2016-01-01

    Spontaneous activity patterns propagate through many parts of the developing nervous system and shape the wiring of emerging circuits. Prior to vision, waves of activity originating in the retina propagate through the lateral geniculate nucleus (LGN) of the thalamus to primary visual cortex (V1). Retinal waves have been shown to instruct the wiring of ganglion cell axons in LGN and of thalamocortical axons in V1 via correlation-based plasticity rules. Across species, retinal waves mature in three stereotypic stages (I–III), in which distinct circuit mechanisms give rise to unique activity patterns that serve specific functions in visual system refinement. Here, I review insights into the patterns, mechanisms, and functions of stage III retinal waves, which rely on glutamatergic signaling. As glutamatergic waves spread across the retina, neighboring ganglion cells with opposite light responses (ON vs. OFF) are activated sequentially. Recent studies identified lateral excitatory networks in the inner retina that generate and propagate glutamatergic waves, and vertical inhibitory networks that desynchronize the activity of ON and OFF cells in the wavefront. Stage III wave activity patterns may help segregate axons of ON and OFF ganglion cells in the LGN, and could contribute to the emergence of orientation selectivity in V1. PMID:27242446

  5. Acute Toluene Exposure Alters Expression of Genes in the Central Nervous System Associated With Synaptic Structure and Function

    EPA Science Inventory

    Toluene is a volatile organic compound (VOC) and a ubiquitous air pollutant of interest to EPA regulatory programs. Whereas its acute functional effects are well described, several modes of action in the CNS have been proposed. Therefore, we sought to identify potential pathways ...

  6. Retinal Thickening and Photoreceptor Loss in HIV Eyes without Retinitis

    PubMed Central

    Arcinue, Cheryl A.; Bartsch, Dirk-Uwe; El-Emam, Sharif Y.; Ma, Feiyan; Doede, Aubrey; Sharpsten, Lucie; Gomez, Maria Laura; Freeman, William R.

    2015-01-01

    Purpose To determine the presence of structural changes in HIV retinae (i.e., photoreceptor density and retinal thickness in the macula) compared with age-matched HIV-negative controls. Methods Cohort of patients with known HIV under CART (combination Antiretroviral Therapy) treatment were examined with a flood-illuminated retinal AO camera to assess the cone photoreceptor mosaic and spectral-domain optical coherence tomography (SD-OCT) to assess retinal layers and retinal thickness. Results Twenty-four eyes of 12 patients (n = 6 HIV-positive and 6 HIV-negative) were imaged with the adaptive optics camera. In each of the regions of interest studied (nasal, temporal, superior, inferior), the HIV group had significantly less mean cone photoreceptor density compared with age-matched controls (difference range, 4,308–6,872 cones/mm2). A different subset of forty eyes of 20 patients (n = 10 HIV-positive and 10 HIV-negative) was included in the retinal thickness measurements and retinal layer segmentation with the SD-OCT. We observed significant thickening in HIV positive eyes in the total retinal thickness at the foveal center, and in each of the three horizontal B-scans (through the macular center, superior, and inferior to the fovea). We also noted that the inner retina (combined thickness from ILM through RNFL to GCL layer) was also significantly thickened in all the different locations scanned compared with HIV-negative controls. Conclusion Our present study shows that the cone photoreceptor density is significantly reduced in HIV retinae compared with age-matched controls. HIV retinae also have increased macular retinal thickness that may be caused by inner retinal edema secondary to retinovascular disease in HIV. The interaction of photoreceptors with the aging RPE, as well as possible low-grade ocular inflammation causing diffuse inner retinal edema, may be the key to the progressive vision changes in HIV-positive patients without overt retinitis. PMID:26244973

  7. [Retinal venous obliteration and general pathology].

    PubMed

    Aconiu, M; Mihălaş, G; Nemoianu, C

    1992-01-01

    The study of 148 retinal venous obliterations have shown 81 occlusions of central vein and 67 of I and II venous branch. A number of 90 was for the feminine gender (sex) and 59 for the masculine sex. The average age for the appearance of the venous occlusions was 62 years old, having extreme limits between 36-84 years old. Bilaterality has been for 3 cases. Concerning the associated medical affections, hypertension was for 67 patients, myocardiosclerosis have been mentioned for 67 patients, atherosclerosis for 21 patients, pulmonary scleroemphisis for 12 patients. Arterial hypertension with its aspersion that is arteriosclerosis are the main factors that have generated retinal circulation modifyings and have led to a degree of arterial insufficiency. Comparing the ophthalmological aspect to the pressure in the ophthalmic artery, most of the patients had a concordance of TACR and the retinal and choroidal angiosclerosis. The oscillometric examination to the inferior members has been effectuated for 21 patients and it has shown diminished values only for 3 cases. The forecast of the disease is still reserved. Following a group of 40 patients having OVR between 5 and 15 years old it has been established an average survival of 6.2 years. It is mentioned that 26% between these have dyed during the first six years. PMID:1520668

  8. Photodynamic therapy and anti-vascular endothelial growth factor for acute central serous chorioretinopathy: a systematic review and meta-analysis.

    PubMed

    Lu, H Q; Wang, E Q; Zhang, T; Chen, Y X

    2016-01-01

    This systematic review aims to update current evidence on the efficacy and safety of photodynamic therapy (PDT) and anti-vascular endothelial growth factor (anti-VEGF) injections for acute central serous chorioretinopathy (CSC). A comprehensive literature search was conducted in PubMed, EMBASE, and Cochrane Library. Studies comparing (1) PDT versus placebo, (2) anti-VEGF versus placebo, and (3) PDT versus anti-VEGF were included and meta-analyzes were performed when appropriate. Ocular and systemic adverse effects were also summarized. Literature search yielded six comparative studies, among which five were included for this review. Meta-analysis with three studies indicated that eyes treated with PDT achieved better best-corrected visual acuity (BCVA) and central macular thickness (CMT) than the placebo group throughout a follow-up of 12 months. Meta-analysis with another two studies comparing anti-VEGF injections and placebo showed that BCVA at first month was better in anti-VEGF group than in placebo group, though the differences of BCVA and CMT no longer existed at 3 and 6 months after injection. There was no report directly comparing PDT and anti-VEGF for acute CSC. No severe complications was reported in included studies. In this review, current evidence suggested that early treatment of acute CSC by PDT is valuable in improving visual acuity, reducing subretinal fluid, and maintaining long term effectiveness. Anti-VEGF injection could shorten the duration of symptoms and accelerate visual improvement at early stage of disease. Direct comparison between these two treatment will be needed in the future. PMID:26514243

  9. Retinal Failure in Diabetes: a Feature of Retinal Sensory Neuropathy.

    PubMed

    Gray, Ellyn J; Gardner, Thomas W

    2015-12-01

    Physiologic adaptations mediate normal responses to short-term and long-term stresses to ensure organ function. Organ failure results if adaptive responses fail to resolve persistent stresses or maladaptive reactions develop. The retinal neurovascular unit likewise undergoes adaptive responses to diabetes resulting in a retinal sensory neuropathy analogous to other sensory neuropathies. Vision-threatening diabetic retinal neuropathy results from unremitting metabolic and inflammatory stresses, leading to macular edema and proliferative diabetic retinopathy, states of "retinal failure." Current regulatory strategies focus primarily on the retinal failure stages, but new diagnostic modalities and understanding of the pathophysiology of diabetic retinopathy may facilitate earlier treatment to maintain vision in persons with diabetes. PMID:26458378

  10. Perceptual Fading without Retinal Adaptation

    ERIC Educational Resources Information Center

    Hsieh, Po-Jang; Colas, Jaron T.

    2012-01-01

    A retinally stabilized object readily undergoes perceptual fading and disappears from consciousness. This startling phenomenon is commonly believed to arise from local bottom-up sensory adaptation to edge information that occurs early in the visual pathway, such as in the lateral geniculate nucleus of the thalamus or retinal ganglion cells. Here…

  11. High resolution optoelectronic retinal prosthesis

    NASA Astrophysics Data System (ADS)

    Loudin, Jim; Dinyari, Rostam; Huie, Phil; Butterwick, Alex; Peumans, Peter; Palanker, Daniel

    2009-02-01

    Electronic retinal prostheses seek to restore sight in patients with retinal degeneration by delivering pulsed electric currents to retinal neurons via an array of microelectrodes. Most implants use inductive or optical transmission of information and power to an intraocular receiver, with decoded signals subsequently distributed to retinal electrodes through an intraocular cable. Surgical complexity could be minimized by an "integrated" prosthesis, in which both power and data are delivered directly to the stimulating array without any discrete components or cables. We present here an integrated retinal prosthesis system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a video goggle projection system operating at near-infrared wavelengths (~ 900 nm). Photodiodes convert light into pulsed electric current, with charge injection maximized by specially optimized series photodiode circuits. Prostheses of three different pixel densities (16 pix/mm2, 64 pix/mm2, and 256 pix/mm2) have been designed, simulated, and prototyped. Retinal tissue response to subretinal implants made of various materials has been investigated in RCS rats. The resulting prosthesis can provide sufficient charge injection for high resolution retinal stimulation without the need for implantation of any bulky discrete elements such as coils or tethers. In addition, since every pixel functions independently, pixel arrays may be placed separately in the subretinal space, providing visual stimulation to a larger field of view.

  12. Retinal Imaging and Image Analysis

    PubMed Central

    Abràmoff, Michael D.; Garvin, Mona K.; Sonka, Milan

    2011-01-01

    Many important eye diseases as well as systemic diseases manifest themselves in the retina. While a number of other anatomical structures contribute to the process of vision, this review focuses on retinal imaging and image analysis. Following a brief overview of the most prevalent causes of blindness in the industrialized world that includes age-related macular degeneration, diabetic retinopathy, and glaucoma, the review is devoted to retinal imaging and image analysis methods and their clinical implications. Methods for 2-D fundus imaging and techniques for 3-D optical coherence tomography (OCT) imaging are reviewed. Special attention is given to quantitative techniques for analysis of fundus photographs with a focus on clinically relevant assessment of retinal vasculature, identification of retinal lesions, assessment of optic nerve head (ONH) shape, building retinal atlases, and to automated methods for population screening for retinal diseases. A separate section is devoted to 3-D analysis of OCT images, describing methods for segmentation and analysis of retinal layers, retinal vasculature, and 2-D/3-D detection of symptomatic exudate-associated derangements, as well as to OCT-based analysis of ONH morphology and shape. Throughout the paper, aspects of image acquisition, image analysis, and clinical relevance are treated together considering their mutually interlinked relationships. PMID:21743764

  13. Quantitative analysis of retinal OCT.

    PubMed

    Sonka, Milan; Abràmoff, Michael D

    2016-10-01

    Clinical acceptance of 3-D OCT retinal imaging brought rapid development of quantitative 3-D analysis of retinal layers, vasculature, retinal lesions as well as facilitated new research in retinal diseases. One of the cornerstones of many such analyses is segmentation and thickness quantification of retinal layers and the choroid, with an inherently 3-D simultaneous multi-layer LOGISMOS (Layered Optimal Graph Image Segmentation for Multiple Objects and Surfaces) segmentation approach being extremely well suited for the task. Once retinal layers are segmented, regional thickness, brightness, or texture-based indices of individual layers can be easily determined and thus contribute to our understanding of retinal or optic nerve head (ONH) disease processes and can be employed for determination of disease status, treatment responses, visual function, etc. Out of many applications, examples provided in this paper focus on image-guided therapy and outcome prediction in age-related macular degeneration and on assessing visual function from retinal layer structure in glaucoma. PMID:27503080

  14. [Intrinsically Photosensitive Retinal Ganglion Cells].

    PubMed

    Skorkovská, K; Skorkovská, Š

    2015-06-01

    Recently discovered intrinsically photosensitive melanopsin-containing retinal ganglion cells contribute to circadian photoentrainment and pupillary constriction; recent works have also brought new evidence for their accessory role in the visual system in humans. Pupil light reaction driven by individual photoreceptors can be isolated by means of the so called chromatic pupillography. The use of chromatic stimuli to elicit different pupillary responses may become an objective clinical pupil test in the detection of retinal diseases and in assessing new therapeutic approaches particularly in hereditary retinal degenerations like retinitis pigmentosa. In advanced stages of disease, the pupil light reaction is even more sensitive than standard electroretinography for detecting residual levels of photoreceptor activity. This review summarizes current knowledge on intrinsically photosensitive retinal cells and highlights its possible implications for clinical practice. PMID:26201360

  15. Retinal connectivity and primate vision

    PubMed Central

    Lee, Barry B.; Martin, Paul R.; Grünert, Ulrike

    2012-01-01

    The general principles of retinal organization are now well known. It may seem surprising that retinal organization in the primate, which has a complex visual behavioral repertoire, appears relatively simple. In this review, we primarily consider retinal structure and function in primate species. Photoreceptor distribution and connectivity are considered as are connectivity in the outer and inner retina. One key issue is the specificity of retinal connections; we suggest that the retina shows connectional specificity but this is seldom complete, and we consider here the functional consequences of imprecise wiring. Finally, we consider how retinal systems can be linked to psychophysical descriptions of different channels, chromatic and luminance, which are proposed to exist in the primate visual system. PMID:20826226

  16. Retinal connectivity and primate vision.

    PubMed

    Lee, Barry B; Martin, Paul R; Grünert, Ulrike

    2010-11-01

    The general principles of retinal organization are now well known. It may seem surprising that retinal organization in the primate, which has a complex visual behavioral repertoire, appears relatively simple. In this review, we primarily consider retinal structure and function in primate species. Photoreceptor distribution and connectivity are considered as are connectivity in the outer and inner retina. One key issue is the specificity of retinal connections; we suggest that the retina shows connectional specificity but this is seldom complete, and we consider here the functional consequences of imprecise wiring. Finally, we consider how retinal systems can be linked to psychophysical descriptions of different channels, chromatic and luminance, which are proposed to exist in the primate visual system. PMID:20826226

  17. [Multifocal Vitelliform Retinal Lesion].

    PubMed

    Streicher, T; Špirková, J; Ilavská, M

    2015-06-01

    The authors present retrospective follow up of patient with bilateral multifocal vitelliform retinal lesion during the 18 years period. At this time, spontaneous improvement of objective picture on retina and subjective visual troubles was observed. It is probable, that this case is a part of the same symptom complex as a variant of Best´s hereditary disease. This conclusion was based on initial stadium of phenotypical expressivity and additional evaluations. The course and outcomes of visual functions were different. The hereditary transmission was not confirmed. PMID:26201364

  18. Amyloidosis in Retinal Neurodegenerative Diseases.

    PubMed

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer's disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer's patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer's patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a "window" to the brain. PMID:27551275

  19. Amyloidosis in Retinal Neurodegenerative Diseases

    PubMed Central

    Masuzzo, Ambra; Dinet, Virginie; Cavanagh, Chelsea; Mascarelli, Frederic; Krantic, Slavica

    2016-01-01

    As a part of the central nervous system, the retina may reflect both physiological processes and abnormalities related to pathologies that affect the brain. Amyloidosis due to the accumulation of amyloid-beta (Aβ) was initially regarded as a specific and exclusive characteristic of neurodegenerative alterations seen in the brain of Alzheimer’s disease (AD) patients. More recently, it was discovered that amyloidosis-related alterations, similar to those seen in the brain of Alzheimer’s patients, also occur in the retina. Remarkably, these alterations were identified not only in primary retinal pathologies, such as age-related macular degeneration (AMD) and glaucoma, but also in the retinas of Alzheimer’s patients. In this review, we first briefly discuss the biogenesis of Aβ, a peptide involved in amyloidosis. We then discuss some pathological aspects (synaptic dysfunction, mitochondrial failure, glial activation, and vascular abnormalities) related to the neurotoxic effects of Aβ. We finally highlight common features shared by AD, AMD, and glaucoma in the context of Aβ amyloidosis and further discuss why the retina, due to the transparency of the eye, can be considered as a “window” to the brain. PMID:27551275

  20. Pregnancy-associated retinal diseases and their management.

    PubMed

    Errera, Marie-Hélène; Kohly, Radha P; da Cruz, Lyndon

    2013-01-01

    Pregnancy-associated retinal diseases are conditions that may occur uniquely in pregnancy or, more commonly, general conditions that may worsen or alter during pregnancy as a result of hematologic, hormonal, metabolic, cardiovascular, and immunologic changes. Diabetic retinopathy (DR) is by far the most common retinal condition that is altered by pregnancy. However, there are currently no widely accepted, precise clinical guidelines regarding its management during pregnancy. At present it is not possible to predict who will regress and who will progress without treatment. Some of the variation in progression of DR in pregnancy may be a result of well-known risk factors such as hypertension or inadequate glycemic control prior to pregnancy. Other pregnancy-associated retinal diseases are relatively uncommon, and their treatments are poorly characterized. Pre-existing conditions include the white dot syndromes, such as punctuate inner choroidopathy and ocular histoplasmosis syndrome, as well as chorioretinal neovascularization from many other etiologies. Retinal and chorioretinal disorders that can arise during pregnancy include central serous chorioretinopathy and occlusive vasculopathy such as retinal artery occlusion (Purtschers-like retinopathy) and retinal vein occlusion. There remains a small group that appear to be unique to pregnancy, with pre-eclampsia- and eclampsia-associated retinopathy, disseminated intravascular coagulopathy, or amniotic fluid embolism being the best described. In angiogenic retinal diseases outside of pregnancy, the use of anti-vascular endothelial growth factor (anti-VEGF agents) has proven helpful. There are no safety data about the use of anti-VEGF agents during pregnancy, and conventionally the proposed interventions have been laser photocoagulation and systemic or intravitreal injections of steroids. Most of the literature on the treatment of pregnancy associated-chorioretinal neovascularization is anecdotal. PMID:23410822

  1. Decorrelation and efficient coding by retinal ganglion cells

    PubMed Central

    Pitkow, Xaq; Meister, Markus

    2013-01-01

    An influential theory of visual processing asserts that retinal center-surround receptive fields remove spatial correlations in the visual world, producing ganglion cell spike trains that are less redundant than the corresponding image pixels. For bright, high-contrast images, this decorrelation would enhance coding efficiency in optic nerve fibers of limited capacity. Here we test the central prediction of the theory and demonstrate that the spike trains of retinal ganglion cells are indeed decorrelated compared to the visual input. However, most of the decorrelation is accomplished not by the receptive fields, but by nonlinear processing in the retina. We show that a steep response threshold enhances efficient coding by noisy spike trains, and the effect of this nonlinearity is near optimal in both salamander and macaque retina. These results offer an explanation for the sparseness of retinal spike trains, and highlight the importance of treating the full nonlinear character of neural codes. PMID:22406548

  2. [Treatment of serous macular retinal detachment with antihistamines].

    PubMed

    Kirschfeld, K

    2015-01-01

    The etiology of retinal detachment in central serous retinopathy (CSR) is unknown; however, three facts are generally accepted: (1) the serous exudate which raises the layers of the receptors/pigment epithelium is formed due to hyperpermeability in the choriocapillaries, (2) patients frequently suffer from headaches and (3) stress promotes the incidence of CSR. A high blood plasma histamine concentration can cause the abovementioned symptoms which suggests that histamine might provoke CSR. Within 1 week after administration of the antihistamine loratadin a considerable reduction in the retinal exudate and restoration of vision were observed. This supports the hypothesis that histamine could be involved in the process of retinal detachment. Further investigations and large scale clinical trials should clarify if this hypothesis can be proved or disproved and whether antihistamines can be used for age-related macular degeneration (AMD). PMID:25278347

  3. The Role of the Endothelin System in the Vascular Dysregulation Involved in Retinitis Pigmentosa

    PubMed Central

    Sorrentino, Francesco Saverio; Bonifazzi, Claudio; Perri, Paolo

    2015-01-01

    Retinitis pigmentosa is a clinical and genetic group of inherited retinal disorders characterized by alterations of photoreceptors and retinal pigment epithelium leading to a progressive concentric visual field restriction, which may bring about severe central vision impairment. Haemodynamic studies in patients with retinitis pigmentosa have demonstrated ocular blood flow abnormalities both in retina-choroidal and in retroocular vascular system. Moreover, several investigations have studied the augmentation of endothelin-1 plasma levels systemically in the body and locally in the eye. This might account for vasoconstriction and ischemia, typical in vascular dysregulation syndrome, which can be considered an important factor of reduction of the ocular blood flow in subjects affected by retinitis pigmentosa. PMID:26613048

  4. White Matter Consequences of Retinal Receptor and Ganglion Cell Damage

    PubMed Central

    Ogawa, Shumpei; Takemura, Hiromasa; Horiguchi, Hiroshi; Terao, Masahiko; Haji, Tomoki; Pestilli, Franco; Yeatman, Jason D.; Tsuneoka, Hiroshi; Wandell, Brian A.; Masuda, Yoichiro

    2014-01-01

    Purpose. Patients with Leber hereditary optic neuropathy (LHON) and cone-rod dystrophy (CRD) have central vision loss; but CRD damages the retinal photoreceptor layer, and LHON damages the retinal ganglion cell (RGC) layer. Using diffusion MRI, we measured how these two types of retinal damage affect the optic tract (ganglion cell axons) and optic radiation (geniculo-striate axons). Methods. Adult onset CRD (n = 5), LHON (n = 6), and healthy controls (n = 14) participated in the study. We used probabilistic fiber tractography to identify the optic tract and the optic radiation. We compared axial and radial diffusivity at many positions along the optic tract and the optic radiation. Results. In both types of patients, diffusion measures within the optic tract and the optic radiation differ from controls. The optic tract change is principally a decrease in axial diffusivity; the optic radiation change is principally an increase in radial diffusivity. Conclusions. Both photoreceptor layer (CRD) and retinal ganglion cell (LHON) retinal disease causes substantial change in the visual white matter. These changes can be measured using diffusion MRI. The diffusion changes measured in the optic tract and the optic radiation differ, suggesting that they are caused by different biological mechanisms. PMID:25257055

  5. Comparison of centrally injected tryptophan-related substances inducing sedation in acute isolation stress-induced neonatal chicks.

    PubMed

    Yoshida, Junki; Erwan, Edi; Chowdhury, Vishwajit Sur; Ogino, Yumi; Shigemura, Asako; Denbow, D Michael; Furuse, Mitsuhiro

    2015-02-01

    In the present study, we first focused on the function of l-tryptophan (TRP) metabolites which are synthesized in different metabolic pathways, namely, the kynurenine (KYN) pathway and serotonin (5-HT) pathway during an acute isolation stress. When l-TRP metabolites were intracerebroventricularly injected on an equimolar basis (100 nmol), 5-HT induced a sedative effect in neonatal chicks. Additionally, plasma corticosterone, dopamine, 5-HT, and its metabolite 5-hydroxyindoleacetic acid concentrations were increased in the diencephalon of the 5-HT treated group compared with other groups. Second, the two doses (400 or 800 nmol) of l- and d-TRP were compared under a corticotrophin-releasing hormone-augmented social isolation stress. When comparing the efficacy between l- and d-TRP against stress behavior, both amino acids had a similar effect and quickly suppressed distress vocalizations. Finally, d-amino acid levels in the diencephalon and telencephalon were measured but d-TRP was not found. These results indicate that l- and d-TRP induce the same effect in attenuating stress but the mode of action of TRP derivatives, namely 5-HT differs during an acute isolation stress in neonatal chick. The absence of d-TRP in the diencephalon further suggests that instead of being an endogenous factor it may play role as a pharmacological factor. PMID:25459103

  6. Inhibition of cyclophilin D by cyclosporin A promotes retinal ganglion cell survival by preventing mitochondrial alteration in ischemic injury

    PubMed Central

    Kim, S Y; Shim, M S; Kim, K-Y; Weinreb, R N; Wheeler, L A; Ju, W-K

    2014-01-01

    Cyclosporin A (CsA) inhibits the opening of the mitochondrial permeability transition pore (MPTP) by interacting with cyclophilin D (CypD) and ameliorates neuronal cell death in the central nervous system against ischemic injury. However, the molecular mechanisms underlying CypD/MPTP opening-mediated cell death in ischemic retinal injury induced by acute intraocular pressure (IOP) elevation remain unknown. We observed the first direct evidence that acute IOP elevation significantly upregulated CypD protein expression in ischemic retina at 12 h. However, CsA prevented the upregulation of CypD protein expression and promoted retinal ganglion cell (RGC) survival against ischemic injury. Moreover, CsA blocked apoptotic cell death by decreasing cleaved caspase-3 protein expression in ischemic retina. Of interest, although the expression level of Bcl-xL protein did not show a significant change in ischemic retina treated with vehicle or CsA at 12 h, ischemic damage induced the reduction of Bcl-xL immunoreactivity in RGCs. More importantly, CsA preserved Bcl-xL immunoreactivity in RGCs of ischemic retina. In parallel, acute IOP elevation significantly increased phosphorylated Bad (pBad) at Ser112 protein expression in ischemic retina at 12 h. However, CsA significantly preserved pBad protein expression in ischemic retina. Finally, acute IOP elevation significantly increased mitochondrial transcription factor A (Tfam) protein expression in ischemic retina at 12 h. However, CsA significantly preserved Tfam protein expression in ischemic retina. Studies on mitochondrial DNA (mtDNA) content in ischemic retina showed that there were no statistically significant differences in mtDNA content among control and ischemic groups treated with vehicle or CsA. Therefore, these results provide evidence that the activation of CypD-mediated MPTP opening is associated with the apoptotic pathway and the mitochondrial alteration in RGC death of ischemic retinal injury. On the basis

  7. Blood Pressure Modifies Retinal Susceptibility to Intraocular Pressure Elevation

    PubMed Central

    He, Zheng; Nguyen, Christine T. O.; Armitage, James A.; Vingrys, Algis J.; Bui, Bang V.

    2012-01-01

    Primary open angle glaucoma affects more than 67 million people. Elevated intraocular pressure (IOP) is a risk factor for glaucoma and may reduce nutrient availability by decreasing ocular perfusion pressure (OPP). An interaction between arterial blood pressure and IOP determines OPP; but the exact contribution that these factors have for retinal function is not fully understood. Here we sought to determine how acute modifications of arterial pressure will affect the susceptibility of neuronal function and blood flow to IOP challenge. Anaesthetized (ketamine:xylazine) Long-Evan rats with low (∼60 mmHg, sodium nitroprusside infusion), moderate (∼100 mmHg, saline), or high levels (∼160 mmHg, angiotensin II) of mean arterial pressure (MAP, n = 5–10 per group) were subjected to IOP challenge (10–120 mmHg, 5 mmHg steps every 3 minutes). Electroretinograms were measured at each IOP step to assess bipolar cell (b-wave) and inner retinal function (scotopic threshold response or STR). Ocular blood flow was measured using laser-Doppler flowmetry in groups with similar MAP level and the same IOP challenge protocol. Both b-wave and STR amplitudes decreased with IOP elevation. Retinal function was less susceptible to IOP challenge when MAP was high, whereas the converse was true for low MAP. Consistent with the effects on retinal function, higher IOP was needed to attenuated ocular blood flow in animals with higher MAP. The susceptibility of retinal function to IOP challenge can be ameliorated by acute high BP, and exacerbated by low BP. This is partially mediated by modifications in ocular blood flow. PMID:22359566

  8. Concurrent hypopituitarism and leukemic retinopathy in a child with B-precursor acute lymphoblastic leukemia and isolated central nervous system relapse

    PubMed Central

    Wu, K.H.; Wu, H.P.; Lin, H.J.; Wang, C.H.; Chen, H.Y.; Weng, T.; Peng, C.T.; Chao, Y.H.

    2016-01-01

    Hypopituitarism in leukemia is very rare. In addition, central nervous system (cns) relapse and leukemic retinopathy in childhood acute lymphoblastic leukemia (all) have declined with the use of modern systemic chemotherapy that includes cns prophylaxis. Here, we report the case of a 4-year-old girl who received chemotherapy and intrathecal therapy without cns radiation after a diagnosis of B-precursor all without cns involvement. Three months after chemotherapy completion, she presented with lower-extremity weakness and was diagnosed with an isolated cns relapse. Concurrent hypopituitarism and leukemic retinopathy were also found. After receiving craniospinal radiotherapy and systemic chemotherapy, her retinopathy and vision improved. She is now in complete remission, and she is still on chemotherapy according to the guideline from the Pediatric Oncology Group. Although rare, hypopituitarism and leukemic retinopathy should be taken into consideration in patients with cns involvement by leukemia. PMID:27536191

  9. [The effect of transcardiac galvanization on the size of the necrotic mass and on the central hemodynamic indices in patients with an acute myocardial infarct].

    PubMed

    Maslov, A G; Karpov, R S; Metelkin, A V; Lychev, V G; Vidiakov, G E; Shishkin, M S; Timofeev, A V; Derzoglo, G D

    1994-01-01

    The authors examined 110 males and females admitted to hospital within 6 hours since the onset of new macrofocal anterior myocardial infarction running without complications. All the patients underwent transcardiac galvanization (TG) in the initial disease hours. Precardiac mapping, tetrapolar rheography and clinical observation provided evidence on TG course action on the necrosis mass, central hemodynamics and clinical appearance of the disease in the acute and postinfarction periods. TG promoted faster and more marked improvement of cardiac muscle contractility, attaining higher functional level of inotropic myocardial activity up to the disease month 6. This was associated with alleviation of circulatory disorders both at the hospital and postinfarction stage. The response to course TG results from cardioprotective action of constant electric current on ischemic myocardium which limits the zone of the lesion thus reducing early fatal cases number and preventing cardiogenic shock. PMID:7985146

  10. Selective retinal therapy with a continuous line scanning laser

    NASA Astrophysics Data System (ADS)

    Paulus, Yannis M.; Jain, ATul; Gariano, Ray F.; Nomoto, Hiroyuki; Schuele, Georg; Sramek, Christopher; Charalel, Resmi; Palanker, Daniel

    2010-02-01

    This study evaluates the effects of exposure duration, beam diameter, and power on the safety, selectivity, and healing of retinal lesions created using a continuous line scanning laser. A 532 nm laser (PASCALTM) with retinal beam diameters of 40 and 66 μm was applied to 60 eyes of 30 Dutch-Belted rabbits. Retinal exposure duration varied from 15 to 60 μs. Lesions were acutely assessed by ophthalmoscopy and fluorescein angiography (FA). RPE flatmounts were evaluated with live-dead fluorescent assay (LD). Histological analysis was performed at 1 hour, 1 and 3 days, 1 and 2 weeks, and 1 and 2 months following laser treatment. Ophthalmoscopic visibility (OV) of the lesions corresponded to photoreceptor damage on histological analysis at 1 hour. In subvisible lesions, FA and LD yielded similar thresholds of RPE damage. The ratios of the threshold of rupture and of OV to FA visibility (measures of safety and selectivity) increased with decreasing duration and beam diameter. Above the threshold of OV, histology showed focal RPE damage and photoreceptor loss at one day without inner retinal effects. By one week, continuity of photoreceptor and RPE layers was restored. By 1 month, photoreceptors appeared normal while hypertrophy and hyperpigmentation of the RPE persisted. Retinal therapy with a fast scanning continuous laser achieves selective targeting of the RPE and, at higher power, of the photoreceptors. The damage zone in the photoreceptor layer is quickly filled-in, likely due to photoreceptor migration from adjacent zones. Continuous scanning laser can treat large retinal areas within standard eye fixation time.

  11. Central Agonism of GPR120 Acutely Inhibits Food Intake and Food Reward and Chronically Suppresses Anxiety-Like Behavior in Mice

    PubMed Central

    Fisette, Alexandre; Fernandes, Maria F.; Hryhorczuk, Cécile; Poitout, Vincent; Alquier, Thierry; Fulton, Stephanie

    2016-01-01

    Background: GPR120 (FFAR4) is a G-protein coupled receptor implicated in the development of obesity and the antiinflammatory and insulin-sensitizing effects of omega-3 (ω-3) polyunsaturated fatty acids. Increasing central ω-3 polyunsaturated fatty acid levels has been shown to have both anorectic and anxiolytic actions. Despite the strong clinical interest in GPR120, its role in the brain is largely unknown, and thus we sought to determine the impact of central GPR120 pharmacological activation on energy balance, food reward, and anxiety-like behavior. Methods: Male C57Bl/6 mice with intracerebroventricular cannulae received a single injection (0.1 or 1 µM) or continuous 2-week infusion (1 µM/d; mini-pump) of a GPR120 agonist or vehicle. Free-feeding intake, operant lever-pressing for palatable food, energy expenditure (indirect calorimetry), and body weight were measured. GPR120 mRNA expression was measured in pertinent brain areas. Anxiety-like behavior was assessed in the elevated-plus maze and open field test. Results: GPR120 agonist injections substantially reduced chow intake during 4 hours postinjection, suppressed the rewarding effects of high-fat/-sugar food, and blunted approach-avoidance behavior in the open field. Conversely, prolonged central GPR120 agonist infusions reduced anxiety-like behavior in the elevated-plus maze and open field, yet failed to affect free-feeding intake, energy expenditure, and body weight on a high-fat diet. Conclusion: Acute reductions in food intake and food reward suggest that GPR120 could mediate the effects of central ω-3 polyunsaturated fatty acids to inhibit appetite. The anxiolytic effect elicited by GPR120 agonist infusions favors the testing of compounds that can enter the brain to activate GPR120 for the mitigation of anxiety. PMID:26888796

  12. Glucagon-like peptide-1 does not have acute effects on central or renal hemodynamics in patients with type 2 diabetes without nephropathy.

    PubMed

    Asmar, Ali; Simonsen, Lene; Asmar, Meena; Madsbad, Sten; Holst, Jens J; Frandsen, Erik; Moro, Cedric; Sorensen, Charlotte M; Jonassen, Thomas; Bülow, Jens

    2016-05-01

    During acute administration of native glucagon-like peptide-1 (GLP-1), we previously demonstrated central hemodynamic effects in healthy males, whereas renal hemodynamics, despite renal uptake of GLP-1 in excess of glomerular filtration, was unaffected. In the present study, we studied hemodynamic effects of GLP-1 in patients with type 2 diabetes under fixed sodium intake. During a 3-h infusion of GLP-1 (1.5 pmol·kg(-1)·min(-1)) or saline, intra-arterial blood pressure and heart rate were measured continuously, concomitantly with cardiac output estimated by pulse contour analysis. Renal plasma flow, glomerular filtration rate, and uptake/release of hormones and ions were measured using Fick's Principle after catheterization of a renal vein. Urine collection was conducted throughout the experiments at voluntary voiding, and patients remained supine during the experiments. During the GLP-1 infusion, systolic and diastolic blood pressure and cardiac output remained unchanged, whereas heart rate increased significantly. Arterio-venous gradients for GLP-1 exceeded glomerular filtrations significantly, but renal plasma flow and glomerular filtration rate as well as renal sodium and lithium excretion were not affected. In conclusion, acute administration of GLP-1 in patients with type 2 diabetes leads to a positive chronotropic effect, but in contrast to healthy individuals, cardiac output does not increase in patients with type 2 diabetes. Renal hemodynamics and sodium excretion are not affected. PMID:26956188

  13. Adenosine triphosphate-induced photoreceptor death and retinal remodeling in rats

    PubMed Central

    Vessey, Kirstan A; Greferath, Ursula; Aplin, Felix P; Jobling, Andrew I; Phipps, Joanna A; Ho, Tracy; De Iongh, Robbert U; Fletcher, Erica L

    2014-01-01

    Many common causes of blindness involve the death of retinal photoreceptors, followed by progressive inner retinal cell remodeling. For an inducible model of retinal degeneration to be useful, it must recapitulate these changes. Intravitreal administration of adenosine triphosphate (ATP) has recently been found to induce acute photoreceptor death. The aim of this study was to characterize the chronic effects of ATP on retinal integrity. Five-week-old, dark agouti rats were administered 50 mM ATP into the vitreous of one eye and saline into the other. Vision was assessed using the electroretinogram and optokinetic response and retinal morphology investigated via histology. ATP caused significant loss of visual function within 1 day and loss of 50% of the photoreceptors within 1 week. At 3 months, 80% of photoreceptor nuclei were lost, and total photoreceptor loss occurred by 6 months. The degeneration and remodeling were similar to those found in heritable retinal dystrophies and age-related macular degeneration and included inner retinal neuronal loss, migration, and formation of new synapses; Müller cell gliosis, migration, and scarring; blood vessel loss; and retinal pigment epithelium migration. In addition, extreme degeneration and remodeling events, such as neuronal and glial migration outside the neural retina and proliferative changes in glial cells, were observed. These extreme changes were also observed in the 2-year-old P23H rhodopsin transgenic rat model of retinitis pigmentosa. This ATP-induced model of retinal degeneration may provide a valuable tool for developing pharmaceutical therapies or for testing electronic implants aimed at restoring vision. J. Comp. Neurol. 522:2928–2950, 2014. © 2014 Wiley Periodicals, Inc. PMID:24639102

  14. Relationship between retinal vascular occlusions and incident cerebrovascular diseases: A systematic review and meta-analysis.

    PubMed

    Zhou, Yue; Zhu, Wengen; Wang, Changyun

    2016-06-01

    Several studies investigating the role of retinal vascular occlusions, on cerebrovascular diseases (CVD) have been reported, but the results are still inconsistent. We therefore sought to evaluate the relationship between retinal vascular occlusions and CVD.We systematically searched the Cochrane Library, PubMed, and ScienceDirect databases through January 31, 2016 for studies evaluating the effect of retinal vascular occlusions on the risk of CVD. Data were abstracted using predefined criteria, and then pooled by RevMan 5.3 software.A total of 9 retrospective studies were included in this meta-analysis. When compared with individuals without retinal vascular occlusions, both individuals with retinal artery occlusion (RAO) (odds ratio [OR] = 2.01, 95% confidence interval [CI]: 1.21-3.34; P = 0.005) and individuals with retinal vein occlusion (RVO) (OR = 1.37, 95% CI: 1.24-1.50; P < 0.00001) had higher risks of developing CVD. Additionally, both individuals with central retinal artery occlusion (CRAO) (OR = 2.00, 95% CI: 1.12-3.56; P = 0.02) and branch retinal artery occlusion (BRAO) (OR = 1.60, 95% CI: 1.03-1.48; P = 0.04) were significantly associated with increased risk of CVD.Published literatures support both RVO and RAO are associated with increased risks of CVD. Further prospective studies are needed to confirm these findings. PMID:27368050

  15. Multimodal retinal imaging of diabetic macular edema: toward new paradigms of pathophysiology.

    PubMed

    Midena, Edoardo; Bini, Silvia

    2016-09-01

    The pathophysiology of diabetic macular edema (DME) is multifactorial and partly still unknown. An increasing body of evidence suggests that neurodegeneration and retinal glial cells activation occur even before the earliest clinical manifestation of diabetic retinal vasculopathy. Nowadays, new non-invasive techniques are available to assess and characterize DME, not only in a quantitative perspective, but also making it possible to understand and quantify the pathogenic processes sustaining fluid accumulation. Optical coherence tomography (OCT) allows documenting not only parameters such as macular volume, central and sectorial retinal thickness, fluid localization, and integrity of retinal layers, but also new still poorly investigated reflectivity aspects. Hyperreflective intraretinal spots (HRS) have been detected on OCT scans through the retinal layers, with a presumptive migration pattern towards the external layers during the occurrence of diabetic retinopathy and DME. These HRS have been hypothesised to represent an in-vivo marker of microglial activation. Autofluorescence of the fundus (FAF) also offers a non-invasive imaging technique of DME. The area of increased FAF correlates with the presence of intraretinal fluid and probably retinal glial activation. Microperimetry allows the measurement of retinal sensitivity by testing specific selected retinal areas. Some studies have shown that increased macular FAF in DME correlates better with visual function assessed with microperimetry than with visual acuity, showing that new imaging and functional techniques may help to elucidate DME pathogenesis and to target therapeutical strategies. PMID:27154296

  16. PIMASERTIB AND SEROUS RETINAL DETACHMENTS

    PubMed Central

    AlAli, Alaa; Bushehri, Ahmad; Park, Jonathan C.; Krema, Hatem

    2016-01-01

    Purpose: To report a case of multifocal serous retinal detachments associated with pimasertib. Methods: The authors report a 26-year-old patient who developed bilateral multifocal serous retinal detachments appearing 2 days after starting pimasertib (as part of a clinical trial investigating its use in low-grade metastatic ovarian cancer) and rapidly resolving 3 days after stopping it. Conclusion: The mechanism of MEK inhibitor induced visual toxicity remains unclear. The pathophysiology of multifocal serous retinal detachments as a complication of pimasertib is still poorly understood. PMID:26444523

  17. Vitreal Ocygenation in Retinal Ischemia Reperfusion

    SciTech Connect

    Abdallab, Walid; AmeriMD, Hossein; Barron, Ernesto; ChaderPhD, Gerald; Greenbaum, Elias; Hinton, David E; Humayun, Mark S

    2011-01-01

    PURPOSE. To study the feasibility of anterior vitreal oxygenation for the treatment of acute retinal ischemia. METHODS. Twenty rabbits were randomized into an oxygenation group, a sham treatment group, and a no treatment group. Baseline electroretinography (ERG) and preretinal oxygen (PO2) measurements were obtained 3 to 5 days before surgery. Intraocular pressure was raised to 100 mm Hg for 90 minutes and then normalized. The oxygenation group underwent vitreal oxygenation for 30 minutes using intravitreal electrodes. The sham treatment group received inactive electrodes for 30 minutes while there was no intervention for the no treatment group. Preretinal PO2 in the posterior vitreous was measured 30 minutes after intervention or 30 minutes after reperfusion (no treatment group) and on postoperative days (d) 3, 6, 9, and 12. On d14, rabbits underwent ERG and were euthanatized.

  18. Retinal development in the gilthead seabream Sparus aurata.

    PubMed

    Pavón-Muñoz, T; Bejarano-Escobar, R; Blasco, M; Martín-Partido, G; Francisco-Morcillo, J

    2016-02-01

    The retinal development of the gilthead seabream Sparus aurata has been analysed from late embryonic development to juvenile stages using classical histological and immunohistological methods. Five significant phases were established. Phases 1 and 2 comprise the late embryonic and hatching stages, respectively. The results indicate that during these early stages the retina is composed of a single neuroblastic layer that consists of undifferentiated retinal progenitor cells. Phase 3 (late prolarval stage) is characterized by the emergence of the retinal layers and the appearance of neurochemical profiles in differentiating photoreceptors, amacrine and ganglion cells. Phases 4 and 5 comprise the late larval and juvenile stages. In these stages, all the retinal cell types can be detected immunohistochemically. All the maturational events described are first detected in the central retina and, as development progresses, spread to the rest of the retina following a central-to-peripheral gradient. The results of this study suggest that S. aurata is an altricial teleost species that hatches with a morphologically undifferentiated retina. The most relevant processes involved in retinogenesis occur during the late prolarval stage (phase 3). PMID:26507100

  19. The Development of a Cat Model of Retinal Detachment and Re-attachment.

    PubMed

    Wassmer, Sarah; Leonard, Brian C; Coupland, Stuart G; Baker, Adam; Hamilton, John; Torlone, Renée; Zacks, David N; Tsilfidis, Catherine

    2016-01-01

    We present an optimized surgical technique for feline retinal detachment which allows for natural re-attachment, reduces retinal scarring and vitreal bands, and allows central placement of the detachment in close proximity to the optic nerve. This enables imaging via Optical Coherence Tomography (OCT) and multifocal electroretinography (mfERG) analysis. Ideal detachment conditions involve a lensectomy followed by a three-port pars plana vitrectomy. A 16-20 % retinal detachment is induced by injecting 8 % C3F8 gas into the subretinal space in the central retina with a 42G cannula. The retinal detachment resolves approximately 6 weeks post-surgery. Imaging is enhanced by using a 7.5 and 20 diopter lens for OCT and mfERG fundus imaging, respectively, to compensate for the removed lens. PMID:26427427

  20. Incidence and risk factors for Central Nervous System thrombosis in paediatric acute lymphoblastic leukaemia during intensive asparaginase treatment: a single-centre cohort study.

    PubMed

    Duarte, Ximo; Esteves, Susana; Neto, Ana M; Pereira, Filomena

    2016-07-01

    Central Nervous System (CNS) thrombosis is a complication of acute lymphoblastic leukaemia (ALL) treatment that is potentially associated with significant morbidity and neurological sequelae. Its presumably multifactorial aetiology is poorly characterized. We conducted a single-centre, retrospective cohort study on 346 ALL paediatric patients (1-16 years old) treated with asparaginase intensive Dana Farber Cancer Institute (DFCI) protocols from 1998 to 2011. The incidence, risk factors and outcome of CNS thrombosis were evaluated. CNS thrombosis occurred in 3·8% (13/346) of the patients (95% confidence interval 2·0-6·3%). Twelve events were diagnosed during intensification, all of which resolved within 2 weeks without neurological sequelae or significant impact in survival. Obesity (body mass index above 95th percentile) and asparaginase formulation were the only factors associated with CNS thrombosis, with an increase in the odds of event in obese patients [odds ratio (OR) = 3·37; P = 0·064] and a reduction in patients receiving Erwinia asparaginase (OR = 0·12; P = 0·018). No association could be demonstrated for age, gender, DFCI risk-group, ALL phenotype, steroid or doxorubicin use, central venous line use or CNS radiotherapy. CNS thrombosis is a rare but manageable adverse event without significant sequelae or detrimental effects in survival. Increased awareness is recommended in obese patients particularly during intensive asparaginase use. PMID:27018199

  1. Flexible retinal electrode array

    DOEpatents

    Okandan, Murat; Wessendorf, Kurt O.; Christenson, Todd R.

    2006-10-24

    An electrode array which has applications for neural stimulation and sensing. The electrode array can include a large number of electrodes each of which is flexibly attached to a common substrate using a plurality of springs to allow the electrodes to move independently. The electrode array can be formed from a combination of bulk and surface micromachining, with electrode tips that can include an electroplated metal (e.g. platinum, iridium, gold or titanium) or a metal oxide (e.g. iridium oxide) for biocompatibility. The electrode array can be used to form a part of a neural prosthesis, and is particularly well adapted for use in an implantable retinal prosthesis where the electrodes can be tailored to provide a uniform gentle contact pressure with optional sensing of this contact pressure at one or more of the electrodes.

  2. Building retinal connectomes.

    PubMed

    Marc, Robert E; Jones, Bryan W; Lauritzen, J Scott; Watt, Carl B; Anderson, James R

    2012-08-01

    Understanding vertebrate vision depends on knowing, in part, the complete network graph of at least one representative retina. Acquiring such graphs is the business of synaptic connectomics, emerging as a practical technology due to improvements in electron imaging platform control, management software for large-scale datasets, and availability of data storage. The optimal strategy for building complete connectomes uses transmission electron imaging with 2 nm or better resolution, molecular tags for cell identification, open-access data volumes for navigation, and annotation with open-source tools to build 3D cell libraries, complete network diagrams and connectivity databases. The first forays into retinal connectomics have shown that even nominally well-studied cells have much richer connection graphs than expected. PMID:22498714

  3. Nutrition and retinal degenerations.

    PubMed

    Berson, E L

    2000-01-01

    Considerable progress has been made in the understanding and management of degenerative diseases of the retina involving photoreceptors. Nutritional approaches to treatment have proved successful in the case of the common forms of retinitis pigmentosa (supplementation with vitamin A), Bassen-Kornzweig disease (supplementation with vitamins A, E, and K), gyrate atrophy (low-protein, low-arginine diet and/or supplementation with vitamin B6), and Refsum disease (low-phytol, low-phytanic acid diet). The night blindness associated with Sorsby fundus dystrophy can be reversed over the short term with vitamin A. A significant trend for decreased risk for advanced or exudative ARMD has been reported among those whose diets contain a higher content of carotenoids, such as spinach and collard greens. A randomized trial is in progress to determine whether beta-carotene, vitamin C, and vitamin E as well as trace minerals, particularly zinc, will modify the course of ARMD. The difficulties that patients with retinal degenerations face as a result of their diminishing vision, sometimes over decades, cannot be underestimated. Nutritional therapy has proved effective in modifying the course of a number of these conditions; the therapeutic benefit of nutritional modification in diseases that have a genetic basis is of particular interest. Further research is warranted to determine the mechanisms by which these treatments provide their benefit as well as to identify other conditions that may yield to nutritional intervention. Risk-factor analyses of well-defined populations followed over time with food-frequency questionnaires in conjunction with careful assessments of visual function may reveal other dietary constituents that can modify the course of degenerative diseases of the retina. PMID:11064860

  4. A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

    PubMed

    Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

    2004-06-01

    This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients. PMID:15255240

  5. Molecular genetics of retinitis pigmentosa.

    PubMed Central

    Farber, D. B.; Heckenlively, J. R.; Sparkes, R. S.; Bateman, J. B.

    1991-01-01

    Retinitis pigmentosa is a model for the study of genetic diseases. Its genetic heterogeneity is reflected in the different forms of inheritance (autosomal dominant, autosomal recessive, or X-linked) and, in a few families, in the presence of mutations in the visual pigment rhodopsin. Clinical and molecular genetic studies of these disorders are discussed. Animal models of retinal degeneration have been investigated for many years with the hope of gaining insight into the cause of photoreceptor cell death. Recently, the genes responsible for two of these animal disorders, the rds and rd mouse genes, have been isolated and characterized. The retinal degeneration of the rd mouse is presented in detail. The possible involvement of human analogues of these mouse genes in human retinal diseases is being investigated. Images PMID:1771877

  6. Increased Expression of Osteopontin in Retinal Degeneration Induced by Blue Light-Emitting Diode Exposure in Mice.

    PubMed

    Chang, Seung Wook; Kim, Hyung Il; Kim, Gyu Hyun; Park, Su Jin; Kim, In-Beom

    2016-01-01

    Osteopontin (OPN) is a multifunctional adhesive glycoprotein that is implicated in a variety of pro-inflammatory as well as neuroprotective and repair-promoting effects in the brain. As a first step towards understanding the role of OPN in retinal degeneration (RD), we examined changes in OPN expression in a mouse model of RD induced by exposure to a blue light-emitting diode (LED). RD was induced in BALB/c mice by exposure to a blue LED (460 nm) for 2 h. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In order to investigate changes in OPN in RD, western blotting and immunohistochemistry were performed. Anti-OPN labeling was compared to that of anti-glial fibrillary acidic protein (GFAP), which is a commonly used marker for retinal injury or stress including inflammation. OPN expression in RD retinas markedly increased at 24 h after exposure, was sustained through 72 h, and subsided at 120 h. Increased OPN expression was observed co-localized with microglial cells in the outer nuclear layer (ONL), outer plexiform layer (OPL), and subretinal space. Expression was restricted to the central retina in which photoreceptor cell death occurred. Interestingly, OPN expression in the ONL/OPL was closely associated with microglia, whereas most of the OPN plaques observed in the subretinal space were not. Immunogold electron microscopy demonstrated that OPN was distributed throughout the cytoplasm of microglia and in nearby fragments of degenerating photoreceptors. In addition, we found that OPN was induced more acutely and with greater region specificity than GFAP. These results indicate that OPN may be a more useful marker for retinal injury or stress, and furthermore act as a microglial pro-inflammatory mediator and a phagocytosis-inducing opsonin in the subretinal space. Taken together, our data suggest that OPN plays an important role in the pathogenesis of RD. PMID:27504084

  7. Increased Expression of Osteopontin in Retinal Degeneration Induced by Blue Light-Emitting Diode Exposure in Mice

    PubMed Central

    Chang, Seung Wook; Kim, Hyung Il; Kim, Gyu Hyun; Park, Su Jin; Kim, In-Beom

    2016-01-01

    Osteopontin (OPN) is a multifunctional adhesive glycoprotein that is implicated in a variety of pro-inflammatory as well as neuroprotective and repair-promoting effects in the brain. As a first step towards understanding the role of OPN in retinal degeneration (RD), we examined changes in OPN expression in a mouse model of RD induced by exposure to a blue light-emitting diode (LED). RD was induced in BALB/c mice by exposure to a blue LED (460 nm) for 2 h. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. In order to investigate changes in OPN in RD, western blotting and immunohistochemistry were performed. Anti-OPN labeling was compared to that of anti-glial fibrillary acidic protein (GFAP), which is a commonly used marker for retinal injury or stress including inflammation. OPN expression in RD retinas markedly increased at 24 h after exposure, was sustained through 72 h, and subsided at 120 h. Increased OPN expression was observed co-localized with microglial cells in the outer nuclear layer (ONL), outer plexiform layer (OPL), and subretinal space. Expression was restricted to the central retina in which photoreceptor cell death occurred. Interestingly, OPN expression in the ONL/OPL was closely associated with microglia, whereas most of the OPN plaques observed in the subretinal space were not. Immunogold electron microscopy demonstrated that OPN was distributed throughout the cytoplasm of microglia and in nearby fragments of degenerating photoreceptors. In addition, we found that OPN was induced more acutely and with greater region specificity than GFAP. These results indicate that OPN may be a more useful marker for retinal injury or stress, and furthermore act as a microglial pro-inflammatory mediator and a phagocytosis-inducing opsonin in the subretinal space. Taken together, our data suggest that OPN plays an important role in the pathogenesis of RD. PMID:27504084

  8. Acid-sensing ion channel 1a is involved in retinal ganglion cell death induced by hypoxia

    PubMed Central

    Tan, Jian; Xu, Yipin; Wang, Hao; Sheng, Minjie; Wang, Fang

    2011-01-01

    Purpose Loss of retinal ganglion cells (RGCs) during retinal ischemia is the potentially blinding mechanism that underlies several sight-threatening disorders. Fluctuations in extracellular pH are associated with such pathological conditions. It has been demonstrated that the retina is a functionally distinct region of central neurons that are known to contain acid-sensing ion channels (ASICs), which are depolarizing conductance channels directly activated by protons. This study was conducted to determine whether ASIC1a channels in RGCs are essential for ischemia-induced cell death. Methods Expression of ASIC1a channels was detected in primary cultures of rat RGCs and in retinal sections. The patch-clamp technique in the conventional whole-cell configuration was used to examine the currents evoked by acid in the cultured RGCs. Intracellular Ca2+ ([Ca2+]i) elevation was detected by Ca2+ imaging. Furthermore, hypoxia-induced cell death in RGC cultures was measured by methyl thiazolyl tetrazolium assay. Results RGCs expressed a high density of ASIC1a channels. The expression and function of ASIC1a channels were upregulated after hypoxia in cultured RGCs. Ratiometric Ca2+ imaging showed that RGCs responding to a drop in pH presented an increase in the concentration of (Ca2+)i. Acute blockade of ASIC1a channels with the specific inhibitor amiloride or psalmotoxin 1 reduced RGC death in vitro. Conclusions Based on these novel findings, we conclude that ASIC1a plays a role in RGC death induced by hypoxia. Therefore, neuroprotective strategies in glaucoma could include tools to improve the ability of these neurons to survive the cytotoxic consequences of ASIC1a activation. PMID:22194656

  9. A Rare Cause of Retinal Artery Occlusion in Severe Hypernatremic Dehydration in Newborns.

    PubMed

    Ozer, Pinar Altiaylik; Kabatas, Emrah Utku; Kurtul, Bengi Ece; Dilli, Dilek; Zenciroglu, Aysegul; Okumus, Nurullah

    2016-05-01

    Neonatal hypernatremia is an important electrolyte disorder that may have serious complications. It may be a rare and underdiagnosed cause of venous and arterial thrombosis, leading to severe brain damage by cerebral edema and intracranial hemorrhage. Here, the authors present a case of bilateral central retinal artery occlusion in a newborn with severe hypernatremic dehydration who is found to be normal in terms of other causes of retinal arterial thromboembolization. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:482-485.]. PMID:27183555

  10. Angiotensin inhibition in severe heart failure: acute central and limb hemodynamic effects of captopril with observations on sustained oral therapy.

    PubMed

    Faxon, D P; Halperin, J L; Creager, M A; Gavras, H; Schick, E C; Ryan, T J

    1981-05-01

    The systemic, pulmonary, and limb circulatory responses to the angiotensin-converting enzyme inhibitor, captopril, were determined in 10 patients with severe, chronic heart failure. Immediate effects include sustained reductions in arterial pressure and pulmonary capillary wedge pressure and improvement in cardiac output, as reported with other vasodilator drugs. Calf vascular resistance did not change despite substantial lowering of total systemic vascular resistance, indicating that arteriolar dilatation occurred on a selective basis. Transient reduction in mean right atrial pressure paralleled slight calf venodilatation, but effects upon the resistance vasculature predominated. Plasma renin activity and norepinephrine concentrations increased after therapy in the acute phase as plasma aldosterone levels consistently fell. During maintenance oral treatment over 7 to 15 months (median, 11.5 months), patients displayed symptomatic benefit, improved functional capacity, and greater exercise tolerance. No major adverse reactions developed. These findings suggest that angiotensin converting enzyme inhibition with captopril in congestive heart failure patients improved cardiocirculatory function through selective arteriolar dilatation. The reordering of regional blood flow which appears to result from release of angiotensin-mediated vasoconstriction, as well as the suppression of aldosterone, may underlie the prolonged benefit observed in these patients. This oral vasodilator appears to represent an effective adjunct for the treatment of advanced, chronic heart failure refractory to conventional measures. PMID:7013458

  11. Retinal oxygen extraction in humans

    NASA Astrophysics Data System (ADS)

    Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

    2015-10-01

    Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy.

  12. General pathophysiology in retinal degeneration.

    PubMed

    Wert, Katherine J; Lin, Jonathan H; Tsang, Stephen H

    2014-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  13. General Pathophysiology in Retinal Degeneration

    PubMed Central

    Wert, Katherine J.; Lin, Jonathan H.; Tsang, Stephen H.

    2015-01-01

    Retinal degeneration, including that seen in age-related macular degeneration and retinitis pigmentosa (RP), is the most common form of neural degenerative disease in the world. There is great genetic and allelic heterogeneity of the various retinal dystrophies. Classifications of these diseases can be ambiguous, as there are similar clinical presentations in retinal degenerations arising from different genetic mechanisms. As would be expected, alterations in the activity of the phototransduction cascade, such as changes affecting the renewal and shedding of the photoreceptor OS, visual transduction, and/ or retinol metabolism have a great impact on the health of the retina. Mutations within any of the molecules responsible for these visual processes cause several types of retinal and retinal pigment epithelium degenerative diseases. Apoptosis has been implicated in the rod cell loss seen in a mouse model of RP, but the precise mechanisms that connect the activation of these pathways to the loss of phosphodiesterase (PDE6β) function has yet to be defined. Additionally, the activation of apoptosis by CCAAT/-enhancer-binding protein homologous protein (CHOP), after activation of the unfolded protein response pathway, may be responsible for cell death, although the mechanism remains unknown. However, the mechanisms of cell death after loss of function of PDE6, which is a commonly studied mammalian model in research, may be generalizable to loss of function of different key proteins involved in the phototransduction cascade. PMID:24732759

  14. The mechanics of retinal detachment

    NASA Astrophysics Data System (ADS)

    Chou, Tom; Siegel, Michael

    2013-03-01

    We present a model of the mechanical and fluid forces associated with exudative retinal detachments where the retinal photoreceptor cells separate typically from the underlying retinal pigment epithelium (RPE). By computing the total fluid volume flow arising from transretinal, vascular, and retinal pigment epithelium (RPE) pump currents, we determine the conditions under which the subretinal fluid pressure exceeds the maximum yield stress holding the retina and RPE together, giving rise to an irreversible, extended retinal delamination. We also investigate localized, blister-like retinal detachments by balancing mechanical tension in the retina with both the retina-RPE adhesion energy and the hydraulic pressure jump across the retina. For detachments induced by traction forces, we find a critical radius beyond which the blister is unstable to growth. Growth of a detached blister can also be driven by inflamed tissue within which e.g., the hydraulic conductivities of the retina or choroid increase, the RPE pumps fail, or the adhesion properties change. We determine the parameter regimes in which the blister either becomes unstable to growth, remains stable and finite-sized, or shrinks, allowing possible healing. This work supported by the Army Research Office through grant 58386MA

  15. Cytomegalovirus retinitis mimicking intraocular lymphoma.

    PubMed

    Gooi, Patrick; Farmer, James; Hurley, Bernard; Brodbaker, Elliott

    2008-12-01

    We present a case of an unusual retinal infiltrate requiring retinal biopsy for definitive diagnosis. A 62-year-old man with treated lymphoma presented with decreased vision in the right eye associated with a white retinal lesion, which extended inferonasally from an edematous disc. Intraocular lymphoma was considered as a diagnosis; thus, the patient was managed with vitrectomy and retinal biopsy. Cytological analysis of the vitreous aspirate could not rule out a lymphoproliferative disorder. The microbial analysis was negative. Histology of the lesion showed extensive necrosis and large cells with prominent nucleoli. To rule out lymphoma, a battery of immunostains was performed and all were negative. However the limited amount of tissue was exhausted in the process. Subsequently, a hematoxylin and eosin (H/E) slide was destained, on which a CMV immunostain was performed. This revealed positivity in the nuclei and intranuclear inclusions within the large atypical cells. A diagnosis of CMV retinitis was made. Retinal biopsy may provide a definitive diagnosis and direct patient care toward intravenous gancyclovir in the case of CMV or toward radiation and chemotherapy for intraocular lymphoma. When faced with a limited amount of tissue, destaining regular H/E slides is a possible avenue to performing additional immunohistochemical studies. PMID:19668455

  16. Retinal oxygen extraction in humans.

    PubMed

    Werkmeister, René M; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A; Leitgeb, Rainer A; Schmetterer, Leopold

    2015-01-01

    Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy. PMID:26503332

  17. Retinal oxygen extraction in humans

    PubMed Central

    Werkmeister, René M.; Schmidl, Doreen; Aschinger, Gerold; Doblhoff-Dier, Veronika; Palkovits, Stefan; Wirth, Magdalena; Garhöfer, Gerhard; Linsenmeier, Robert A.; Leitgeb, Rainer A.; Schmetterer, Leopold

    2015-01-01

    Adequate function of the retina is dependent on proper oxygen supply. In humans, the inner retina is oxygenated via the retinal circulation. We present a method to calculate total retinal oxygen extraction based on measurement of total retinal blood flow using dual-beam bidirectional Doppler optical coherence tomography and measurement of oxygen saturation by spectrophotometry. These measurements were done on 8 healthy subjects while breathing ambient room air and 100% oxygen. Total retinal blood flow was 44.3 ± 9.0 μl/min during baseline and decreased to 18.7 ± 4.2 μl/min during 100% oxygen breathing (P < 0.001) resulting in a pronounced decrease in retinal oxygen extraction from 2.33 ± 0.51 μl(O2)/min to 0.88 ± 0.14 μl(O2)/min during breathing of 100% oxygen. The method presented in this paper may have significant potential to study oxygen metabolism in hypoxic retinal diseases such as diabetic retinopathy. PMID:26503332

  18. Expansion of first-in-class drug candidates that sequester toxic all-trans-retinal and prevent light-induced retinal degeneration.

    PubMed

    Zhang, Jianye; Dong, Zhiqian; Mundla, Sreenivasa Reddy; Hu, X Eric; Seibel, William; Papoian, Ruben; Palczewski, Krzysztof; Golczak, Marcin

    2015-01-01

    All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation. PMID:25538117

  19. Expansion of First-in-Class Drug Candidates That Sequester Toxic All-Trans-Retinal and Prevent Light-Induced Retinal Degeneration

    PubMed Central

    Zhang, Jianye; Dong, Zhiqian; Mundla, Sreenivasa Reddy; Hu, X. Eric; Seibel, William; Papoian, Ruben

    2015-01-01

    All-trans-retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all-trans-retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11-cis-retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all-trans-retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all-trans-retinyl ester into 11-cis-retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation. PMID:25538117

  20. Developing Cellular Therapies for Retinal Degenerative Diseases

    PubMed Central

    Bharti, Kapil; Rao, Mahendra; Hull, Sara Chandros; Stroncek, David; Brooks, Brian P.; Feigal, Ellen; van Meurs, Jan C.; Huang, Christene A.; Miller, Sheldon S.

    2014-01-01

    Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell–based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell–derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell–derived RPE, bone marrow– or umbilical cord–derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells–derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called “precompetitive space.” The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell–based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community. PMID:24573369

  1. Prevalence and Correlation of Infectious Agents in Hospitalized Children with Acute Respiratory Tract Infections in Central China

    PubMed Central

    Li, Fu; Wen, Zhou; Liu, Weiyong; Li, Tongya; Qin, Kai; Wu, Jianguo; Liu, Yingle

    2015-01-01

    Acute respiratory tract infections (ARTIs) are associated with significant morbidity and mortality worldwide, especially in children under the age of 5 years. Almost 2 million children die from ARTIs each year, and most of them are from developing countries. The prevalence and correlation of pathogens in ARTIs are poorly understood, but are critical for improving case prevention, treatment, and management. In this study, we investigated the prevalence and correlation of infectious agents in children with ARTIs. A total of 39,756 children with one or more symptoms, including fever, cough, sore throat, tonsillitis, pharyngitis, herpangina, pneumonia, and bronchiolitis, were enrolled in the study. All patients were hospitalized in Wuhan Children’s Hospital between October 1, 2010 and September 30, 2012, and were evaluated for infectious agents. Pathogens, including Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenoviruses, respiratory syncytial virus, parainfluenza virus, Legionella pneumophila, Chlamydophila pneumoniae, and Coxiella burnetii, were screened simultaneously in patient blood samples using anti-pathogen IgM tests. Regression analysis was used to reveal correlations among the pathogens. Our results showed that one or more pathogens were identified in 10,206 patients, and that Mycoplasma pneumoniae, adenoviruses, and influenza B virus were the leading infectious agents. Mixed-infections of pathogens were detected in 2,391 cases, with Mycoplasma pneumoniae as the most frequent pathogen. The most common agents in the co-infections were Mycoplasma pneumoniae and influenza B virus. Regression analysis revealed a linear correlation between the proportion of mixed infections and the incidence of multi-pathogen infections. The prevalence of infectious agents in children with ARTIs was determined. Equations were established to estimate multiple infections by single-pathogen detection. This revealed a linear correlation for pathogens in children

  2. Prevalence and correlation of infectious agents in hospitalized children with acute respiratory tract infections in Central China.

    PubMed

    Liu, Jia; Ai, Hongwu; Xiong, Ying; Li, Fu; Wen, Zhou; Liu, Weiyong; Li, Tongya; Qin, Kai; Wu, Jianguo; Liu, Yingle

    2015-01-01

    Acute respiratory tract infections (ARTIs) are associated with significant morbidity and mortality worldwide, especially in children under the age of 5 years. Almost 2 million children die from ARTIs each year, and most of them are from developing countries. The prevalence and correlation of pathogens in ARTIs are poorly understood, but are critical for improving case prevention, treatment, and management. In this study, we investigated the prevalence and correlation of infectious agents in children with ARTIs. A total of 39,756 children with one or more symptoms, including fever, cough, sore throat, tonsillitis, pharyngitis, herpangina, pneumonia, and bronchiolitis, were enrolled in the study. All patients were hospitalized in Wuhan Children's Hospital between October 1, 2010 and September 30, 2012, and were evaluated for infectious agents. Pathogens, including Mycoplasma pneumoniae, influenza A virus, influenza B virus, adenoviruses, respiratory syncytial virus, parainfluenza virus, Legionella pneumophila, Chlamydophila pneumoniae, and Coxiella burnetii, were screened simultaneously in patient blood samples using anti-pathogen IgM tests. Regression analysis was used to reveal correlations among the pathogens. Our results showed that one or more pathogens were identified in 10,206 patients, and that Mycoplasma pneumoniae, adenoviruses, and influenza B virus were the leading infectious agents. Mixed-infections of pathogens were detected in 2,391 cases, with Mycoplasma pneumoniae as the most frequent pathogen. The most common agents in the co-infections were Mycoplasma pneumoniae and influenza B virus. Regression analysis revealed a linear correlation between the proportion of mixed infections and the incidence of multi-pathogen infections. The prevalence of infectious agents in children with ARTIs was determined. Equations were established to estimate multiple infections by single-pathogen detection. This revealed a linear correlation for pathogens in children with

  3. Effects of acute tryptophan depletion on central processing of CT-targeted and discriminatory touch in humans.

    PubMed

    Trotter, Paula Diane; McGlone, Francis; McKie, Shane; McFarquhar, Martyn; Elliott, Rebecca; Walker, Susannah Claire; Deakin, John Francis William

    2016-08-01

    C-tactile afferents (CTs) are slowly conducting nerve fibres, present only in hairy skin. They are optimally activated by slow, gentle stroking touch, such as those experienced during a caress. CT stimulation activates affective processing brain regions, alluding to their role in affective touch perception. We tested a theory that CT-activating touch engages the pro-social functions of serotonin, by determining whether reducing serotonin, through acute tryptophan depletion, diminishes subjective pleasantness and affective brain responses to gentle touch. A tryptophan depleting amino acid drink was administered to 16 healthy females, with a further 14 receiving a control drink. After 4 h, participants underwent an fMRI scan, during which time CT-innervated forearm skin and CT non-innervated finger skin was stroked with three brushes of differing texture, at CT-optimal force and velocity. Pleasantness ratings were obtained post scanning. The control group showed a greater response in ipsilateral orbitofrontal cortex to CT-activating forearm touch compared to touch to the finger where CTs are absent. This differential response was not present in the tryptophan depleted group. This interaction effect was significant. In addition, control participants showed a differential primary somatosensory cortex response to brush texture applied to the finger, a purely discriminatory touch response, which was not observed in the tryptophan depleted group. This interaction effect was also significant. Pleasantness ratings were similar across treatment groups. These results implicate serotonin in the differentiation between CT-activating and purely discriminatory touch responses. Such effects could contribute to some of the social abnormalities seen in psychiatric disorders associated with abnormal serotonin function. PMID:27307373

  4. Long-term control of CMV retinitis in a patient with idiopathic CD4+ T lymphocytopenia.

    PubMed

    Yashiro, Shigeko; Fujino, Yujiro; Tachikawa, Natsuo; Inamochi, Kazuya; Oka, Shinichi

    2013-04-01

    Cytomegalovirus (CMV) retinitis with idiopathic CD4(+) T lymphocytopenia (ICL) is rare and difficult to control. We report a first case for long-term control of CMV retinitis with ICL using interleukin-2 (IL-2) therapy and succeeded in discontinuation of anti-CMV therapy. A 49-year-old Japanese woman was diagnosed with ICL based on low CD4(+) count (72/μl), negative for HIV-1 and -2 antibodies, and absence of any defined immunodeficiency diseases or immunosuppressive therapy. PCR test of the aqueous humor in the right eye was suggestive of CMV retinitis. She was treated with systemic ganciclovir, but after several relapses of CMV retinitis, rhegmatogenous retinal detachment appeared in the right eye and she became blind in that eye. Three years later, she developed CMV retinitis in the left eye. Although she received systemic and focal anti-CMV treatments, the retinitis showed no improvement. Finally, retinal detachment occurred, and she underwent vitrectomy. IL-2 was injected to increase CD4(+) counts. Because of hyperpyrexia, blepharedema, central scotoma, and color anomaly, we changed to low-dose IL-2 therapy with no side effects. Finally, we succeeded in increasing the CD4(+) count to more than 200/μl after discontinuation of low-dose IL-2 therapy. CMV retinitis never recurred after discontinuation of anti-CMV therapy, with good visual acuity of 20/20 in the left eye. She developed blindness of the first affected right eye, whereas the visual acuity of the left eye remains excellent more than 12 years after the onset of CMV retinitis through the combined use of anti-CMV therapy, IL-2 therapy, and vitrectomy. PMID:22935818

  5. Neuroprotective effect of minocycline in a rat model of branch retinal vein occlusion.

    PubMed

    Sun, Chuan; Li, Xiao-Xin; He, Xiang-Jun; Zhang, Qi; Tao, Yong

    2013-08-01

    Branch retinal vein occlusion (BRVO) is the second most frequent retinal vascular disorder. Currently the first-line therapies for BRVO include anti-VEGF and dexamethasone implant treatment, however, with direct or indirect damage on retinal neurons, it has limited effect in improving patients visual acuity. Therefore, novel treatments with neuroprotective effect for BRVO retina were expected. Minocycline is a semisynthetic, broad spectrum tetracycline antibiotic with high penetration through the blood brain barrier. The neuroprotective effects of minocycline have been shown in various central nervous system (CNS) disease. Since both CNS and retina were composed of neurons and glials, it is reasonable to expect a neuroprotective effect by minocycline for BRVO retina. Therefore, the aim of the present study was to study whether minocycline has neuroprotective effect in branch retinal vein occlusion (BRVO) and the possible underlying molecular basis. We created BRVO in rats using laser photocoagulation. The animals were then randomly divided into 4 groups to evaluate the effect of minocycline: group A: minocycline 45 mg/kg intraperitoneal injection (i.p.), group B: minocycline 90 mg/kg i.p., group C: normal saline i.p., group D: sham injection. Fundus photography and fluorescein angiography (FA) were conducted. The changes in thickness of retinal layers were measured with optical coherence tomography (OCT) in vivo. We found that retinal edema occurred predominantly in the inner retinal layers. Intraperitoneal administration of minocycline significantly ameliorated retinal edema in the early stage of BRVO. We performed Full field Electroretinography (ffERG) to evaluate retinal function and found that the reduction of b wave amplitude decreased in the combined maximal response. The expressional levels of apoptosis related genes (Bax, Bcl-2) and inflammation related genes (IL-1 β, TNF α, MCP-1 and CCR2) were measured by real-time PCR, the results showed that

  6. Acute up-regulation of the rat brain somatostatin receptor-effector system by leptin is related to activation of insulin signaling and may counteract central leptin actions.

    PubMed

    Perianes-Cachero, A; Burgos-Ramos, E; Puebla-Jiménez, L; Canelles, S; Frago, L M; Hervás-Aguilar, A; de Frutos, S; Toledo-Lobo, M V; Mela, V; Viveros, M P; Argente, J; Chowen, J A; Arilla-Ferreiro, E; Barrios, V

    2013-11-12

    Leptin and somatostatin (SRIF) have opposite effects on food seeking and ingestive behaviors, functions partially regulated by the frontoparietal cortex and hippocampus. Although it is known that the acute suppression of food intake mediated by leptin decreases with time, the counter-regulatory mechanisms remain unclear. Our aims were to analyze the effect of acute central leptin infusion on the SRIF receptor-effector system in these areas and the implication of related intracellular signaling mechanisms in this response. We studied 20 adult male Wister rats including controls and those treated intracerebroventricularly with a single dose of 5 μg of leptin and sacrificed 1 or 6h later. Density of SRIF receptors was unchanged at 1h, whereas leptin increased the density of SRIF receptors at 6h, which was correlated with an elevated capacity of SRIF to inhibit forskolin-stimulated adenylyl cyclase activity in both areas. The functional capacity of SRIF receptors was unaltered as cell membrane levels of αi1 and αi2 subunits of G inhibitory proteins were unaffected in both brain areas. The increased density of SRIF receptors was due to enhanced SRIF receptor subtype 2 (sst2) protein levels that correlated with higher mRNA levels for this receptor. These changes in sst2 mRNA levels were concomitant with increased activation of the insulin signaling, c-Jun and cyclic AMP response element-binding protein (CREB); however, activation of signal transducer and activator of transcription 3 was reduced in the cortex and unchanged in the hippocampus and suppressor of cytokine signaling 3 remained unchanged in these areas. In addition, the leptin antagonist L39A/D40A/F41A blocked the leptin-induced changes in SRIF receptors, leptin signaling and CREB activation. In conclusion, increased activation of insulin signaling after leptin infusion is related to acute up-regulation of the SRIF receptor-effector system that may antagonize short-term leptin actions in the rat brain. PMID

  7. Disruption of neuroendocrine stress responses to acute ferret odor by medial, but not central amygdala lesions in rats

    PubMed Central

    Masini, Cher V.; Sasse, Sarah K.; Garcia, Robert J.; Nyhuis, Tara J.; Day, Heidi E.W.; Campeau, Serge

    2009-01-01

    Investigations of the neural pathways associated with responses to predators have implicated the medial amygdala (MeA) as an important region involved in defensive behaviors. To our knowledge, however, the involvement of the MeA in neuroendocrine responses to predator odor exposure has not been investigated. Therefore, the present study examined the effects of MeA disruption in rats exposed to ferret or control odor on hypothalamo-pituitary-adrenocortical (HPA) axis activation. Bilateral lesions of the MeA were made in Sprague- Dawley rats with the neurotoxin ibotenic acid (10 µg/µl; 0.3 µl /side). As a control for regional specificity, additional groups of rats were given lesions in the central amygdala (CeA). One week after recovery, the rats were exposed to ferret or strawberry control towels in small cages to examine HPA axis responses as determined by plasma corticosterone and adrenocorticotropin hormone (ACTH) levels. Rats with complete bilateral MeA but not CeA lesions displayed significantly less corticosterone and ACTH release compared to sham-operated control rats only in the ferret odor conditions. These results suggest that the MeA is an important structure involved in the HPA axis responses to predator odors, in support of previous studies investigating behavioral responses under similar conditions. PMID:19615352

  8. Optoelectronic retinal prosthesis: system design and performance

    NASA Astrophysics Data System (ADS)

    Loudin, J. D.; Simanovskii, D. M.; Vijayraghavan, K.; Sramek, C. K.; Butterwick, A. F.; Huie, P.; McLean, G. Y.; Palanker, D. V.

    2007-03-01

    The design of high-resolution retinal prostheses presents many unique engineering and biological challenges. Ever smaller electrodes must inject enough charge to stimulate nerve cells, within electrochemically safe voltage limits. Stimulation sites should be placed within an electrode diameter from the target cells to prevent 'blurring' and minimize current. Signals must be delivered wirelessly from an external source to a large number of electrodes, and visual information should, ideally, maintain its natural link to eye movements. Finally, a good system must have a wide range of stimulation currents, external control of image processing and the option of either anodic-first or cathodic-first pulses. This paper discusses these challenges and presents solutions to them for a system based on a photodiode array implant. Video frames are processed and imaged onto the retinal implant by a head-mounted near-to-eye projection system operating at near-infrared wavelengths. Photodiodes convert light into pulsed electric current, with charge injection maximized by applying a common biphasic bias waveform. The resulting prosthesis will provide stimulation with a frame rate of up to 50 Hz in a central 10° visual field, with a full 30° field accessible via eye movements. Pixel sizes are scalable from 100 to 25 µm, corresponding to 640-10 000 pixels on an implant 3 mm in diameter.

  9. Eye Morphology and Retinal Topography in Hummingbirds (Trochilidae: Aves).

    PubMed

    Lisney, Thomas J; Wylie, Douglas R; Kolominsky, Jeffrey; Iwaniuk, Andrew N

    2015-01-01

    Hummingbirds are a group of small, highly specialized birds that display a range of adaptations to their nectarivorous lifestyle. Vision plays a key role in hummingbird feeding and hovering behaviours, yet very little is known about the visual systems of these birds. In this study, we measured eye morphology in 5 hummingbird species. For 2 of these species, we used stereology and retinal whole mounts to study the topographic distribution of neurons in the ganglion cell layer. Eye morphology (expressed as the ratio of corneal diameter to eye transverse diameter) was similar among all 5 species and was within the range previously documented for diurnal birds. Retinal topography was similar in Amazilia tzacatl and Calypte anna. Both species had 2 specialized retinal regions of high neuron density: a central region located slightly dorso-nasal to the superior pole of the pecten, where densities reached ∼ 45,000 cells · mm(-2), and a temporal area with lower densities (38,000-39,000 cells · mm(-2)). A weak visual streak bridged the two high-density areas. A retina from Phaethornis superciliosus also had a central high-density area with a similar peak neuron density. Estimates of spatial resolving power for all 3 species were similar, at approximately 5-6 cycles · degree(-1). Retinal cross sections confirmed that the central high-density region in C. anna contains a fovea, but not the temporal area. We found no evidence of a second, less well-developed fovea located close to the temporal retina margin. The central and temporal areas of high neuron density allow for increased spatial resolution in the lateral and frontal visual fields, respectively. Increased resolution in the frontal field in particular may be important for mediating feeding behaviors such as aerial docking with flowers and catching small insects. PMID:26587582

  10. Chemical Exacerbation of Light-induced Retinal Degeneration in F344/N Rats in National Toxicology Program Rodent Bioassays.

    PubMed

    Yamashita, Haruhiro; Hoenerhoff, Mark J; Peddada, Shyamal D; Sills, Robert C; Pandiri, Arun R

    2016-08-01

    Retinal degeneration due to chronic ambient light exposure is a common spontaneous age-related finding in albino rats, but it can also be related to exposures associated with environmental chemicals and drugs. Typically, light-induced retinal degeneration has a central/hemispherical localization whereas chemical-induced retinal degeneration has a diffuse localization. This study was conducted to identify and characterize treatment-related retinal degeneration in National Toxicology Program rodent bioassays. A total of 3 chronic bioassays in F344/N rats (but not in B6C3F1/N mice) were identified that had treatment-related increases in retinal degeneration (kava kava extract, acrylamide, and leucomalachite green). A retrospective light microscopic evaluation of the retinas from rats in these 3 studies showed a dose-related increase in the frequencies of retinal degeneration, beginning with the loss of photoreceptor cells, followed by the inner nuclear layer cells. These dose-related increased frequencies of degenerative retinal lesions localized within the central/hemispherical region are suggestive of exacerbation of light-induced retinal degeneration. PMID:27230502

  11. Retinal AO OCT

    NASA Astrophysics Data System (ADS)

    Zawadzki, Robert J.; Miller, Donald T.

    The last two decades have witnessed extraordinary advances in optical technology to image noninvasively and at high resolution the posterior segment of the eye. Two of the most impactful technological advancements over this period have arguably been optical coherence tomography (OCT) and adaptive optics (AO). The strengths of these technologies complement each other and when combined have been shown to provide unprecedented, micron-scale resolution (<3 μm) in all three dimensions and sensitivity to image the cellular retina in the living eye. This powerful extension of OCT, that is AO-OCT, is the focus of this chapter. It presents key aspects of designing and implementing AO-OCT systems. Particular attention is devoted to the relevant optical properties of the eye that ultimately define these systems, AO componentry and operation tailored for ophthalmic use, and of course use of the latest technologies and methods in OCT for ocular imaging. It surveys the wide range of AO-OCT designs that have been developed for retinal imaging, with AO integrated into every major OCT design configuration. Finally, it reviews the scientific and clinical studies reported to date that show the exciting potential of AO-OCT to image the microscopic retina and fundus in ways not previously possible with other noninvasive methods and a look to future developments in this rapidly growing field.

  12. Temperature controlled retinal photocoagulation

    NASA Astrophysics Data System (ADS)

    Schlott, Kerstin; Koinzer, Stefan; Baade, Alexander; Birngruber, Reginald; Roider, Johann; Brinkmann, Ralf

    2013-06-01

    Retinal photocoagulation lacks objective dosage in clinical use, thus the commonly applied lesions are too deep and strong, associated with pain reception and the risk of visual field defects and induction of choroidal neovascularisations. Optoacoustics allows real-time non-invasive temperature measurement in the fundus during photocoagulation by applying short probe laser pulses additionally to the treatment radiation, which excite the emission of ultrasonic waves. Due to the temperature dependence of the Grüneisen parameter, the amplitudes of the ultrasonic waves can be used to derive the temperature of the absorbing tissue. By measuring the temperatures in real-time and automatically controlling the irradiation by feedback to the treatment laser, the strength of the lesions can be defined. Different characteristic functions for the time and temperature dependent lesion sizes were used as rating curves for the treatment laser, stopping the irradiation automatically after a desired lesion size is achieved. The automatically produced lesion sizes are widely independent of the adjusted treatment laser power and individual absorption. This study was performed on anaesthetized rabbits and is a step towards a clinical trial with automatically controlled photocoagulation.

  13. Central role of intracellular calcium stores in acute flow- and agonist-evoked endothelial nitric oxide release.

    PubMed

    Hutcheson, I R; Griffith, T M

    1997-09-01

    isolated aortic ring preparations were markedly attenuated by pretreatment with CPA and TSG, but were unaffected by ryanodine. Ryanodine and CPA caused only a small attenuation of endothelium-independent relaxations to sodium nitroprusside (0.001-10 microM), whereas TSG had no effect. 7. We conclude that release of Ca2+ from CPA- and TSG-sensitive endothelial stores is necessary for NO release evoked by acute flow changes and agonists in rabbit abdominal aorta. Ca(2+)-induced Ca2+ release via the ryanodine-sensitive release channel plays no direct role in these responses. Free radical interactions may complicate the interpretation of findings in cascade bioassay compared with isolated ring preparations. PMID:9298537

  14. Study of retinal vessel oxygen saturation in ischemic and non-ischemic branch retinal vein occlusion

    PubMed Central

    Lin, Lei-Lei; Dong, Yan-Min; Zong, Yao; Zheng, Qi-Shan; Fu, Yue; Yuan, Yong-Guang; Huang, Xia; Qian, Garrett; Gao, Qian-Ying

    2016-01-01

    AIM To explore how oxygen saturation in retinal blood vessels is altered in ischemic and non-ischemic branch retinal vein occlusion (BRVO). METHODS Fifty BRVO eyes were divided into ischemic (n=26) and non-ischemic (n=24) groups, based on fundus fluorescein angiography. Healthy individuals (n=52 and n=48, respectively) were also recruited as controls for the two groups. The mean oxygen saturations of the occluded vessels and central vessels were measured by oximetry in the BRVO and control groups. RESULTS In the ischemic BRVO group, the occluded arterioles oxygen saturation (SaO2-A, 106.0%±14.3%), instead of the occluded venule oxygen saturation (SaO2-V, 60.8%±9.4%), showed increases when compared with those in the same quadrant vessels (SaO2-A, 86.1%±16.5%) in the contralateral eyes (P<0.05). The oxygen saturations of the central vessels showed similar trends with those of the occluded vessels. In the non-ischemic BRVO group, the occluded and central SaO2-V and SaO2-A showed no significant changes. In both the ischemic and non-ischemic BRVOs, the central SaO2-A was significantly increased when compared to healthy individuals. CONCLUSION Obvious changes in the occluded and central SaO2-A were found in the ischemic BRVO group, indicating that disorders of oxygen metabolism in the arterioles may participate in the pathogenesis of ischemic BRVO. PMID:26949618

  15. Randomized trial of radiation-free central nervous system prophylaxis comparing intrathecal triple therapy with liposomal cytarabine in acute lymphoblastic leukemia

    PubMed Central

    Bassan, Renato; Masciulli, Arianna; Intermesoli, Tamara; Audisio, Ernesta; Rossi, Giuseppe; Pogliani, Enrico Maria; Cassibba, Vincenzo; Mattei, Daniele; Romani, Claudio; Cortelezzi, Agostino; Corti, Consuelo; Scattolin, Anna Maria; Spinelli, Orietta; Tosi, Manuela; Parolini, Margherita; Marmont, Filippo; Borlenghi, Erika; Fumagalli, Monica; Cortelazzo, Sergio; Gallamini, Andrea; Marfisi, Rosa Maria; Oldani, Elena; Rambaldi, Alessandro

    2015-01-01

    Developing optimal radiation-free central nervous system prophylaxis is a desirable goal in acute lymphoblastic leukemia, to avoid the long-term toxicity associated with cranial irradiation. In a randomized, phase II trial enrolling 145 adult patients, we compared intrathecal liposomal cytarabine (50 mg: 6/8 injections in B-/T-cell subsets, respectively) with intrathecal triple therapy (methotrexate/cytarabine/prednisone: 12 injections). Systemic therapy included methotrexate plus cytarabine or L-asparaginase courses, with methotrexate augmented to 2.5 and 5 g/m2 in Philadelphia-negative B- and T-cell disease, respectively. The primary study objective was the comparative assessment of the risk/benefit ratio, combining the analysis of feasibility, toxicity and efficacy. In the liposomal cytarabine arm 17/71 patients (24%) developed grade 3–4 neurotoxicity compared to 2/74 (3%) in the triple therapy arm (P=0.0002), the median number of episodes of neurotoxicity of any grade was one per patient compared to zero, respectively (P=0.0001), and even though no permanent disabilities or deaths were registered, four patients (6%) discontinued intrathecal prophylaxis on account of these toxic side effects (P=0.06). Neurotoxicity worsened with liposomal cytarabine every 14 days (T-cell disease), and was improved by the adjunct of intrathecal dexamethasone. Two patients in the liposomal cytarabine arm suffered from a meningeal relapse (none with T-cell disease, only one after high-dose chemotherapy) compared to four in the triple therapy arm (1 with T-cell disease). While intrathecal liposomal cytarabine could contribute to improved, radiation-free central nervous system prophylaxis, the toxicity reported in this trial does not support its use at 50 mg and prompts the investigation of a lower dosage. (clinicaltrials.gov identifier: NCT-00795756). PMID:25749825

  16. The substantial hospitalization burden of influenza in central China: surveillance for severe, acute respiratory infection, and influenza viruses, 2010–2012

    PubMed Central

    Yu, Hongjie; Huang, Jigui; Huai, Yang; Guan, Xuhua; Klena, John; Liu, Shali; Peng, Youxing; Yang, Hui; Luo, Jun; Zheng, Jiandong; Chen, Maoyi; Peng, Zhibin; Xiang, Nijuan; Huo, Xixiang; Xiao, Lin; Jiang, Hui; Chen, Hui; Zhang, Yuzhi; Xing, Xuesen; Xu, Zhen; Feng, Zijian; Zhan, Faxian; Yang, Weizhong; Uyeki, Timothy M; Wang, Yu; Varma, Jay K

    2014-01-01

    Background Published data on influenza in severe acute respiratory infection (SARI) patients are limited. We conducted SARI surveillance in central China and estimated hospitalization rates of SARI attributable to influenza by viral type/subtype. Methods Surveillance was conducted at four hospitals in Jingzhou, China from 2010 to 2012. We enrolled hospitalized patients who had temperature ≥37·3°C and at least one of: cough, sore throat, tachypnea, difficulty breathing, abnormal breath sounds on auscultation, sputum production, hemoptysis, chest pain, or chest radiograph consistent with pneumonia. A nasopharyngeal swab was collected from each case-patient within 24 hours of admission for influenza testing by real-time reverse transcription PCR. Results Of 17 172 SARI patients enrolled, 90% were aged <15 years. The median duration of hospitalization was 5 days. Of 16 208 (94%) SARI cases tested, 2057 (13%) had confirmed influenza, including 1427 (69%) aged <5 years. Multiple peaks of influenza occurred during summer, winter, and spring months. Influenza was associated with an estimated 115 and 142 SARI hospitalizations per 100 000 during 2010–2011 and 2011–2012 [including A(H3N2): 55 and 44 SARI hospitalizations per 100 000; pandemic A(H1N1): 33 SARI hospitalizations per 100 000 during 2010–2011; influenza B: 26 and 98 hospitalizations per 100 000], with the highest rate among children aged 6–11 months (3603 and 3805 hospitalizations per 100 000 during 2010–2011 and 2011–2012, respectively). Conclusions In central China, influenza A and B caused a substantial number of hospitalizations during multiple periods each year. Our findings strongly suggest that young children should be the highest priority group for annual influenza vaccination in China. PMID:24209711

  17. Reduced Genetic Diversity in Lymphoid and Central Nervous System Tissues and Selection-Induced Tissue-Specific Compartmentalization of Neuropathogenic SIVsmmFGb during Acute Infection

    PubMed Central

    Reeve, Aaron B.; Patel, Kalpana; Pearce, Nicholas C.; Augustus, Katherine V.; Domingues, Heber G.; O'Neil, Shawn P.

    2009-01-01

    Abstract The simian lentivirus strain SIVsmmFGb is a viral swarm population inducing neuropathology in over 90% of infected pigtailed macaques and serves as a reliable model for HIV neuropathogenesis. However, little is understood about the genetic diversity of this virus, how said diversity influences the initial seeding of the central nervous system and lymph nodes, or whether the virus forms distinct genetic compartments between tissues during acute infection. In this study, we establish that our SIVsmmFGb stock virus contains four genetically distinct envelope V1 region groups, three distinct integrase groups, and two Nef groups. We demonstrate that initial central nervous system and lymph node seeding reduces envelope V1 and integrase genetic diversity but has a variable effect on Nef diversity. SIVsmmFGb envelope V1 region genes from the basal ganglia, cerebellum, and hippocampus form distinct genetic compartments from each other, the midfrontal cortex, and the lymph nodes. Basal ganglia, cerebellum, hippocampus, and midfrontal cortex-derived nef genes all form distinct genetic compartments from each other, as well as from the lymph nodes. We also find basal ganglia, hippocampus, and midfrontal cortex-derived integrase sequences forming distinct compartments from both of the lymph nodes and that the hippocampus and midfrontal cortex form separate compartments from the cerebellum, while the axillary and mesenteric lymph nodes compartmentalize separately from each other. Compartmentalization of the envelope V1 genes resulted from positive selection, and compartmentalization of the nef and integrase genes from negative selection. These results indicate restrictions on virus genetic diversity during initial tissue seeding in neuropathogenic SIV infection. PMID:19500015

  18. Photon Echoes from Retinal Proteins

    NASA Astrophysics Data System (ADS)

    Johnson, Philip James Maddigan

    This thesis focuses on the ultrafast isomerization reaction of retinal in both rhodopsin and bacteriorhodopsin, examples of sensory and energy transduction proteins that exploit the same photoactive chromophore for two very different functions. In bacteriorhodopsin, retinal isomerizes from an all-trans to 13-cis conformation as the primary event in light- driven proton pumping. In the visual pigment rhodopsin, the retinal chromophore isomerizes from an 11-cis to all-trans geometry as the primary step leading to our sense of vision. This diversity of function for nominally identical systems raises the question as to just how optimized are these proteins to arrive at such drastically different functions? Previous work has employed transient absorption spectroscopy to probe retinal protein photochemistry, but many of the relevant electronic and nuclear dynamics of isomerization are masked by inhomogeneous broadening effects and strong spectral overlap between reactant and photoproduct states. This work exploits the unique properties of two-dimensional photon echo spectroscopy to deconvolve inhomogeneous broadening and spectral overlap effects and fully reveal the dynamics that direct retinal isomerization in proteins. In bacteriorhodopsin, vibrational coupling to the reaction coordinate results in a surface crossing event prior to the conventional conical intersection associated with isomerization to the J intermediate. In rhodopsin, however, a similarly early vibrationally-mediated barrier crossing event is observed, resulting in spectral signals consistent with the known photoproduct state appearing an order of magnitude faster than determined from conventional transient absorption measurements. The competing overlapping spectral signals that obscured the initial dynamics when probed with transient absorption spectroscopy are now clearly resolved with two-dimensional photon echo spectroscopy. These experiments illustrate the critical role of the protein in directing

  19. Visual sensorial impairments in neurodevelopmental disorders: evidence for a retinal phenotype in Fragile X Syndrome.

    PubMed

    Rossignol, Rafaëlle; Ranchon-Cole, Isabelle; Pâris, Arnaud; Herzine, Ameziane; Perche, Astrid; Laurenceau, David; Bertrand, Pauline; Cercy, Christine; Pichon, Jacques; Mortaud, Stéphane; Briault, Sylvain; Menuet, Arnaud; Perche, Olivier

    2014-01-01

    Visual sensory impairments are common in Mental Deficiency (MD) and Autism Spectrum Disorder (ASD). These defects are linked to cerebral dysfunction in the visual cortical area characterized by the deregulation of axon growth/guidance and dendrite spine immaturity of neurons. However, visual perception had not been addressed, although the retina is part of the central nervous system with a common embryonic origin. Therefore, we investigated retinal perception, the first event of vision, in a murine model of MD with autistic features. We document that retinal function is altered in Fmr1 KO mice, a model of human Fragile X Syndrome. Indeed, In Fmr1 KO mice had a lower retinal function characterized by a decreased photoreceptors neuron response, due to a 40% decrease in Rhodopsin content and to Rod Outer Segment destabilization. In addition, we observed an alteration of the visual signal transmission between photoreceptors and the inner retina which could be attributed to deregulations of pre- and post- synaptic proteins resulting in retinal neurons synaptic destabilization and to retinal neurons immaturity. Thus, for the first time, we demonstrated that retinal perception is altered in a murine model of MD with autistic features and that there are strong similarities between cerebral and retinal cellular and molecular defects. Our results suggest that both visual perception and integration must be taken into account in assessing visual sensory impairments in MD and ASD. PMID:25153086

  20. Summarising the retinal vascular calibres in healthy, diabetic and diabetic retinopathy eyes.

    PubMed

    Leontidis, Georgios; Al-Diri, Bashir; Hunter, Andrew

    2016-05-01

    Retinal vessel calibre has been found to be an important biomarker of several retinal diseases, including diabetic retinopathy (DR). Quantifying the retinal vessel calibres is an important step for estimating the central retinal artery and vein equivalents. In this study, an alternative method to the already established branching coefficient (BC) is proposed for summarising the vessel calibres in retinal junctions. This new method combines the mean diameter ratio with an alternative to Murray׳s cube law exponent, derived by the fractal dimension,experimentally, and the branch exponent of cerebral vessels, as has been suggested in previous studies with blood flow modelling. For the above calculations, retinal images from healthy, diabetic and DR subjects were used. In addition, the above method was compared with the BC and was also applied to the evaluation of arteriovenous ratio as a biomarker of progression from diabetes to DR in four consecutive years, i.e. three/two/one years before the onset of DR and the first year of DR. Moreover, the retinal arteries and veins around the optic nerve head were also evaluated. The new approach quantifies the vessels more accurately. The decrease in terms of the mean absolute percentage error was between 0.24% and 0.49%, extending at the same time the quantification beyond healthy subjects. PMID:27017067

  1. Automated retinal robotic laser system.

    PubMed

    Barrett, S F; Wright, C H; Jerath, M R; Lewis, R S; Dillard, B C; Rylander, H G; Welch, A J

    1995-01-01

    Researchers at the University of Texas and the USAF Academy have worked toward the development of a retinal robotic laser system. The overall goal of this ongoing project is to precisely place and control the depth of laser lesions for the treatment of various retinal diseases such as diabetic retinopathy and retinal tears. Separate low speed prototype subsystems have been developed to control lesion depth using lesion reflectance feedback parameters and lesion placement using retinal vessels as tracking landmarks. Both subsystems have been successfully demonstrated in vivo on pigmented rabbits using an argon continuous wave laser. Recent efforts have concentrated on combining the two subsystems into a single prototype capable of simultaneously controlling both lesion depth and placement. We have designated this combined system CALOSOS for Computer Aided Laser Optics System for Ophthalmic Surgery. Following the dual-use concept, this system is being adapted for clinical use as a retinal treatment system as well as a research tool for military laser-tissue interaction studies. PMID:7654990

  2. Neuroglobin Protection in Retinal Ischemia

    PubMed Central

    Chan, Anita S.Y.; Saraswathy, Sindhu; Rehak, Matus; Ueki, Mari

    2012-01-01

    Purpose. Neuroglobin (Ngb) is a vertebrate globin that is predominantly expressed in the retina and brain. To explore the role of Ngb in retinal neuroprotection during ischemia reperfusion (IR), the authors examined the effect of Ngb overexpression in the retina in vivo by using Ngb-transgenic (Ngb-Tg) mice. Methods. Retinal IR was induced in Ngb overexpressing Ngb-Tg mice and wild type (WT) mice by cannulating the anterior chamber and transiently elevating the IOP for 60 minutes. After Day 7 of reperfusion, the authors evaluated Ngb mRNA and protein expression in nonischemic control as well as ischemic mice and its effect on retinal histology, mitochondrial oxidative stress, and apoptosis, using morphometry and immunohistochemistry, quantitative PCR analysis and Western blot techniques. Results. Ngb-Tg mice without ischemia overexpress Ngb mRNA 11.3-fold (SE ± 0.457, P < 0.05) higher than WT control mice, and this overexpression of Ngb protein was localized to the mitochondria of the ganglion cells, outer and inner plexiform layers, and photoreceptor inner segments. This overexpression of Ngb is associated with decreased mitochondrial DNA damage in Ngb-Tg mice with IR in comparison with WT. Ngb-Tg mice with IR also revealed significant preservation of retinal thickness, significantly less activated caspase 3 protein expression, and apoptosis in comparison with WT mice. Conclusions. Neuroglobin overexpression plays a neuroprotective role against retinal ischemia reperfusion injury due to decreasing of mitochondrial oxidative stress-mediated apoptosis. PMID:22167093

  3. Photoreceptor cell death and rescue in retinal detachment and degenerations

    PubMed Central

    Murakami, Yusuke; Notomi, Shoji; Hisatomi, Toshio; Nakazawa, Toru; Ishibashi, Tatsuro; Miller, Joan W.; Vavvas, Demetrios G.

    2013-01-01

    Photoreceptor cell death is the ultimate cause of vision loss in various retinal disorders, including retinal detachment (RD). Photoreceptor cell death has been thought to occur mainly through apoptosis, which is the most characterized form of programmed cell death. The caspase family of cysteine proteases plays a central role for inducing apoptosis, and in experimental models of RD, dying photoreceptor cells exhibit caspase activation; however, there is a paradox that caspase inhibition alone does not provide a sufficient protection against photoreceptor cell loss, suggesting that other mechanisms of cell death are involved. Recent accumulating evidence demonstrates that non-apoptotic forms of cell death, such as autophagy and necrosis, are also regulated by specific molecular machinery, such as those mediated by autophagy-related proteins and receptor-interacting protein kinases, respectively. Here we summarize the current knowledge of cell death signaling and its roles in photoreceptor cell death after RD and other retinal degenerative diseases. A body of studies indicate that not only apoptotic but also autophagic and necrotic signaling are involved in photoreceptor cell death, and that combined targeting of these pathways may be an effective neuroprotective strategy for retinal diseases associated with photoreceptor cell loss. PMID:23994436

  4. Outer Retinal Structure Following Closed Globe Blunt Ocular Trauma

    PubMed Central

    Flatter, John A.; Cooper, Robert F.; Dubow, Michael J.; Pinhas, Alexander; Singh, Ravi S.; Kapur, Rashmi; Shah, Nishit; Walsh, Ryan D.; Hong, Sang H.; Weinberg, David V.; Stepien, Kimberly E.; Wirostko, William J.; Robison, Scott; Dubra, Alfredo; Rosen, Richard B.; Connor, Thomas B.; Carroll, Joseph

    2014-01-01

    Purpose To evaluate outer retinal structural abnormalities in patients with visual deficits following closed globe blunt ocular trauma (cgBOT). Methods Nine subjects with visual complaints following cgBOT were examined between 1 month post-trauma and 6 years post-trauma. Spectral domain optical coherence tomography (SD-OCT) was used to assess outer retinal architecture, while adaptive optics scanning light ophthalmoscopy (AOSLO) was used to analyze photoreceptor mosaic integrity. Results Visual deficits ranged from central scotomas to decreased visual acuity. SD-OCT defects included focal foveal photoreceptor lesions, variable attenuation of the interdigitation zone, and mottling of the outer segment band, with one subject having normal outer retinal structure. AOSLO revealed disruption of the photoreceptor mosaic in all subjects, variably manifesting as foveal focal discontinuities, perifoveal hyporeflective cones, and paracentral regions of selective cone loss. Conclusions We observe persistent outer retinal disruption in subjects with visual complaints following cgBOT, albeit to a variable degree. AOSLO imaging allows assessment of photoreceptor structure at a level of detail not resolvable using SD-OCT or other current clinical imaging tools. Multimodal imaging appears useful for revealing the cause of visual complaints in patients following cgBOT. Future studies are needed to better understand how photoreceptor structure changes longitudinally in response to various trauma. PMID:24752010

  5. Vinpocetine modulates metabolic activity and function during retinal ischemia.

    PubMed

    Nivison-Smith, Lisa; O'Brien, Brendan J; Truong, Mai; Guo, Cindy X; Kalloniatis, Michael; Acosta, Monica L

    2015-05-01

    Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues. PMID:25696811

  6. [Unusual retinal abnormality: retinal hemorrhages related to scurvy].

    PubMed

    Errera, M-H; Dupas, B; Man, H; Gualino, V; Gaudric, A; Massin, P

    2011-03-01

    A diet restricted to rice and boiled fruit and vegetables leads to vitamin C deficiency. We describe the third case, to our knowledge, of retinal hemorrhages related to scurvy. Reduced bilateral visual acuity in a 50-year-old patient was associated with macrocytic anemia, denutrition, and cutaneous ecchymoses. Oral vitamin C treatment provided subjective clinical improvement and regression of the retinal hemorrhages on fundus examination, with no side effects. Vitamin C plays an important role in collagen stability in vascular and bone walls. PMID:21392843

  7. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on growth and craniofacial proportion

    SciTech Connect

    Schunior, A.; Zengel, A.E.; Mullenix, P.J.; Tarbell, N.J.; Howes, A.; Tassinari, M.S. )

    1990-10-15

    Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions.

  8. Acute and long-lasting effects of peripheral injection of caerulein and CCK-8 on the central GABAergic system in mice.

    PubMed

    Nagahama, H

    1989-01-01

    Acute and long-lasting effects of peripheral injection of caerulein (CLN) and cholecystokinin octapeptide (CCK-8) on the gamma-aminobutylic acid (GABA) content and the GABA accumulation by aminooxyacetic acid (AOAA) in the discrete brain regions of mice were examined. The content and accumulation of GABA in the striatum, hypothalamus, and frontal cortex was measured with high performance liquid chromatography with electrochemical detection (HPLC-ECD). The GABA content slightly decreased in the striatum 60 min after CLN and CCK-8 were administered, whereas it slightly increased in the hypothalamus and frontal cortex. Moreover, with CLN and CCK-8, the GABA accumulation after AOAA treatment decreased in the striatum and hypothalamus 30 min after injection. Meanwhile, when administering CLN, the GABA content as well as the GABA accumulation after AOAA treatment increased in the striatum and frontal cortex 1 day after injection, and continued to increase the second and third day in the striatum. These results showed that peripheral injection of CLN and CCK-8 had effects on the central GABAergic system with local specific actions, and also the long-lasting and time-dependent biphasic effects of CLN. PMID:2622803

  9. Transcorneal Electrical Stimulation Therapy for Retinal Disease

    ClinicalTrials.gov

    2012-05-03

    Retinitis Pigmentosa; Macula Off; Primary Open Angle Glaucoma; Hereditary Macular Degeneration; Treated Retina Detachment; Retinal Artery Occlusion; Retinal Vein Occlusion; Non-Arthritic-Anterior-Ischemic Optic-Neuropathy; Hereditary Autosomal Dominant Optic Atrophy; Dry Age Related Macular Degeneration; Ischemic Macula Edema

  10. Thickness Mapping of Eleven Retinal Layers Segmented Using the Diffusion Maps Method in Normal Eyes

    PubMed Central

    Kafieh, Raheleh; Rabbani, Hossein; Abramoff, Michael D.; Sonka, Milan

    2015-01-01

    This study was conducted to determine the thickness map of eleven retinal layers in normal subjects by spectral domain optical coherence tomography (SD-OCT) and evaluate their association with sex and age. Mean regional retinal thickness of 11 retinal layers was obtained by automatic three-dimensional diffusion map based method in 112 normal eyes of 76 Iranian subjects. We applied our previously reported 3D intraretinal fast layer segmentation which does not require edge-based image information but rather relies on regional image texture. The thickness maps are compared among 9 macular sectors within 3 concentric circles as defined by ETDRS. The thickness map of central foveal area in layers 1, 3, and 4 displayed the minimum thickness. Maximum thickness was observed in nasal to the fovea of layer 1 and in a circular pattern in the parafoveal retinal area of layers 2, 3, and 4 and in central foveal area of layer 6. Temporal and inferior quadrants of the total retinal thickness and most of other quadrants of layer 1 were significantly greater in the men than in the women. Surrounding eight sectors of total retinal thickness and a limited number of sectors in layers 1 and 4 significantly correlated with age. PMID:25960888

  11. Clinical Trials in Retinal Dystrophies

    PubMed Central

    Grob, Seanna R.; Finn, Avni; Papakostas, Thanos D.; Eliott, Dean

    2016-01-01

    Research development is burgeoning for genetic and cellular therapy for retinal dystrophies. These dystrophies are the focus of many research efforts due to the unique biology and accessibility of the eye, the transformative advances in ocular imaging technology that allows for in vivo monitoring, and the potential benefit people would gain from success in the field – the gift of renewed sight. Progress in the field has revealed the immense complexity of retinal dystrophies and the challenges faced by researchers in the development of this technology. This study reviews the current trials and advancements in genetic and cellular therapy in the treatment of retinal dystrophies and also discusses the current and potential future challenges. PMID:26957839

  12. Retinal spot size with wavelength

    NASA Astrophysics Data System (ADS)

    Rockwell, Benjamin A.; Hammer, Daniel X.; Kennedy, Paul K.; Amnotte, Rodney E.; Eilert, Brent; Druessel, Jeffrey J.; Payne, Dale J.; Phillips, Shana L.; Stolarski, David J.; Noojin, Gary D.; Thomas, Robert J.; Cain, Clarence P.

    1997-06-01

    We have made an indirect in-vivo determination of spot size focusing in the rhesus monkey model. Measurement of the laser induced breakdown threshold both in-vitro and in-vivo allow correlation and assignment of a spot size after focusing through the living eye. We discuss and analyze the results and show how trends in minimum visible lesion data should be assessed in light of chromatic aberration. National laser safety standards are based on minimal visual lesion (MVL) threshold studies in different animal models. The energy required for a retinal lesion depends upon may parameters including wavelength and retinal spot size. We attempt to explain trends in reported MVL threshold studies using a model of the eye which allows calculation of changes in retinal spot size due to chromatic aberration.

  13. Diabetes and Retinal Vascular Dysfunction

    PubMed Central

    Shin, Eui Seok; Sorenson, Christine M.; Sheibani, Nader

    2014-01-01

    Diabetes predominantly affects the microvascular circulation of the retina resulting in a range of structural changes unique to this tissue. These changes ultimately lead to altered permeability, hyperproliferation of endothelial cells and edema, and abnormal vascularization of the retina with resulting loss of vision. Enhanced production of inflammatory mediators and oxidative stress are primary insults with significant contribution to the pathogenesis of diabetic retinopathy (DR). We have determined the identity of the retinal vascular cells affected by hyperglycemia, and have delineated the cell autonomous impact of high glucose on function of these cells. We discuss some of the high glucose specific changes in retinal vascular cells and their contribution to retinal vascular dysfunction. This knowledge provides novel insight into the molecular and cellular defects contributing to the development and progression of diabetic retinopathy, and will aid in the development of innovative, as well as target specific therapeutic approaches for prevention and treatment of DR. PMID:25667739

  14. Exploring the retinal connectome

    PubMed Central

    Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Shaw, Margaret V.; Yang, Jia-Hui; DeMill, David; Lauritzen, James S.; Lin, Yanhua; Rapp, Kevin D.; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross

    2011-01-01

    Purpose A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. Methods We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Results Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive

  15. Retinal Image Quality During Accommodation

    PubMed Central

    López-Gil, N.; Martin, J.; Liu, T.; Bradley, A.; Díaz-Muñoz, D.; Thibos, L.

    2013-01-01

    Purpose We asked if retinal image quality is maximum during accommodation, or sub-optimal due to accommodative error, when subjects perform an acuity task. Methods Subjects viewed a monochromatic (552nm), high-contrast letter target placed at various viewing distances. Wavefront aberrations of the accommodating eye were measured near the endpoint of an acuity staircase paradigm. Refractive state, defined as the optimum target vergence for maximising retinal image quality, was computed by through-focus wavefront analysis to find the power of the virtual correcting lens that maximizes visual Strehl ratio. Results Despite changes in ocular aberrations and pupil size during binocular viewing, retinal image quality and visual acuity typically remain high for all target vergences. When accommodative errors lead to sub-optimal retinal image quality, acuity and measured image quality both decline. However, the effect of accommodation errors of on visual acuity are mitigated by pupillary constriction associated with accommodation and binocular convergence and also to binocular summation of dissimilar retinal image blur. Under monocular viewing conditions some subjects displayed significant accommodative lag that reduced visual performance, an effect that was exacerbated by pharmacological dilation of the pupil. Conclusions Spurious measurement of accommodative error can be avoided when the image quality metric used to determine refractive state is compatible with the focusing criteria used by the visual system to control accommodation. Real focusing errors of the accommodating eye do not necessarily produce a reliably measurable loss of image quality or clinically significant loss of visual performance, probably because of increased depth-of-focus due to pupil constriction. When retinal image quality is close to maximum achievable (given the eye’s higher-order aberrations), acuity is also near maximum. A combination of accommodative lag, reduced image quality, and reduced

  16. Retinal Optical Coherence Tomography Imaging

    NASA Astrophysics Data System (ADS)

    Drexler, Wolfgang; Fujimoto, James G.

    The eye is essentially transparent, transmitting light with only minimal optical attenuation and scattering providing easy optical access to the anterior segment as well as the retina. For this reason, ophthalmic and especially retinal imaging has been not only the first but also most successful clinical application for optical coherence tomography (OCT). This chapter focuses on the development of OCT technology for retinal imaging. OCT has significantly improved the potential for early diagnosis, understanding of retinal disease pathogenesis, as well as monitoring disease progression and response to therapy. Development of ultrabroad bandwidth light sources and high-speed detection techniques has enabled significant improvements in ophthalmic OCT imaging performance, demonstrating the potential of three-dimensional, ultrahigh-resolution OCT (UHR OCT) to perform noninvasive optical biopsy of the living human retina, i.e., the in vivo visualization of microstructural, intraretinal morphology in situ approaching the resolution of conventional histopathology. Significant improvements in axial resolution and speed not only enable three-dimensional rendering of retinal volumes but also high-definition, two-dimensional tomograms, topographic thickness maps of all major intraretinal layers, as well as volumetric quantification of pathologic intraretinal changes. These advances in OCT technology have also been successfully applied in several animal models of retinal pathologies. The development of light sources emitting at alternative wavelengths, e.g., around #1,060 nm, not only enabled three-dimensional OCT imaging with enhanced choroidal visualization but also improved OCT performance in cataract patients due to reduced scattering losses in this wavelength region. Adaptive optics using deformable mirror technology, with unique high stroke to correct higher-order ocular aberrations, with specially designed optics to compensate chromatic aberration of the human eye, in

  17. New Wrinkles in Retinal Densitometry

    PubMed Central

    Masella, Benjamin D.; Hunter, Jennifer J.; Williams, David R.

    2014-01-01

    Purpose. Retinal densitometry provides objective information about retinal function. But, a number of factors, including retinal reflectance changes that are not directly related to photopigment depletion, complicate its interpretation. We explore these factors and suggest a method to minimize their impact. Methods. An adaptive optics scanning light ophthalmoscope (AOSLO) was used to measure changes in photoreceptor reflectance in monkeys before and after photopigment bleaching with 514-nm light. Reflectance measurements at 514 nm and 794 nm were recorded simultaneously. Several methods of normalization to extract the apparent optical density of the photopigment were compared. Results. We identified stimulus-related fluctuations in 794-nm reflectance that are not associated with photopigment absorptance and occur in both rods and cones. These changes had a magnitude approaching those associated directly with pigment depletion, precluding the use of infrared reflectance for normalization. We used a spatial normalization method instead, which avoided the fluctuations in the near infrared, as well as a confocal AOSLO designed to minimize light from layers other than the receptors. However, these methods produced a surprisingly low estimate of the apparent rhodopsin density (animal 1: 0.073 ± 0.006, animal 2: 0.032 ± 0.003). Conclusions. These results confirm earlier observations that changes in photopigment absorption are not the only source of retinal reflectance change during dark adaptation. It appears that the stray light that has historically reduced the apparent density of cone photopigment in retinal densitometry arises predominantly from layers near the photoreceptors themselves. Despite these complications, this method provides a valuable, objective measure of retinal function. PMID:25316726

  18. Preservation of retinal structure and function after cilioretinal artery occlusion: a case report.

    PubMed

    Brown, Craig J

    2016-01-01

    Cilioretinal artery occlusion is a cause of sudden, often catastrophic loss of central vision. There are no established effective treatments. Recently, a patient presented 24 hours after a cilioretinal artery occlusion, following a cardiac catheterization prior to which her blood thinners had been discontinued. Lacking an effective way to address the severe retinal ischemic oxidative stress, she was offered, under compassionate use, a multivitamin complex designed to address retinal ischemia and oxidative stress. Significant components of this product are L-methylfolate and n-acetyl cysteine. The patient experienced a rapid unexpected improvement in vision and preservation of retinal structure, suggesting that marked improvement in retinal artery occlusions outcomes may be possible as late as 24 hours postocclusion. This is the third reported case of cilioretinal artery occlusion associated with cardiac catheterization. PMID:26929671

  19. Preservation of retinal structure and function after cilioretinal artery occlusion: a case report

    PubMed Central

    Brown, Craig J

    2016-01-01

    Cilioretinal artery occlusion is a cause of sudden, often catastrophic loss of central vision. There are no established effective treatments. Recently, a patient presented 24 hours after a cilioretinal artery occlusion, following a cardiac catheterization prior to which her blood thinners had been discontinued. Lacking an effective way to address the severe retinal ischemic oxidative stress, she was offered, under compassionate use, a multivitamin complex designed to address retinal ischemia and oxidative stress. Significant components of this product are L-methylfolate and n-acetyl cysteine. The patient experienced a rapid unexpected improvement in vision and preservation of retinal structure, suggesting that marked improvement in retinal artery occlusions outcomes may be possible as late as 24 hours postocclusion. This is the third reported case of cilioretinal artery occlusion associated with cardiac catheterization. PMID:26929671

  20. Progressive retinal detachment secondary to juxtapapillary microholes in association with type 3 posterior staphylomas

    PubMed Central

    Dinah, Christiana B; Vaideanu-Collins, Daniela; Steel, David HW

    2014-01-01

    Purpose This study describes a novel subtype of retinal detachment occurring in eyes with pathological myopia associated with type 3 posterior staphyloma and discusses the management options. Methods We retrospectively reviewed the case notes of seven patients who presented with unilateral symptomatic rhegmatogenous retinal detachment secondary to nasal juxtapapillary microholes. Results All seven patients had pathological myopia and an associated peripapillary type 3 posterior staphyloma. They all presented with symptoms of acute posterior vitreous detachment and had progressive retinal detachment. All cases were discovered to have a single juxtapapillary hole less than 1 disc diameter from the optic-nerve head, within areas of nasal chorioretinal atrophy. The microholes were identified intraoperatively in six of seven cases, with one case identified preoperatively on optical coherence tomography. In the four most recent cases, successful retinal reattachment was achieved with vitrectomy and C2F6 gas tamponade. The remaining three cases were managed with vitrectomy and silicone oil. Conclusion Seven patients with pathological myopia, type 3 posterior staphyloma, and progressive retinal detachment secondary to juxtapapillary microholes are presented in this paper. High clinical suspicion is required to identify these breaks. Successful retinal reattachment with pars plana vitrectomy and long-acting gas is possible. PMID:24959066

  1. Constitutive Overexpression of Human Erythropoietin Protects the Mouse Retina against Induced But Not Inherited Retinal Degeneration

    PubMed Central

    Grimm, Christian; Wenzel, Andreas; Stanescu, Dinu; Samardzija, Marijana; Hotop, Svenja; Groszer, Mathias; Naash, Muna; Gassmann, Max; Remé, Charlotte

    2010-01-01

    Elevation of erythropoietin (Epo) concentrations by hypoxic preconditioning or application of recombinant human Epo (huEpo) protects the mouse retina against light-induced degeneration by inhibiting photoreceptor cell apoptosis. Because photoreceptor apoptosis is also the common path to cell loss in retinal dystrophies such as retinitis pigmentosa (RP), we tested whether high levels of huEpo would reduce apoptotic cell death in two mouse models of human RP. We combined the two respective mutant mouse lines with a transgenic line (tg6) that constitutively overexpresses huEpo mainly in neural tissues. Transgenic expression of huEpo caused constitutively high levels of Epo in the retina and protected photoreceptors against light-induced degeneration; however, the presence of high levels of huEpo did not affect the course or the extent of retinal degeneration in a light-independent (rd1) and a light-accelerated (VPP) mouse model of RP. Similarly, repetitive intraperitoneal injections of recombinant huEpo did not protect the retina in the rd1 and the VPP mouse. Lack of neuroprotection by Epo in the two models of inherited retinal degeneration was not caused by adaptational downregulation of Epo receptor. Our results suggest that apoptotic mechanisms during acute, light-induced photoreceptor cell death differ from those in genetically based retinal degeneration. Therapeutic intervention with cell death in inherited retinal degeneration may therefore require different drugs and treatments. PMID:15215287

  2. Tuberculous Panophthalmitis with Lymphadenitis and Central Nervous System Tuberculoma

    PubMed Central

    Srichatrapimuk, Sirawat; Wattanatranon, Duangkamon

    2016-01-01

    Tuberculosis (TB) is a serious infectious disease that spreads globally. The ocular manifestations of TB are uncommon and diverse. TB panophthalmitis has been rarely reported. Here, we described a 38-year-old Thai man presenting with panophthalmitis of the right eye. Further investigation showed that he had concurrent TB lymphadenitis and central nervous system (CNS) tuberculoma, as well as HIV infection, with a CD4 cell count of 153 cells/mm3. Despite the initial response to antituberculous agents, the disease had subsequently progressed and enucleation was required. The pathological examination revealed acute suppurative granulomatous panophthalmitis with retinal detachment. Further staining demonstrated acid-fast bacilli in the tissue. Colonies of Mycobacterium tuberculosis were obtained from tissue culture. He was treated with antiretroviral agents for HIV infection and 12 months of antituberculous agents. Clinicians should be aware of the possibility of TB in the differential diagnosis of endophthalmitis and panophthalmitis, especially in regions where TB is endemic. PMID:27051539

  3. Tyro3 Modulates Mertk-Associated Retinal Degeneration

    PubMed Central

    Vollrath, Douglas; Yasumura, Douglas; Benchorin, Gillie; Matthes, Michael T.; Feng, Wei; Nguyen, Natalie M.; Sedano, Cecilia D.; Calton, Melissa A.; LaVail, Matthew M.

    2015-01-01

    Inherited photoreceptor degenerations (IPDs) are the most genetically heterogeneous of Mendelian diseases. Many IPDs exhibit substantial phenotypic variability, but the basis is usually unknown. Mutations in MERTK cause recessive IPD phenotypes associated with the RP38 locus. We have identified a murine genetic modifier of Mertk-associated photoreceptor degeneration, the C57BL/6 (B6) allele of which acts as a suppressor. Photoreceptors degenerate rapidly in Mertk-deficient animals homozygous for the 129P2/Ola (129) modifier allele, whereas animals heterozygous for B6 and 129 modifier alleles exhibit an unusual intermixing of degenerating and preserved retinal regions, with females more severely affected than males. Mertk-deficient mice homozygous for the B6 modifier allele display degeneration only in the far periphery, even at 8 months of age, and have improved retinal function compared to animals homozygous for the 129 allele. We genetically mapped the modifier to an approximately 2-megabase critical interval that includes Tyro3, a paralog of Mertk. Tyro3 expression in the outer retina varies with modifier genotype in a manner characteristic of a cis-acting expression quantitative trait locus (eQTL), with the B6 allele conferring an approximately three-fold higher expression level. Loss of Tyro3 function accelerates the pace of photoreceptor degeneration in Mertk knockout mice, and TYRO3 protein is more abundant in the retinal pigment epithelium (RPE) adjacent to preserved central retinal regions of Mertk knockout mice homozygous for the B6 modifier allele. Endogenous human TYRO3 protein co-localizes with nascent photoreceptor outer segment (POS) phagosomes in a primary RPE cell culture assay, and expression of murine Tyro3 in cultured cells stimulates phagocytic ingestion of POS. Our findings demonstrate that Tyro3 gene dosage modulates Mertk-associated retinal degeneration, provide strong evidence for a direct role for TYRO3 in RPE phagocytosis, and suggest

  4. Retinal Remodeling and Metabolic Alterations in Human AMD

    PubMed Central

    Jones, Bryan W.; Pfeiffer, Rebecca L.; Ferrell, William D.; Watt, Carl B.; Tucker, James; Marc, Robert E.

    2016-01-01

    Age-related macular degeneration (AMD) is a progressive retinal degeneration resulting in central visual field loss, ultimately causing debilitating blindness. AMD affects 18% of Americans from 65 to 74, 30% older than 74 years of age and is the leading cause of severe vision loss and blindness in Western populations. While many genetic and environmental risk factors are known for AMD, we currently know less about the mechanisms mediating disease progression. The pathways and mechanisms through which genetic and non-genetic risk factors modulate development of AMD pathogenesis remain largely unexplored. Moreover, current treatment for AMD is palliative and limited to wet/exudative forms. Retina is a complex, heterocellular tissue and most retinal cell classes are impacted or altered in AMD. Defining disease and stage-specific cytoarchitectural and metabolic responses in AMD is critical for highlighting targets for intervention. The goal of this article is to illustrate cell types impacted in AMD and demonstrate the implications of those changes, likely beginning in the retinal pigment epithelium (RPE), for remodeling of the the neural retina. Tracking heterocellular responses in disease progression is best achieved with computational molecular phenotyping (CMP), a tool that enables acquisition of a small molecule fingerprint for every cell in the retina. CMP uncovered critical cellular and molecular pathologies (remodeling and reprogramming) in progressive retinal degenerations such as retinitis pigmentosa (RP). We now applied these approaches to normal human and AMD tissues mapping progression of cellular and molecular changes in AMD retinas, including late-stage forms of the disease. PMID:27199657

  5. Suppression and retinal correspondence in intermittent exotropia.

    PubMed Central

    Cooper, J; Record, C D

    1986-01-01

    Suppression scotomas and retinal projection (retinal correspondence) were measured in six intermittent exotropes during deviation. Measurements used red-green anaglyph stimuli presented on a black background which could be varied from 3.4 minutes of arc to 3 degrees 24'. Results showed non-suppression of all points between the fovea and the diplopia point. Harmonious anomalous retinal correspondence was usually observed. Two subjects had spontaneous changes from anomalous retinal correspondence to normal retinal correspondence without a concurrent change in ocular position. Conventional testing resulted in more variable results in regard to retinal correspondence and suppression, suggesting that non-suppression and anomalous retinal correspondence occur when black backgrounds are used for testing. PMID:3756124

  6. Retinitis Pigmentosa and Education Issues

    ERIC Educational Resources Information Center

    Brown, Thomas J.

    2005-01-01

    Retinitis Pigmentosa includes a number of inherited diseases which usually result in blindness. The disease is progressive in nature and begins with the deterioration of cells in the eye responsible for peripheral vision. As the condition worsens there is a gradual loss of peripheral vision and night blindness. Proper educational planning requires…

  7. Detection of localized retinal malfunction in retinal degeneration model using a multielectrode array system.

    PubMed

    Homma, Kohei; Osakada, Fumitaka; Hirami, Yasuhiko; Jin, Zi-Bing; Mandai, Michiko; Takahashi, Masayo

    2009-07-01

    Light stimulation inhibits the retinal dark current through phototransduction signals in the photoreceptors. Electroretinography (ERG) detects the blockage of the dark current as the a-wave of the ERG. However, standard ERGs represent the summed neural activity of the retina, and information on localized functions cannot be obtained. In this study, we used a multielectrode array (MEA) system and directly recorded the focal activities of the photoreceptors of the retina. Retinas were isolated from dark-adapted rodents and were draped over the electrode array with vitreal surface of the retina on the electrode array. After light stimulation, negative waves were recorded from each electrode. Adding aminobutyric acid, a selective agonist of mGluR6 expressed on ON-bipolar cells, to the media did not block the generation of the responses. The amplitude of the response increased with increasing retinal development. When the retina was locally injured, light-elicited responses were diminished only in the injured areas of the retina. Retinas isolated from rats given N-methyl-N-nitrosourea (MNU) were also tested. In central retinas of MNU-treated rats, the responses were progressively decreased following injection of MNU. In contrast, in the peripheral retinas, amplitude of the responses was relatively retained, consistent with the retinal thickness observed by immunohistochemistry. In conclusion, light-evoked responses were recorded with the MEA system. The MEA system was useful for detecting subtle and focal activation of photoreceptors. This spatial information should be valuable in investigating local functional recovery in therapeutically treated areas, such as in gene transfer or cell transplantation. PMID:19224574

  8. The lymphoid chemokine, CXCL13, is dispensable for the initial recruitment of B cells to the acutely inflamed central nervous system

    PubMed Central

    Rainey-Barger, Emily K; Rumble, Julie M; Lalor, Stephen J.; Esen, Nilufer; Segal, Benjamin M; Irani, David N

    2010-01-01

    Cases of progressive multifocal leukoencephalopathy can occur in patients treated with the B cell depleting anti-CD20 antibody, rituximab, highlighting the importance of B cell surveillance of the central nervous system (CNS). The lymphoid chemokine, CXCL13, is critical for B cell recruitment and functional organization of peripheral lymphoid tissues, and CXCL13 levels are often elevated in the inflamed CNS. To more directly investigate the role of CXCL13 in CNS B cell migration, its role in animal models of infectious and inflammatory demyelinating disease was examined. During acute alphavirus encephalitis where viral clearance depends on the local actions of anti-viral antibodies, CXCL13 levels and B cell numbers increased in brain tissue over time. Surprisingly, however, CXCL13-deficient animals showed normal CNS B cell recruitment, unaltered CNS virus replication and clearance, and intact peripheral anti-viral antibody responses. During experimental autoimmune encephalomyelitis (EAE), CNS levels of CXCL13 increased as symptoms emerged and equivalent numbers of B cells were identified among the CNS infiltrates of CXCL13-deficient mice compared to control animals. However, CXCL13-deficient mice did not sustain pathogenic anti-myelin T cell responses, consistent with their known propensity to develop more self-limited EAE. These data show that CXCL13 is dispensable for CNS B cell recruitment in both models. The disease course is unaffected by CXCL13 in a CNS infection paradigm that depends on a pathogen-specific B cell response, while it is heightened and prolonged by CXCL13 when myelin-specific CD4+ T cells drive CNS pathology. Thus, CXCL13 could be a therapeutic target in certain neuroinflammatory diseases, but not by blocking B cell recruitment to the CNS. PMID:20933590

  9. Impact of Cranial Irradiation Added to Intrathecal Conditioning in Hematopoietic Cell Transplantation in Adult Acute Myeloid Leukemia With Central Nervous System Involvement

    SciTech Connect

    Mayadev, Jyoti S.; Douglas, James G.; Storer, Barry E.; Appelbaum, Frederick R.; Storb, Rainer

    2011-05-01

    Purpose: Neither the prognostic importance nor the appropriate management of central nervous system (CNS) involvement is known for patients with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT). We examined the impact of a CNS irradiation boost to standard intrathecal chemotherapy (ITC). Methods and Materials: From 1995 to 2005, a total of 648 adult AML patients received a myeloablative HCT: 577 patients were CNS negative (CNS-), and 71 were CNS positive (CNS+). Of the 71 CNS+ patients, 52 received intrathecal chemotherapy alone (CNS+ITC), and 19 received ITC plus an irradiation boost (CNS+RT). Results: The CNS-, CNS+ITC, and CNS+RT patients had 1- and 5-year relapse-free survivals (RFS) of 43% and 35%, 15% and 6%, and 37% and 32%, respectively. CNS+ITC patients had a statistically significant worse RFS compared with CNS- patients (hazard ratio [HR], 2.65; 95% confidence interval [CI], 2.0-3.6; p < 0.0001). CNS+RT patients had improved relapse free survival over that of CNS+ITC patients (HR, 0.45; 95% CI, 0.2-0.8; p = 0.01). The 1- and 5-year overall survivals (OS) of patients with CNS-, CNS+ITC, and CNS+RT, were 50% and 38%, 21% and 6%, and 53% and 42%, respectively. The survival of CNS+RT were significantly better than CNS+ITC patients (p = 0.004). After adjusting for known risk factors, CNS+RT patients had a trend toward lower relapse rates and reduced nonrelapse mortality. Conclusions: CNS+ AML is associated with a poor prognosis. The role of a cranial irradiation boost to intrathecal chemotherapy appears to mitigate the risk of CNS disease, and needs to be further investigated to define optimal treatment strategies.

  10. The comparison of stroke volume variation with central venous pressure in predicting fluid responsiveness in septic patients with acute circulatory failure

    PubMed Central

    Angappan, Santhalakshmi; Parida, Satyen; Vasudevan, Arumugam; Badhe, Ashok Shankar

    2015-01-01

    Purpose: The present study was designed to investigate the efficacy of stroke volume variation (SVV) in predicting fluid responsiveness and compare it to traditional measures of volume status assessment like central venous pressure (CVP). Methods: Forty-five mechanically ventilated patients in sepsis with acute circulatory failure. Patients were not included when they had atrial fibrillation, other severe arrhythmias, permanent pacemaker, or needed mechanical cardiac support. Furthermore, excluded were patients with hypoxemia and a CVP >12. Patients received volume expansion in the form of 500 ml of 6% hydroxyethyl starch. Results: The volume expansion-induced increase in  cardiac index (CI) was >15% in 29 patients (labeled responders) and <15% in 16 patients (labeled nonresponders). Before volume expansion, SVV was higher in responders than in nonresponders. Receiver operating characteristic curves analysis showed that SVV was a more accurate indicator of fluid responsiveness than CVP. Before volume expansion, an SVV value of 13% allowed discrimination between responders and nonresponders with a sensitivity of 78% and a specificity of 89%. Volume expansion-induced changes in CI weakly and positively correlated with SVV before volume expansion. Volume expansion decreased SVV from 18.86 ± 4.35 to 7.57 ± 1.80 and volume expansion-induced changes in SVV moderately correlated with volume expansion-induced changes in CI. Conclusions: When predicting fluid responsiveness in mechanically ventilated patients in septic shock, SVV is more effective than CVP. Nevertheless, the overall correlation of baseline SVV with increases in CI remains poor. Trends in SVV, as reflected by decreases with volume replacement, seem to correlate much better with increases in CI. PMID:26180432

  11. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993

    PubMed Central

    Lazarus, Hillard M.; Richards, Susan M.; Chopra, Raj; Litzow, Mark R.; Burnett, Alan K.; Wiernik, Peter H.; Franklin, Ian M.; Tallman, Martin S.; Cook, Lucy; Buck, Georgina; Durrant, I. Jill; Rowe, Jacob M.; Goldstone, Anthony H.

    2006-01-01

    Outcome of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) disease at diagnosis is unclear. We treated 1508 de novo ALL patients with 2-phase induction and then high-dose methotrexate with l-asparaginase. Patients up to 50 years old in first remission (CR1) with a matched related donor (MRD) underwent an allogeneic stem cell transplantation (SCT); the remainder in CR1 were randomized to an autologous SCT or intensive consolidation followed by maintenance chemotherapy. Philadelphia chromosome (Ph)–positive patients were offered a matched unrelated donor (MUD) allogeneic SCT. Seventy-seven of 1508 (5%) patients a median age of 29 years had CNS leukemia at presentation; 13 of the 77 (17%) had Ph-positive ALL. Sixty-nine of 77 (90%) patients attained CR1. Thirty-six patients underwent transplantation in CR1 (25 MRD, 5 MUD, and 6 autografts). Eleven of 25 patients with MRD transplantation remain alive at 21 to 102 months, 2 of 5 with MUD at 42 and 71 months, and 1 of 6 with autologous SCT at 35 months. Seven of 27 treated with consolidation/maintenance remain in CR1 56 to 137 months after diagnosis. Overall survival at 5 years was 29% in those with CNS involvement at diagnosis versus 38% (P = .03) for those without. CNS leukemia in adult ALL is uncommon at diagnosis. Adult Ph-negative ALL patients, however, can attain long-term disease-free survival using SCT as well as conventional chemotherapy. PMID:16556888

  12. [Effects of oxygen and nikethamide on central drive, ventilation and blood gases of patients with obstructive lung disease in acute exacerbation of respiratory failure].

    PubMed

    Ren, X H; Ding, D J; Chen, E Z

    1993-12-01

    Twelve subjects with COPD in acute exacerbation of respiratory failure were studied. The experiment of each subject was divided into three steps: room air breathing, 35% O2 inhalation for one hour, and then intravenous drip of nikethamide (1.875g) for two hours with 35% oxygen inhalation at the same time. At the end of each step, mouth occlusion pressure (P0.1), VT, VE, VA, VCO2, VD and PaO2, PaCO2 were measured respectively. The results showed that, when breathing air, all the patients presented significant higher P0.1 than normal subjects, indicated higher central drive. After oxygen inhalation, P0.1 decreased markedly, but still higher than normal. No correlation was found between delta P0.1 and delta PaO2. VE declined with the drop of P0.1, but this was due to a decrease of respiratory frequency, while VA remained unchanged (P > 0.05). The increase of PaCO2 was unremarkable. Neither correlation was found between delta VA and delta P0.1, nor between delta VA and delta PaCO2. However, a close correlation existed between delta VCO2/VCO2 and delta VE/VE. The result of our study is not consistent with the postulation, the removal of the hypoxic stimulate after oxygen administration results in a decrease of ventilation and CO2 retention. After nikethamide administration, P0.1 increased as well as VE while VA and PaCO2 remained unchanged. The increase of VE was caused by the increase of respiratory rate. Furthermore, PaO2 decreased in some patients. All of the changes demonstrated that nothing is worthwhile with the treatment of nikethamide, but a side effect from increasing work of breathing and consumption of oxygen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8033228

  13. Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma

    NASA Astrophysics Data System (ADS)

    Schori, Hadas; Kipnis, Jonathan; Yoles, Eti; Woldemussie, Elizabeth; Ruiz, Guadalupe; Wheeler, Larry A.; Schwartz, Michal

    2001-03-01

    Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 ± 270 and 1,329 ± 121, respectively, mean ± SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 ± 101 compared with 1,414 ± 36; P <0.05), but not when they were immunized 48h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8%±6.8% to 4.3%±1.6%, without affecting the intraocular pressure

  14. Optimizing the treatment of rhegmatogenous retinal detachment.

    PubMed

    Hajari, Javad Nouri

    2016-03-01

    Surgical approaches for rhegmatogenous retinal detachment (RRD) have evolved rapidly in the past century. This has resulted in an increase in the anatomical success rate from zero per cent in the beginning of the 1900s to now almost 100 per cent. Rhegmatogenous retinal detachment is regarded as an acute eye disease that needs immediate treatment. With the increasing number of cataract surgeries and an increased elderly population, the numbers of RRD occurrences are increasing. The aim of this thesis is to create knowledge on how treatment and care of RRD patients can be optimized. In the first paper, data on the incidence of RRD in Denmark are presented based on data from a nation register the National Patient Registry (NPR). It was discovered that the incidence of RRD in Denmark is similar to previous reported numbers and that the incidence has been increasing due to increasing numbers of cataract surgeries and an increased elderly population. Using data from the NPR, we estimated that the risk of a RRD occurring on the fellow eye is 100 times larger than on the first eye and that middle aged men have the highest risk. Having an increase in the incidence of RRD we need to ensure that the patients are also treated in the most optimal way. To ensure this, an indicator is needed to monitor the quality at the different centres. This indicator presented in the second paper is based in the occurrence of redetachment. We define a detachment to be caused by poor surgery if the retina detaches within one year after initial surgery with pneumatic retinopexy, scleral buckling and VTX with gas, and one and a half years after surgery with VTX with oil. Also lack of oil removal within the first year is a failed operation. It is widely accepted that RRD is an acute disease but when should surgery be performed to attain the most optimal result? In the third paper, we evaluated the progression of posterior RRD with an optical coherence tomography to make an objective assessment of

  15. Relation between retinal vein occlusions and axial length.

    PubMed Central

    Aritürk, N.; Oge, Y.; Erkan, D.; Süllü, Y.; Mohajerý, F.

    1996-01-01

    AIMS: To evaluate the ocular axial length as a risk factor for development of central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). METHODS: Ocular axial lengths were measured, by A-scan ultrasonography, in 17 patients with CRVO and 41 patients with BRVO and compared with those of contralateral unaffected eyes and 66 age matched controls. RESULTS: In 17 patients with CRVO the mean axial length of affected eyes was 22.25 (SD 0.19) mm and of unaffected eyes was 22.61 (0.13) mm. In 41 patients with BRVO the mean axial length of affected eyes was 22.89 (0.11) mm and of unaffected eyes was 22.99 (0.12) mm. CONCLUSION: These findings confirm that the axial lengths in CRVO and BRVO were significantly shorter than in the controls. This significant difference may be a risk factor in the development of CRVO and BRVO. PMID:8795376

  16. Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa.

    PubMed

    Wang, Wei; Lee, Sang Joon; Scott, Patrick A; Lu, Xiaoqin; Emery, Douglas; Liu, Yongqin; Ezashi, Toshihiko; Roberts, Michael R; Ross, Jason W; Kaplan, Henry J; Dean, Douglas C

    2016-04-12

    Most retinitis pigmentosa (RP) mutations arise in rod photoreceptor genes, leading to diminished peripheral and nighttime vision. Using a pig model of autosomal-dominant RP, we show glucose becomes sequestered in the retinal pigment epithelium (RPE) and, thus, is not transported to photoreceptors. The resulting starvation for glucose metabolites impairs synthesis of cone visual pigment-rich outer segments (OSs), and then their mitochondrial-rich inner segments dissociate. Loss of these functional structures diminishes cone-dependent high-resolution central vision, which is utilized for most daily tasks. By transplanting wild-type rods, to restore glucose transport, or directly replacing glucose in the subretinal space, to bypass its retention in the RPE, we can regenerate cone functional structures, reactivating the dormant cells. Beyond providing metabolic building blocks for cone functional structures, we show glucose induces thioredoxin-interacting protein (Txnip) to regulate Akt signaling, thereby shunting metabolites toward aerobic glucose metabolism and regenerating cone OS synthesis. PMID:27050517

  17. A rare case of branch retinal vein occlusion following Sirsasana.

    PubMed

    Balamurugan, Anugraha; Srikanth, Krishnagopal

    2016-01-01

    Sirsasana is a type of headstand postural yoga in which the body is completely inverted. It is performed with or without wall support. In this position, the body is held upright supported by the forearms, while the crown of the head rests lightly on the floor. This is an advanced pose and should be attempted under the supervision of a qualified yoga instructor. The practice of Sirsasana is postulated to increase blood flow to the brain, improving memory, and other intellectual functions. It is also known to cause causes raised intraocular pressure, decompression retinopathy, glaucomatous visual field defects, central retinal vein occlusion, progression of glaucoma, optic neuropathy, and conjunctival varix thrombosis. We report a case of branch retinal vein occlusion following Sirsasana in a patient with systemic hypertension. PMID:27512326

  18. A rare case of branch retinal vein occlusion following Sirsasana

    PubMed Central

    Balamurugan, Anugraha; Srikanth, Krishnagopal

    2016-01-01

    Sirsasana is a type of headstand postural yoga in which the body is completely inverted. It is performed with or without wall support. In this position, the body is held upright supported by the forearms, while the crown of the head rests lightly on the floor. This is an advanced pose and should be attempted under the supervision of a qualified yoga instructor. The practice of Sirsasana is postulated to increase blood flow to the brain, improving memory, and other intellectual functions. It is also known to cause causes raised intraocular pressure, decompression retinopathy, glaucomatous visual field defects, central retinal vein occlusion, progression of glaucoma, optic neuropathy, and conjunctival varix thrombosis. We report a case of branch retinal vein occlusion following Sirsasana in a patient with systemic hypertension. PMID:27512326

  19. [Morphologic aspects of therapy-resistant cytomegalovirus retinitis].

    PubMed

    Meyer, P; Bernauer, W; Daicker, B; Zimmerli, W; Rüttimann, S

    1992-05-01

    Intravenous ganciclovir treatment was performed in eight male AIDS patients with primary unilateral CMV-retinitis. Three patients developed slowly progressive CMV-retinitis in the fellow eye despite adequate dose of ganciclovir. These different CMV-manifestations are shown in a sequence of fundus pictures. Three types of CMV-lesions were observed in connection with this study. Untreated central lesions showed the aspect of crumbled cheese and ketchup. Untreated lesions in the peripherie were yellowish-white, granular, "dry" and showed in most cases no haemorrhages. Lesions appearing during treatment showed initially "dry" white opaque subretinal areas, turning later on to the typical aspect of untreated lesions. The progression could not be stopped by highdose ganciclovir i.v. and thus bilateral blindness resulted after 12 to 22 months. The level of CD4-lymphocytes in the blood was diminished in all patients, but much more in patients with progressive disease. PMID:1319528

  20. Two-Step Reactivation of Dormant Cones in Retinitis Pigmentosa

    PubMed Central

    Wang, Wei; Lee, Sang Joon; Scott, Patrick A.; Lu, Xiaoqin; Emery, Douglas; Liu, Yongqin; Ezashi, Toshihiko; Roberts, Michael R.; Ross, Jason W.; Kaplan, Henry J.; Dean, Douglas C.

    2016-01-01

    Most Retinitis Pigmentosa (RP) mutations arise in rod photoreceptor genes, leading to diminished peripheral and nightime vision. Using a pig model of autosomal-dominant RP, we show glucose becomes sequestered in the retinal pigment epithelium (RPE), and thus is not transported to photoreceptors. The resulting starvation for glucose metabolites impairs synthesis of cone visual pigment -rich outer segments (OS), and then their mitochondrial-rich inner segments dissociate. Loss of these functional structures diminishes cone-dependent high-resolution central vision, which is utilized for most daily tasks. By transplanting wild-type rods, to restore glucose transport, or directly replacing glucose in the subretinal space, to bypass its retention in the RPE, we can regenerate cone functional structures, reactivating the dormant cells. Beyond providing metabolic building blocks for cone functional structures, we show glucose induces thioredoxin-interacting protein (Txnip) to regulate Akt signaling, thereby shunting metabolites toward aerobic glucose metabolism and regenerating cone OS synthesis. PMID:27050517

  1. Air Pollution and the Microvasculature: A Cross-Sectional Assessment of In Vivo Retinal Images in the Population-Based Multi-Ethnic Study of Atherosclerosis (MESA)

    PubMed Central

    Adar, Sara D.; Klein, Ronald; Klein, Barbara E. K.; Szpiro, Adam A.; Cotch, Mary Frances; Wong, Tien Y.; O'Neill, Marie S.; Shrager, Sandi; Barr, R. Graham; Siscovick, David S.; Daviglus, Martha L.; Sampson, Paul D.; Kaufman, Joel D.

    2010-01-01

    Background Long- and short-term exposures to air pollution, especially fine particulate matter (PM2.5), have been linked to cardiovascular morbidity and mortality. One hypothesized mechanism for these associations involves microvascular effects. Retinal photography provides a novel, in vivo approach to examine the association of air pollution with changes in the human microvasculature. Methods and Findings Chronic and acute associations between residential air pollution concentrations and retinal vessel diameters, expressed as central retinal arteriolar equivalents (CRAE) and central retinal venular equivalents (CRVE), were examined using digital retinal images taken in Multi-Ethnic Study of Atherosclerosis (MESA) participants between 2002 and 2003. Study participants (46 to 87 years of age) were without clinical cardiovascular disease at the baseline examination (2000–2002). Long-term outdoor concentrations of PM2.5 were estimated at each participant's home for the 2 years preceding the clinical exam using a spatio-temporal model. Short-term concentrations were assigned using outdoor measurements on the day preceding the clinical exam. Residential proximity to roadways was also used as an indicator of long-term traffic exposures. All associations were examined using linear regression models adjusted for subject-specific age, sex, race/ethnicity, education, income, smoking status, alcohol use, physical activity, body mass index, family history of cardiovascular disease, diabetes status, serum cholesterol, glucose, blood pressure, emphysema, C-reactive protein, medication use, and fellow vessel diameter. Short-term associations were further controlled for weather and seasonality. Among the 4,607 participants with complete data, CRAE were found to be narrower among persons residing in regions with increased long- and short-term levels of PM2.5. These relationships were observed in a joint exposure model with −0.8 µm (95% confidence interval [CI] −1.1 to −0

  2. Pharmacologic vitreolysis with ocriplasmin: rationale for use and therapeutic potential in vitreo-retinal disorders.

    PubMed

    Khoshnevis, Matin; Sebag, J

    2015-04-01

    With increased knowledge about the origins and pathophysiology of vitreo-retinal disorders—and, in particular, the central role of anomalous posterior vitreous detachment in vitreo-maculopathies—a paradigm shift from surgery to pharmacotherapy is taking place with the development of pharmacologic vitreolysis. The first approved agent for pharmacologic vitreolysis therapy is ocriplasmin, a truncated form of the nonspecific serine protease plasmin. Twelve studies comprise the current ocriplasmin clinical trial program, demonstrating the efficacy and safety of a single intravitreal injection of ocriplasmin for the treatment of patients with symptomatic vitreo-macular adhesion or vitreo-macular traction, including patients with macular holes. Although post-approval implementation of ocriplamsin in clinical practice has shown success rates of up to 78%, there have been recent case reports of acute, transient visual dysfunction. There are thus new initiatives to further refine clinical indications for case selection and to identify possible untoward effects. Although more studies are warranted, it appears that ocriplasmin offers a good alternative to surgery. The future lies in pharmacologic vitreolysis, and the future of pharmacologic vitreolysis lies in prevention. Thus, long-term studies are needed to define a role for pharmacologic vitreolysis, in particular with ocriplasmin, in the prevention of progressive diabetic retinopathy and age-related macular degeneration. PMID:25812991

  3. Retinal vasculature classification using novel multifractal features

    NASA Astrophysics Data System (ADS)

    Ding, Y.; Ward, W. O. C.; Duan, Jinming; Auer, D. P.; Gowland, Penny; Bai, L.

    2015-11-01

    Retinal blood vessels have been implicated in a large number of diseases including diabetic retinopathy and cardiovascular diseases, which cause damages to retinal blood vessels. The availability of retinal vessel imaging provides an excellent opportunity for monitoring and diagnosis of retinal diseases, and automatic analysis of retinal vessels will help with the processes. However, state of the art vascular analysis methods such as counting the number of branches or measuring the curvature and diameter of individual vessels are unsuitable for the microvasculature. There has been published research using fractal analysis to calculate fractal dimensions of retinal blood vessels, but so far there has been no systematic research extracting discriminant features from retinal vessels for classifications. This paper introduces new methods for feature extraction from multifractal spectra of retinal vessels for classification. Two publicly available retinal vascular image databases are used for the experiments, and the proposed methods have produced accuracies of 85.5% and 77% for classification of healthy and diabetic retinal vasculatures. Experiments show that classification with multiple fractal features produces better rates compared with methods using a single fractal dimension value. In addition to this, experiments also show that classification accuracy can be affected by the accuracy of vessel segmentation algorithms.

  4. Retinal ganglion cell axons regenerate in the presence of intact sensory fibres.

    PubMed

    King, Carolyn; Bartlett, Carole; Sauvé, Yves; Lund, Ray; Dunlop, Sarah; Beazley, Lyn

    2006-02-01

    A novel allograft paradigm was used to test whether adult mammalian central axons regenerate within a peripheral nerve environment containing intact sensory axons. Retinal ganglion cell axon regeneration was compared following anastomosis of dorsal root ganglia grafts or conventional peripheral nerve grafts to the adult rat optic nerve. Dorsal root ganglia grafts comprised intact sensory and degenerate motor axons, whereas conventional grafts comprised both degenerating sensory and motor axons. Retinal ganglion cell axons were traced after 2 months. Dorsal root ganglia survived with their axons persisting throughout the graft. Comparable numbers of retinal ganglion cells regenerated axons into both dorsal root ganglia (1053+/-223) and conventional grafts (1323+/-881; P>0.05). The results indicate that an intact sensory environment supports central axon regeneration. PMID:16407770

  5. The Unfolded Protein Response in Retinal Vascular Diseases: Implications and Therapeutic Potential Beyond Protein Folding

    PubMed Central

    Zhang, Sarah X.; Ma, Jacey H.; Bhatta, Maulasri; Fliesler, Steven J.; Wang, Joshua J.

    2015-01-01

    Angiogenesis is a complex, step-wise process of new vessel formation that is involved in both normal embryonic development as well as postnatal pathological processes, such as cancer, cardiovascular disease, and diabetes. Aberrant blood vessel growth, also known as neovascularization, in the retina and the choroid is a major cause of vision loss in severe eye diseases, such as diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and central and branch retinal vein occlusion. Yet, retinal neovascularization is causally and dynamically associated with vasodegeneration, ischemia, and vascular remodeling in retinal tissues. Understanding the mechanisms of retinal neovascularization is an urgent unmet need for developing new treatments for these devastating diseases. Accumulating evidence suggests a vital role for the unfolded protein response (UPR) in regulation of angiogenesis, in part through coordinating the secretion of pro-angiogenic growth factors, such as VEGF, and modulating endothelial cell survival and activity. Herein, we summarize current research in the context of endoplasmic reticulum (ER) stress and UPR signaling in retinal angiogenesis and vascular remodeling, highlighting potential implications of targeting these stress response pathways in the prevention and treatment of retinal vascular diseases that result in visual deficits and blindness. PMID:25529848

  6. Changes in ganglion cell physiology during retinal degeneration influence excitability by prosthetic electrodes

    NASA Astrophysics Data System (ADS)

    Cho, Alice; Ratliff, Charles; Sampath, Alapakkam; Weiland, James

    2016-04-01

    Objective. Here we investigate ganglion cell physiology in healthy and degenerating retina to test its influence on threshold to electrical stimulation. Approach. Age-related Macular Degeneration and Retinitis Pigmentosa cause blindness via outer retinal degeneration. Inner retinal pathways that transmit visual information to the central brain remain intact, so direct electrical stimulation from prosthetic devices offers the possibility for visual restoration. Since inner retinal physiology changes during degeneration, we characterize physiological properties and responses to electrical stimulation in retinal ganglion cells (RGCs) of both wild type mice and the rd10 mouse model of retinal degeneration. Main results. Our aggregate results support previous observations that elevated thresholds characterize diseased retinas. However, a physiology-driven classification scheme reveals distinct sub-populations of ganglion cells with thresholds either normal or strongly elevated compared to wild-type. When these populations are combined, only a weakly elevated threshold with large variance is observed. The cells with normal threshold are more depolarized at rest and exhibit periodic oscillations. Significance. During degeneration, physiological changes in RGCs affect the threshold stimulation currents required to evoke action potentials.

  7. Retinal and post-retinal contributions to the quantum efficiency of the human eye revealed by electrical neuroimaging

    PubMed Central

    Manasseh, Gibran; de Balthasar, Chloe; Sanguinetti, Bruno; Pomarico, Enrico; Gisin, Nicolas; de Peralta, Rolando Grave; Andino, Sara L. Gonzalez

    2013-01-01

    The retina is one of the best known quantum detectors with rods able to reliably respond to single photons. However, estimates on the number of photons eliciting conscious perception, based on signal detection theory, are systematically above these values after discounting by retinal losses. One possibility is that there is a trade-off between the limited motor resources available to living systems and the excellent reliability of the visual photoreceptors. On this view, the limits to sensory thresholds are not set by the individual reliability of the receptors within each sensory modality (as often assumed) but rather by the limited central processing and motor resources available to process the constant inflow of sensory information. To investigate this issue, we reproduced the classical experiment from Hetch aimed to determine the sensory threshold in human vision. We combined a careful physical control of the stimulus parameters with high temporal/spatial resolution recordings of EEG signals and behavioral variables over a relatively large sample of subjects (12). Contrarily to the idea that the limits to visual sensitivity are fully set by the statistical fluctuations in photon absorption on retinal photoreceptors we observed that the state of ongoing neural oscillations before any photon impinges the retina helps to determine if the responses of photoreceptors have access to central conscious processing. Our results suggest that motivational and attentional off-retinal mechanisms play a major role in reducing the QE efficiency of the human visual system when compared to the efficiency of isolated retinal photoreceptors. Yet, this mechanism might subserve adaptive behavior by enhancing the overall multisensory efficiency of the whole system composed by diverse reliable sensory modalities. PMID:24302913

  8. Retinal and post-retinal contributions to the quantum efficiency of the human eye revealed by electrical neuroimaging.

    PubMed

    Manasseh, Gibran; de Balthasar, Chloe; Sanguinetti, Bruno; Pomarico, Enrico; Gisin, Nicolas; de Peralta, Rolando Grave; Andino, Sara L Gonzalez

    2013-01-01

    The retina is one of the best known quantum detectors with rods able to reliably respond to single photons. However, estimates on the number of photons eliciting conscious perception, based on signal detection theory, are systematically above these values after discounting by retinal losses. One possibility is that there is a trade-off between the limited motor resources available to living systems and the excellent reliability of the visual photoreceptors. On this view, the limits to sensory thresholds are not set by the individual reliability of the receptors within each sensory modality (as often assumed) but rather by the limited central processing and motor resources available to process the constant inflow of sensory information. To investigate this issue, we reproduced the classical experiment from Hetch aimed to determine the sensory threshold in human vision. We combined a careful physical control of the stimulus parameters with high temporal/spatial resolution recordings of EEG signals and behavioral variables over a relatively large sample of subjects (12). Contrarily to the idea that the limits to visual sensitivity are fully set by the statistical fluctuations in photon absorption on retinal photoreceptors we observed that the state of ongoing neural oscillations before any photon impinges the retina helps to determine if the responses of photoreceptors have access to central conscious processing. Our results suggest that motivational and attentional off-retinal mechanisms play a major role in reducing the QE efficiency of the human visual system when compared to the efficiency of isolated retinal photoreceptors. Yet, this mechanism might subserve adaptive behavior by enhancing the overall multisensory efficiency of the whole system composed by diverse reliable sensory modalities. PMID:24302913

  9. Choroidal thickness profile in Retinitis Pigmentosa – Correlation with outer retinal structures

    PubMed Central

    Chhablani, Jay; Jonnadula, Ganesh Babu; Srinivasa Rao, P.; Venkata, Amarnath; Jalali, Subhadra

    2015-01-01

    Purpose To compare the choroidal thickness (CT) of subjects with Retinitis Pigmentosa (RP) with age-matched healthy subjects and to correlate the visual acuity with retinal parameters including central macular thickness (CMT), inner segment/outer segment junction (IS/OS junction) integrity, external limiting membrane (ELM) integrity and choroidal thickness in subjects with RP. Methods Eighty-eight eyes (69 patients) with typical RP and 188 eyes of 104 healthy subjects were enrolled between September 2012 and January 2013. All subjects underwent a comprehensive ocular examination including choroidal imaging using enhanced depth imaging with spectral domain optical coherence tomography. Outcome measures were CT difference between RP and age-matched healthy subjects; and correlation of various factors such CMT, IS/OS junction integrity, ELM integrity, and CT with visual acuity. Results Among RP subjects, mean age was 31.39 ± 13.4 years with a mean BCVA of 0.99 ± 0.94 logMAR. Mean spherical equivalent was −0.6 ± 1.6D. Mean CMT was 148.48 ± 119 μm. Mean subfoveal CT was 296.9 ± 72 μm. Mean IS/OS and ELM integrity was 42.2 ± 46.6% and 43.75 ± 45.7%, respectively. The mean age was 40.0 ± 13.5 years with a mean spherical equivalent of 0.18 ± 0.6D for the normal age-matched healthy group. Mean subfoveal CT was 283.1 ± 47.8 μm. CT at various locations in patients of various ages in the RP group did not show any statistical significant difference (P = ≫0.05) in comparison with age-matched healthy subjects. On multivariate regression, ELM percentage integrity had the strongest association with best corrected visual acuity, followed by IS/OS junction percentage integrity. Subfoveal choroidal thickness had very weak correlation with visual acuity as well other retinal parameters. There was a significant difference in the outer retinal structure integrity (p = 0.002) and CMT (p = 0.02) between the eyes with good (⩾20/200) and

  10. Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis

    PubMed Central

    Singh, P K; Kumar, A

    2016-01-01

    Bacterial endophthalmitis, a vision-threatening complication of ocular surgery or trauma, is characterized by increased intraocular inflammation and retinal tissue damage. Although significant vision loss in endophthalmitis has been linked to retinal cell death, the underlying mechanisms of cell death remain elusive. In this study, using a mouse model of Staphylococcus aureus endophthalmitis and cultured human retinal Müller glia (MIO-M1 cell line), we demonstrate that S. aureus caused significant apoptotic cell death in the mouse retina and Müller glia, as evidenced by increased number of terminal dUTP nick end labeling and Annexin V and propidium iodide-positive cells. Immunohistochemistry and western blot studies revealed the reduction in mitochondrial membrane potential (JC-1 staining), release of cytochrome c into the cytosol, translocation of Bax to the mitochondria and the activation of caspase-9 and -3 in S. aureus-infected retina/retinal cells. In addition, the activation of PARP-1 and the release of apoptosis inducing factor from mitochondria was also observed in S. aureus-infected retinal cells. Inhibition studies using pan-caspase (Q-VD-OPH) and PARP-1 (DPQ) inhibitors showed significant reduction in S. aureus-induced retinal cell death both in vivo and in vitro. Together, our findings demonstrate that in bacterial endophthalmitis, retinal cells undergo apoptosis in the both caspase-dependent and independent manners, and mitochondria have a central role in this process. Hence, targeting the identified signaling pathways may provide the rationale to design therapeutic interventions to prevent bystander retinal tissue damage in bacterial endophthalmitis. PMID:27551524

  11. Mitochondria mediates caspase-dependent and independent retinal cell death in Staphylococcus aureus endophthalmitis.

    PubMed

    Singh, P K; Kumar, A

    2016-01-01

    Bacterial endophthalmitis, a vision-threatening complication of ocular surgery or trauma, is characterized by increased intraocular inflammation and retinal tissue damage. Although significant vision loss in endophthalmitis has been linked to retinal cell death, the underlying mechanisms of cell death remain elusive. In this study, using a mouse model of Staphylococcus aureus endophthalmitis and cultured human retinal Müller glia (MIO-M1 cell line), we demonstrate that S. aureus caused significant apoptotic cell death in the mouse retina and Müller glia, as evidenced by increased number of terminal dUTP nick end labeling and Annexin V and propidium iodide-positive cells. Immunohistochemistry and western blot studies revealed the reduction in mitochondrial membrane potential (JC-1 staining), release of cytochrome c into the cytosol, translocation of Bax to the mitochondria and the activation of caspase-9 and -3 in S. aureus-infected retina/retinal cells. In addition, the activation of PARP-1 and the release of apoptosis inducing factor from mitochondria was also observed in S. aureus-infected retinal cells. Inhibition studies using pan-caspase (Q-VD-OPH) and PARP-1 (DPQ) inhibitors showed significant reduction in S. aureus-induced retinal cell death both in vivo and in vitro. Together, our findings demonstrate that in bacterial endophthalmitis, retinal cells undergo apoptosis in the both caspase-dependent and independent manners, and mitochondria have a central role in this process. Hence, targeting the identified signaling pathways may provide the rationale to design therapeutic interventions to prevent bystander retinal tissue damage in bacterial endophthalmitis. PMID:27551524

  12. Role of retinal vascular endothelial cells in development of CMV retinitis.

    PubMed Central

    Rao, N A; Zhang, J; Ishimoto, S

    1998-01-01

    PURPOSE: Although cytomegalovirus (CMV) retinitis is known to occur in association with retinal microangiopathy in individuals with marked immunodeficiency, glial cells are believed to be the initial target cells in the development of retinitis. Moreover, it has been hypothesized that CMV gains access to the retinal glia because of altered vascular permeability. In an attempt to address the hypothesis, we studied 30 autopsy eyes of AIDS patients with systemic CMV infection, with or without clinically apparent CMV retinitis. METHODS: The autopsy eyes were processed in three ways. First, dual immunohistochemical studies were done by using anti-CMV antibodies for immediate early, early, and late antigens. The retinal cell types infected with the virus were then determined by using anti-GFAP, anti-VonWillebrand's factor, neuronal specific enolase, and leukocyte marker CD68. Second, selected eyes were processed for in situ hybridization with DNA probe specific to CMV. Third, an eye with clinically apparent CMV retinitis was submitted for electron microscopic examination. RESULTS: At the site of retinal necrosis in those eyes with a clinical diagnosis of CMV retinitis, the immunohistochemical, in situ hybridization, and ultrastructural examinations revealed that CMV was present primarily in the Müller cells and in perivascular glial cells. Adjacent to these infected cells, focal areas of positive staining for CMV antigen were seen in the glial cells, neuronal cells, and retinal pigment epithelial cells. At these sites most of the retinal capillaries were devoid of endothelial cells. Few vessels located at the advancing margin of retinal necrosis showed the presence of viral proteins in the endothelial cells. CONCLUSIONS: The present results indicate that retinal vascular endothelial cells could be the initial target in the development of viral retinitis, with subsequent spread of the infection to perivascular glia, Müller cells, and other retinal cells, including the

  13. Mechanical Dissociation of Retinal Neurons with Vibration

    NASA Astrophysics Data System (ADS)

    Motomura, Tamami; Hayashida, Yuki; Murayama, Nobuki

    The neuromorphic device, which implements the functions of biological neural circuits by means of VLSI technology, has been collecting much attention in the engineering fields in the last decade. Concurrently, progress in neuroscience research has revealed the nonlinear computation in single neuron levels, suggesting that individual neurons are not merely the circuit elements but computational units. Thus, elucidating the properties of neuronal signal processing is thought to be an essential step for developing the next generation of neuromorphic devices. In the present study, we developed a method for dissociating single neurons from specific sublayers of mammalian retinas with using no proteolytic enzymes but rather combining tissue incubation in a low-Ca2+ medium and the vibro-dissociation technique developed for the slices of brains and spinal cords previously. Our method took shorter time of the procedure, and required less elaborated skill, than the conventional enzymatic method did; nevertheless it yielded enough number of the cells available for acute electrophysiological experiments. The isolated retinal neurons were useful for measuring the nonlinear membrane conductances as well as the spike firing properties under the perforated-patch whole-cell configuration. These neurons also enabled us to examine the effects of proteolytic enzymes on the membrane excitability in those cells.

  14. Gene Therapy for Retinal Diseases

    PubMed Central

    Samiy, Nasrollah

    2014-01-01

    Gene therapy has a growing research potential particularly in the field of ophthalmic and retinal diseases owing to three main characteristics of the eye; accessibility in terms of injections and surgical interventions, its immune-privileged status facilitating the accommodation to the antigenicity of a viral vector, and tight blood-ocular barriers which save other organs from unwanted contamination. Gene therapy has tremendous potential for different ocular diseases. In fact, the perspective of gene therapy in the field of eye research does not confine to exclusive monogenic ophthalmic problems and it has the potential to include gene based pharmacotherapies for non-monogenic problems such as age related macular disease and diabetic retinopathy. The present article has focused on how gene transfer into the eye has been developed and used to treat retinal disorders with no available therapy at present. PMID:25709778

  15. Retinitis pigmentosa in southern Africa.

    PubMed

    Greenberg, J; Bartmann, L; Ramesar, R; Beighton, P

    1993-11-01

    Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders which are a common cause of genetic blindness. The relative frequencies of the different forms of RP in South Africa, as determined from the register at the DNA banking centre for RP at the Department of Human Genetics, University of Cape Town, are presented and discussed. Of the 125 families analysed, 29 (23%) showed autosomal dominant, 33 (27%) autosomal recessive and 3 (3%) X-linked inheritance. In 10 families the pedigree data were insufficient to allow accurate genetic subtyping and a further 50 patients were sporadic without a family history of RP or other syndromic features which would allow categorization. PMID:8313621

  16. Retinal vein occlusion: current treatment.

    PubMed

    Lattanzio, Rosangela; Torres Gimeno, Ana; Battaglia Parodi, Maurizio; Bandello, Francesco

    2011-01-01

    Retinal vein occlusion (RVO) is a pathology noted for more than 150 years. Although a lot has been written on the matter, it is still a frequent condition with multifactorial etiopathogenesis with many unclear aspects. The RVO pathogenesis has varied systemic and local implications that make it difficult to elaborate treatment guidelines. The management of the patient with RVO is very complex and a multidisciplinary approach is required in order to identify and correct the associated risk factors. Laser therapy remains the gold standard in RVO, but only modest functional improvement has been shown in branch retinal occlusion forms. Multicenter studies of intravitreal drugs present them as an option to combine with laser. Anti-vascular endothelial growth factor, corticosteroids and sustained-release implants are the future weapons to stop disease progression and get a better visual outcome. Consequently, it is useful to clarify some aspects of the pathology that allow a better patient management. PMID:20938213

  17. Operational challenges of retinal prostheses.

    PubMed

    Schmid, Erich W; Fink, Wolfgang; Wilke, Robert

    2014-12-01

    Two computational models for research on retinal implants are presented. In the first model, the electric field produced by a multi-electrode array in a uniform retina is calculated. It is shown how cross talk of activated electrodes and the resulting bunching of field lines in monopole and dipole activation prevent high resolution imaging with retinal implants. Furthermore, it is demonstrated how sequential stimulation and multipolar stimulation may overcome this limitation. In the second model a target volume, i.e., a probe cylinder approximating a bipolar cell, in the retina is chosen, and the passive Heaviside cable equation is solved inside this target volume to calculate the depolarization of the cell membrane. The depolarization as a function of time indicates that shorter signals stimulate better as long as the current does not change sign during stimulation of the retina, i.e., mono-phasic stimulation. Both computational models are equally applicable to epiretinal, subretinal, and suprachoroidal vision implants. PMID:25443535

  18. Retinal microvascular caliber and chronic kidney disease in an Asian population.

    PubMed

    Sabanayagam, Charumathi; Shankar, Anoop; Koh, David; Chia, Kee Seng; Saw, Seang Mei; Lim, Su Chi; Tai, E Shyong; Wong, Tien Yin

    2009-03-01

    Retinal arteriolar narrowing is a marker of microvascular damage from elevated blood pressure. Between August 2004 and June 2006, the authors examined the association between retinal vascular diameter and chronic kidney disease in a population-based cohort of 3,280 community-dwelling adults of Malay ethnicity aged 40-80 years living in Singapore. Chronic kidney disease was defined as 1) an estimated glomerular filtration rate (eGFR) of <60 mL/minute/1.73 m(2) from serum creatinine or 2) the presence of micro/macroalbuminuria defined as urinary albumin:creatinine ratios of > or = 17 mg/g for men and > or = 25 mg/g for women. Retinal arteriolar and venular diameters were measured and summarized as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Individuals with reduced CRAE were more likely to have chronic kidney disease than those with increased CRAE. After controlling for age, gender, education, smoking, diabetes, hypertension, body mass index, and total and high density lipoprotein cholesterol, the authors found the odds ratio comparing the smallest with the largest CRAE quartile to be 1.42 (95% confidence interval: 1.03, 1.96; P(trend) = 0.02) for eGFR of <60 mL/minute/1.73 m(2) and 1.80 (95% confidence interval: 1.11, 2.91; P(trend) = 0.01) for micro/macroalbuminuria. Retinopathy was also found to be positively associated with both eGFR and micro/macroalbuminuria. Retinal venular diameter was not associated with chronic kidney disease. These data suggest that retinal arteriolar narrowing is associated with chronic kidney disease, independent of diabetes and hypertension. PMID:19092170

  19. Acquired retinal folds in the cat.

    PubMed

    MacMillan, A D

    1976-06-01

    Retinal folds were found in 5 cats. The apparent cause of the folding was varied: in 1 cat the folds appeared after a localized retinal detachment; in 2 cats the condition accompanied other intraocular abnormalities associated with feline infectious peritonitis; 1 cat had active keratitis, and the retinal changes were thought to have been injury related; and 1 cat, bilaterally affected, had chronic glomerulonephritis. PMID:945253

  20. Angiographic results of retinal-retinal anastomosis and retinal-choroidal anastomosis after treatments in eyes with retinal angiomatous proliferation

    PubMed Central

    Saito, Masaaki; Iida, Tomohiro; Kano, Mariko; Itagaki, Kanako

    2012-01-01

    Background The purpose of this study was to evaluate the angiographic results of retinal-retinal anastomosis (RRA) and retinal-choroidal anastomosis (RCA) for eyes with retinal angiomatous proliferation (RAP) after treatment with intravitreal bevacizumab injections as monotherapy or intravitreal bevacizumab combined with photodynamic therapy. Methods In this interventional, consecutive case series, we retrospectively reviewed five naïve eyes from four patients (mean age 80 years) treated with three consecutive monthly intravitreal bevacizumab (1.25 mg/0.05 mL) injections as initial treatment, and followed up for at least 3 months. In cases with over 3 months of follow-up and having recurrence of RAP or leakage by fluorescein angiography, retreatment was performed with a single intravitreal bevacizumab injection and photodynamic therapy. Results Indocyanine green angiography showed RRA in three eyes with subretinal neovascularization and RCA in two eyes with choroidal neovascularization at baseline. At 3 months after baseline (month 3), neither the RRA nor RCA was occluded in any eye on indocyanine green angiography. Retreatment with intravitreal bevacizumab plus photodynamic therapy was performed in three eyes at months 3 (persistent leakage on fluorescein angiography), 6, and 7 (recurrence of RAP lesion), which achieved obvious occlusion of the RRA and RCA. Mean best-corrected visual acuity improved from 0.13 to 0.21 at month 3 (P = 0.066). No complications or systemic adverse events were noted. Conclusion Although intravitreal bevacizumab for RAP was effective in improving visual acuity during short-term follow-up, intravitreal bevacizumab could not achieve complete occlusion of RRA and RCA, which could lead to recurrence of a RAP lesion and exudation. Retreatment with intravitreal bevacizumab plus photodynamic therapy ultimately achieved complete occlusion of the RRA and RCA. PMID:22969283

  1. Double Dissociation of Monoacylglycerol Lipase Inhibition and CB1 Antagonism in the Central Amygdala, Basolateral Amygdala, and the Interoceptive Insular Cortex on the Affective Properties of Acute Naloxone-Precipitated Morphine Withdrawal in Rats.

    PubMed

    Wills, Kiri L; Petrie, Gavin N; Millett, Geneva; Limebeer, Cheryl L; Rock, Erin M; Niphakis, Micah J; Cravatt, Benjamin F; Parker, Linda A

    2016-06-01

    Both CB1 receptor antagonism and agonism, in particular by 2-arachidonyl glycerol (2-AG), have been shown to reduce somatic symptoms of morphine withdrawal (MWD). Here we evaluated the effects of both systemic pretreatment with the monoacylglycerol lipase (MAGL) inhibitor MJN110 (which selectively elevates 2-AG) and central administration of both MJN110 and the CB1 antagonist (AM251) on the affective properties of MWD. Acute MWD induced place aversion occurs when naloxone is administered 24 h following a single exposure to a high dose of morphine. Systemic pretreatment with the MAGL inhibitor, MJN110, prevented the aversive effects of acute MWD by a CB1 receptor-dependent mechanism. Furthermore, in a double dissociation, AM251 infusions into the central amygdala, but MJN110 infusions into the basolateral amygdala, interfered with the naloxone-precipitated MWD induced place aversion. As well, MJN110, but not AM251, infusions into the interoceptive insular cortex (a region known to be activated in acute MWD) also prevented the establishment of the place aversion by a CB1 mechanism of action. These findings reveal the respective sites of action of systemically administered MJN110 and AM251 in regulating the aversive effects of MWD. PMID:26647976

  2. Hypoxia-Induced Retinal Neovascularization in Zebrafish Embryos: A Potential Model of Retinopathy of Prematurity

    PubMed Central

    Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

    2015-01-01

    Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2–4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression. PMID:25978439

  3. Hypoxia-induced retinal neovascularization in zebrafish embryos: a potential model of retinopathy of prematurity.

    PubMed

    Wu, Yu-Ching; Chang, Chao-Yuan; Kao, Alex; Hsi, Brian; Lee, Shwu-Huey; Chen, Yau-Hung; Wang, I-Jong

    2015-01-01

    Retinopathy of prematurity, formerly known as a retrolental fibroplasia, is a leading cause of infantile blindness worldwide. Retinopathy of prematurity is caused by the failure of central retinal vessels to reach the retinal periphery, creating a nonperfused peripheral retina, resulting in retinal hypoxia, neovascularization, vitreous hemorrhage, vitreoretinal fibrosis, and loss of vision. We established a potential retinopathy of prematurity model by using a green fluorescent vascular endothelium zebrafish transgenic line treated with cobalt chloride (a hypoxia-inducing agent), followed by GS4012 (a vascular endothelial growth factor inducer) at 24 hours postfertilization, and observed that the number of vascular branches and sprouts significantly increased in the central retinal vascular trunks 2-4 days after treatment. We created an angiography method by using tetramethylrhodamine dextran, which exhibited severe vascular leakage through the vessel wall into the surrounding retinal tissues. The quantification of mRNA extracted from the heads of the larvae by using real-time quantitative polymerase chain reaction revealed a twofold increase in vegfaa and vegfr2 expression compared with the control group, indicating increased vascular endothelial growth factor signaling in the hypoxic condition. In addition, we demonstrated that the hypoxic insult could be effectively rescued by several antivascular endothelial growth factor agents such as SU5416, bevacizumab, and ranibizumab. In conclusion, we provide a simple, highly reproducible, and clinically relevant retinopathy of prematurity model based on zebrafish embryos; this model may serve as a useful platform for clarifying the mechanisms of human retinopathy of prematurity and its progression. PMID:25978439

  4. Measurement of Retinal Sensitivity on Tablet Devices in Age-Related Macular Degeneration

    PubMed Central

    Wu, Zhichao; Guymer, Robyn H.; Jung, Chang J.; Goh, Jonathan K.; Ayton, Lauren N.; Luu, Chi D.; Lawson, David J.; Turpin, Andrew; McKendrick, Allison M.

    2015-01-01

    Purpose: We compared measurements of central retinal sensitivity on a portable, low-cost tablet device to the established method of microperimetry in age-related macular degeneration (AMD). Methods: A customized test designed to measure central retinal sensitivity (within the central 1° radius) on a tablet device was developed using an open-source platform called PsyPad. A total of 30 participants with AMD were included in this study, and all participants performed a practice test on PsyPad, followed by four tests of one eye and one test of the other eye. Participants then underwent standardized microperimetry examinations in both eyes. Results: The average test duration on PsyPad was 53.9 ± 7.5 seconds, and no significant learning effect was observed over the examinations performed (P = 1.000). The coefficient of repeatability of central retinal sensitivity between the first two examinations on PsyPad was ±1.76 dB. The mean central retinal sensitivity was not significantly different between PsyPad (25.7 ± 0.4 dB) and microperimetry (26.1 ± 0.4 dB, P = 0.094), and the 95% limits of agreement between the two measures were between −4.12 and 4.92 dB. Conclusions: The measurements of central retinal sensitivity can be performed effectively using a tablet device, displaying reasonably good agreement with those obtained using the established method of microperimetry. Translational Relevance: These findings highlight the potential of tablet devices as low-cost and portable tools for developing and performing visual function measures that can be easily and widely implemented. PMID:26175959

  5. The peptidomimetic Vasotide targets two retinal VEGF receptors and reduces pathological angiogenesis in murine and nonhuman primate models of retinal disease

    PubMed Central

    Sidman, Richard L.; Li, Jianxue; Lawrence, Matthew; Hu, Wenzheng; Musso, Gary F.; Giordano, Ricardo J.; Cardó-Vila, Marina; Pasqualini, Renata; Arap, Wadih

    2016-01-01

    Blood vessel growth from preexisting vessels (angiogenesis) underlies many severe diseases including major blinding retinal diseases such as retinopathy of prematurity (ROP) and aged macular degeneration (AMD). This observation has driven development of antibody inhibitors that block a central factor in AMD, named vascular endothelial growth factor (VEGF), from binding to its receptors VEGFR-1 and VEGFR-2. However, some patients are insensitive to current anti-VEGF drugs or develop resistance, and the required repeated intravitreal injection of these large molecules is costly and clinically problematic. Here, we have evaluated a small cyclic retro-inverted peptidomimetic, D(Cys-Leu-Pro-Arg-Cys), abbreviated as D(CLPRC), and hereafter named Vasotide, that inhibits retinal angiogenesis by binding selectively to the VEGF receptors, VEGFR-1 and Neuropilin-1 (NRP-1). Delivery of Vasotide in eye drops or via intraperitoneal injection in a laser-induced monkey model of human wet AMD, a mouse genetic knockout model of the AMD subtype called retinal angiomatous proliferation (RAP), and a mouse oxygen-induced model of retinopathy of prematurity (ROP) markedly decreased retinal angiogenesis in all three animal models. This prototype drug candidate is a promising new dual receptor inhibitor of the VEGF ligand with potential for translation into safer, less invasive applications to combat pathological angiogenesis in retinal disorders. PMID:26468327

  6. Retinal Cell Degeneration in Animal Models

    PubMed Central

    Niwa, Masayuki; Aoki, Hitomi; Hirata, Akihiro; Tomita, Hiroyuki; Green, Paul G.; Hara, Akira

    2016-01-01

    The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-d-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage. PMID:26784179

  7. Retinal Effects Of Blue Light Exposure

    NASA Astrophysics Data System (ADS)

    Ham, William T.; Mueller, Harold A.; Ruffolo, J. J.

    1980-10-01

    Recent research has shown that blue light exposure is an important factor in certain types of retinal injury. The mammalian ocular media transmits the spectral band 400-1400 nm to the retina. The short wavelengths (400-550 nm) produce a photochemical or actinic type of damage, while the longer wavelengths (550-1400 nm) produce thermal damage. Distinction between the two types of retinal damage are discussed briefly and the importance of the blue light effect for solar retinitis and eclipse blindness is emphasized. The significance of blue light retinal injury is summarized for various environmental and occupational exposures.

  8. Retinal Macroglial Responses in Health and Disease

    PubMed Central

    de Hoz, Rosa; Rojas, Blanca; Ramírez, Ana I.; Salazar, Juan J.; Gallego, Beatriz I.; Triviño, Alberto; Ramírez, José M.

    2016-01-01

    Due to their permanent and close proximity to neurons, glial cells perform essential tasks for the normal physiology of the retina. Astrocytes and Müller cells (retinal macroglia) provide physical support to neurons and supplement them with several metabolites and growth factors. Macroglia are involved in maintaining the homeostasis of extracellular ions and neurotransmitters, are essential for information processing in neural circuits, participate in retinal glucose metabolism and in removing metabolic waste products, regulate local blood flow, induce the blood-retinal barrier (BRB), play fundamental roles in local immune response, and protect neurons from oxidative damage. In response to polyetiological insults, glia cells react with a process called reactive gliosis, seeking to maintain retinal homeostasis. When malfunctioning, macroglial cells can become primary pathogenic elements. A reactive gliosis has been described in different retinal pathologies, including age-related macular degeneration (AMD), diabetes, glaucoma, retinal detachment, or retinitis pigmentosa. A better understanding of the dual, neuroprotective, or cytotoxic effect of macroglial involvement in retinal pathologies would help in treating the physiopathology of these diseases. The extensive participation of the macroglia in retinal diseases points to these cells as innovative targets for new drug therapies. PMID:27294114

  9. Retinal detachment associated with atopic dermatitis.

    PubMed Central

    Takahashi, M; Suzuma, K; Inaba, I; Ogura, Y; Yoneda, K; Okamoto, H

    1996-01-01

    BACKGROUND: Retinal detachment associated with atopic dermatitis, one of the most common forms of dermatitis in Japan, has markedly increased in Japan in the past 10 years. To clarify pathogenic mechanisms of retinal detachment in such cases, we retrospectively studied clinical characteristics of retinal detachment associated with atopic dermatitis. METHODS: We examined the records of 80 patients (89 eyes) who had retinal detachment associated with atopic dermatitis. The patients were classified into three groups according to lens status: group A, eyes with clear lenses (40 eyes); group B, eyes with cataract (38 eyes), and group C, aphakic or pseudophakic eyes (11 eyes). RESULTS: No significant differences were noted in the ratio of males to females, age distribution, refractive error, or characteristic of retinal detachment among the three groups. The types of retinal breaks, however, were different in eyes with and without lens changes. While atrophic holes were dominant in group A, retinal dialysis was mainly seen in groups B and C. CONCLUSION: These findings suggested that anterior vitreoretinal traction may play an important role in the pathogenesis of retinal breaks in eyes with atopic cataract and that the same pathological process may affect the formation of cataract and tractional retinal breaks in patients with atopic dermatitis. PMID:8664234

  10. Polymerase chain reaction analysis of aqueous humour samples in necrotising retinitis

    PubMed Central

    Tran, T H C; Rozenberg, F; Cassoux, N; Rao, N A; LeHoang, P; Bodaghi, B

    2003-01-01

    Aim: To evaluate the diagnostic value of polymerase chain reaction (PCR) performed on aqueous humour for the detection of viral DNA in patients with necrotising herpetic retinitis. Methods: The clinical features and laboratory results of 22 patients (29 eyes) presenting with necrotising herpetic retinitis between March 1999 and June 2001 were reviewed retrospectively. Aqueous humour was obtained after anterior chamber paracentesis and PCR was performed in all cases. Results: Viral DNA was detected in the aqueous humour of 19 patients (86.4%). Epstein-Barr virus (EBV) seroconversion was evidenced in one additional patient. In the acute retinal necrosis (ARN) group (n = 19), varicella zoster virus (VZV) DNA was identified in six patients, herpes simplex virus 1 (HSV-1) DNA in two patients, herpes simplex virus 2 (HSV-2) DNA in four patients, and cytomegalovirus (CMV) genome in four patients. In the progressive outer retinal necrosis (PORN) group (n = 3), VZV DNA was detected in all patients. No sample was positive for more than one virus. Conclusions: PCR analysis of aqueous humour in patients with clinical features of necrotising viral retinitis can provide specific aetiological orientation and the method appears to be safe and highly sensitive. PMID:12488268

  11. Re-evaluating the treatment of acute optic neuritis

    PubMed Central

    Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

    2015-01-01

    Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis. Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite ‘normal’ (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury. In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration. In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. PMID:25355373

  12. Re-evaluating the treatment of acute optic neuritis.

    PubMed

    Bennett, Jeffrey L; Nickerson, Molly; Costello, Fiona; Sergott, Robert C; Calkwood, Jonathan C; Galetta, Steven L; Balcer, Laura J; Markowitz, Clyde E; Vartanian, Timothy; Morrow, Mark; Moster, Mark L; Taylor, Andrew W; Pace, Thaddeus W W; Frohman, Teresa; Frohman, Elliot M

    2015-07-01

    Clinical case reports and prospective trials have demonstrated a reproducible benefit of hypothalamic-pituitary-adrenal (HPA) axis modulation on the rate of recovery from acute inflammatory central nervous system (CNS) demyelination. As a result, corticosteroid preparations and adrenocorticotrophic hormones are the current mainstays of therapy for the treatment of acute optic neuritis (AON) and acute demyelination in multiple sclerosis.Despite facilitating the pace of recovery, HPA axis modulation and corticosteroids have failed to demonstrate long-term benefit on functional recovery. After AON, patients frequently report visual problems, motion perception difficulties and abnormal depth perception despite 'normal' (20/20) vision. In light of this disparity, the efficacy of these and other therapies for acute demyelination require re-evaluation using modern, high-precision paraclinical tools capable of monitoring tissue injury.In no arena is this more amenable than AON, where a new array of tools in retinal imaging and electrophysiology has advanced our ability to measure the anatomic and functional consequences of optic nerve injury. As a result, AON provides a unique clinical model for evaluating the treatment response of the derivative elements of acute inflammatory CNS injury: demyelination, axonal injury and neuronal degeneration.In this article, we examine current thinking on the mechanisms of immune injury in AON, discuss novel technologies for the assessment of optic nerve structure and function, and assess current and future treatment modalities. The primary aim is to develop a framework for rigorously evaluating interventions in AON and to assess their ability to preserve tissue architecture, re-establish normal physiology and restore optimal neurological function. PMID:25355373

  13. Retinal pigment epithelium transplantation: concepts, challenges, and future prospects

    PubMed Central

    Alexander, P; Thomson, H A J; Luff, A J; Lotery, A J

    2015-01-01

    The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD. PMID:26043704

  14. Retinal pigment epithelium transplantation: concepts, challenges, and future prospects.

    PubMed

    Alexander, P; Thomson, H A J; Luff, A J; Lotery, A J

    2015-08-01

    The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD. PMID:26043704

  15. Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma

    PubMed Central

    Madeira, Maria H.; Ortin-Martinez, Arturo; Nadal-Nícolas, Francisco; Ambrósio, António F.; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Santiago, Ana Raquel

    2016-01-01

    Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma. PMID:27270337

  16. Caffeine administration prevents retinal neuroinflammation and loss of retinal ganglion cells in an animal model of glaucoma.

    PubMed

    Madeira, Maria H; Ortin-Martinez, Arturo; Nadal-Nícolas, Francisco; Ambrósio, António F; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Santiago, Ana Raquel

    2016-01-01

    Glaucoma is the second leading cause of blindness worldwide, being characterized by progressive optic nerve damage and loss of retinal ganglion cells (RGCs), accompanied by increased inflammatory response involving retinal microglial cells. The etiology of glaucoma is still unknown, and despite elevated intraocular pressure (IOP) being a major risk factor, the exact mechanisms responsible for RGC degeneration remain unknown. Caffeine, which is an antagonist of adenosine receptors, is the most widely consumed psychoactive drug in the world. Several evidences suggest that caffeine can attenuate the neuroinflammatory responses and afford protection upon central nervous system (CNS) injury. We took advantage of a well characterized animal model of glaucoma to investigate whether caffeine administration controls neuroinflammation and elicits neuroprotection. Caffeine or water were administered ad libitum and ocular hypertension (OHT) was induced by laser photocoagulation of the limbal veins in Sprague Dawley rats. Herein, we show that caffeine is able to partially decrease the IOP in ocular hypertensive animals. More importantly, we found that drinking caffeine prevented retinal microglia-mediated neuroinflammatory response and attenuated the loss of RGCs in animals with ocular hypertension (OHT). This study opens the possibility that caffeine or adenosine receptor antagonists might be a therapeutic option to manage RGC loss in glaucoma. PMID:27270337

  17. Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions

    PubMed Central

    Trucco, E; Cameron, J R; Dhillon, B; Houston, J G; van Beek, E J R

    2014-01-01

    The black void behind the pupil was optically impenetrable before the invention of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal imaging and image processing, especially over the past decade, have opened a route to another unexplored landscape, the retinal neurovascular architecture and the retinal ganglion pathways linking to the central nervous system beyond. Exploiting these research opportunities requires multidisciplinary teams to explore the interface sitting at the border between ophthalmology, neurology and computing science. It is from the detail and depth of retinal phenotyping that novel metrics and candidate biomarkers are likely to emerge. Confirmation that in vivo retinal neurovascular measures are predictive of microvascular change in the brain and other organs is likely to be a major area of research activity over the next decade. Unlocking this hidden potential within the retina requires integration of structural and functional data sets, that is, multimodal mapping and longitudinal studies spanning the natural history of the disease process. And with further advances in imaging, it is likely that this area of retinal research will remain active and clinically relevant for many years to come. Accordingly, this review looks at state-of-the-art retinal imaging and its application to diagnosis, characterization and prognosis of chronic illness or long-term conditions. PMID:24936979

  18. Retinal imaging as a source of biomarkers for diagnosis, characterization and prognosis of chronic illness or long-term conditions.

    PubMed

    MacGillivray, T J; Trucco, E; Cameron, J R; Dhillon, B; Houston, J G; van Beek, E J R

    2014-08-01

    The black void behind the pupil was optically impenetrable before the invention of the ophthalmoscope by von Helmholtz over 150 years ago. Advances in retinal imaging and image processing, especially over the past decade, have opened a route to another unexplored landscape, the retinal neurovascular architecture and the retinal ganglion pathways linking to the central nervous system beyond. Exploiting these research opportunities requires multidisciplinary teams to explore the interface sitting at the border between ophthalmology, neurology and computing science. It is from the detail and depth of retinal phenotyping that novel metrics and candidate biomarkers are likely to emerge. Confirmation that in vivo retinal neurovascular measures are predictive of microvascular change in the brain and other organs is likely to be a major area of research activity over the next decade. Unlocking this hidden potential within the retina requires integration of structural and functional data sets, that is, multimodal mapping and longitudinal studies spanning the natural history of the disease process. And with further advances in imaging, it is likely that this area of retinal research will remain active and clinically relevant for many years to come. Accordingly, this review looks at state-of-the-art retinal imaging and its application to diagnosis, characterization and prognosis of chronic illness or long-term conditions. PMID:24936979

  19. Hard Retinal exudates and visual loss due to papilledema

    SciTech Connect

    Rush, J.A.

    1982-02-01

    Bilateral papilledema developed in a patient with a cystic, grade 3 astrocytoma of the right frontal lobe. Despite successful neurosurgical treatment, /sup 60/Co radiotherapy, and oral corticosteroid therapy, progressive visual loss occurred. At examination one year later, visual activity was 20/200 and 20/70, and extensive lipid exudates in the peripapillary retina and central macula of each eye were noted. Retinal lipid exudates rarely complicate the course of surviving patients who had papilledema from intracranial tumor; physicians involved in the multispecialty care of such patients should be aware of the possible ocular residuals of persistent papilledema in an otherwise successfully treated patient.

  20. Tri-functional cannula for retinal endovascular surgery

    DOEpatents

    Weiss, Jonathan D.

    2010-07-27

    A tri-functional cannula combines the functions of tissue Plasminogen Activator (tPA) solution delivery, illumination and venous pressure measurement. The cannula utilizes a tapered hollow-core optical fiber having an inlet for tPA solution, an attached fiber optic splitter configured to receive illumination light from an optical source such and a LED. A window in the cannula transmits the light to and from a central retinal vein. The return light is coupled to an optical detector to measure the pressure within the vein and determine whether an occlusion has been removed.

  1. Retinal nerve fiber layer thickness and retinal vessel calibers in children with thalassemia minor

    PubMed Central

    Acer, Semra; Balcı, Yasemin I; Pekel, Gökhan; Ongun, Tuğba T; Polat, Aziz; Çetin, Ebru N; Yağcı, Ramazan

    2016-01-01

    Objectives: Evaluation of the peripapillary retinal nerve fiber layer thickness, subfoveal choroidal thickness, and retinal vessel caliber measurements in children with thalassemia minor. Methods: In this cross-sectional and comparative study, 30 thalassemia minor patients and 36 controls were included. Heidelberg spectral domain optical coherence tomography was used for peripapillary retinal nerve fiber layer thickness, subfoveal choroidal thickness, and retinal vessel caliber measurements. Results: There was no statistically significant difference in retinal nerve fiber layer thickness and subfoveal choroidal thickness between the two groups (p > 0.05). There was no correlation between retinal nerve fiber layer thickness and hemoglobin values. Both the arterioral and venular calibers were higher in thalassemia minor group (p < 0.05). Conclusion: There is increased retinal arterioral and venular calibers in children with thalassemia minor compared with controls. PMID:27540484

  2. Retinal fundus imaging in mouse models of retinal diseases.

    PubMed

    Alex, Anne F; Heiduschka, Peter; Eter, Nicole

    2013-01-01

    The development of in vivo retinal fundus imaging in mice has opened a new research horizon, not only in ophthalmic research. The ability to monitor the dynamics of vascular and cellular changes in pathological conditions, such as neovascularization or degeneration, longitudinally without the need to sacrifice the mouse, permits longer observation periods in the same animal. With the application of the high-resolution confocal scanning laser ophthalmoscopy in experimental mouse models, access to a large spectrum of imaging modalities in vivo is provided. PMID:23150359

  3. Retinal dynamics underlie its switch from inverse agonist to agonist during rhodopsin activation.

    PubMed

    Struts, Andrey V; Salgado, Gilmar F J; Martínez-Mayorga, Karina; Brown, Michael F

    2011-03-01

    X-ray and magnetic resonance approaches, though central to studies of G protein-coupled receptor (GPCR)-mediated signaling, cannot address GPCR protein dynamics or plasticity. Here we show that solid-state (2)H NMR relaxation elucidates picosecond-to-nanosecond-timescale motions of the retinal ligand that influence larger-scale functional dynamics of rhodopsin in membranes. We propose a multiscale activation mechanism whereby retinal initiates collective helix fluctuations in the meta I-meta II equilibrium on the microsecond-to-millisecond timescale. PMID:21278756

  4. Argus II retinal prosthesis system: An update.

    PubMed

    Rachitskaya, Aleksandra V; Yuan, Alex

    2016-09-01

    This review focuses on a description of the Argus II retinal prosthesis system (Argus II; Second Sight Medical Products, Sylmar, CA) that was approved for humanitarian use by the FDA in 2013 in patients with retinitis pigmentosa with bare or no light perception vision. The article describes the components of Argus II, the studies on the implant, and future directions. PMID:26855177

  5. Fundus autofluorescence applications in retinal imaging.

    PubMed

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2015-05-01

    Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802

  6. Fundus autofluorescence applications in retinal imaging

    PubMed Central

    Gabai, Andrea; Veritti, Daniele; Lanzetta, Paolo

    2015-01-01

    Fundus autofluorescence (FAF) is a relatively new imaging technique that can be used to study retinal diseases. It provides information on retinal metabolism and health. Several different pathologies can be detected. Peculiar AF alterations can help the clinician to monitor disease progression and to better understand its pathogenesis. In the present article, we review FAF principles and clinical applications. PMID:26139802

  7. Retinal cholesterol emboli during diagnostic cardiac catheterization.

    PubMed

    Blanco, V R; Morís, C; Barriales, V; González, C

    2000-11-01

    Retinal embolism is a highly infrequent complication of cardiac catheterization of thrombotic, lipidic, and calcific etiology. We provide the first reported clinical case of retinal embolism caused by cholesterol crystal without systemic adverse effects as a severe complication of diagnostic cardiac catheterization. Cathet. Cardiovasc. Intervent. 51:323-325, 2000. PMID:11066118

  8. New mouse primary retinal degeneration (rd-3)

    SciTech Connect

    Chang, B.; Hawes, N.L.; Roderick, T.H. ); Heckenlively, J.R. )

    1993-04-01

    A new mouse retinal degeneration that appears to be an excellent candidate for modeling human retinitis pigmentosa is reported. In this degeneration, called rd-3, differentiation proceeds postnatally through 2 weeks, and photoreceptor degeneration starts by 3 weeks. The rod photoreceptor loss is essentially complete by 5 weeks, whereas remnant cone cells are seen through 7 weeks. This is the only mouse homozygous retinal degeneration reported to date in which photoreceptors are initially normal. Crosses with known mouse retinal degenerations rd, Rds, nr, and pcd are negative for retinal degeneration in offspring, and linkage analysis places rd-3 on mouse chromosome 1 at 10 [+-]2.5 cM distal to Akp-1. Homology mapping suggests that the homologous human locus should be on chromosome 1q. 32 refs., 3 figs., 3 tabs.

  9. Retinal pigment epithelium in incontinentia pigmenti.

    PubMed

    Mensheha-Manhart, O; Rodrigues, M M; Shields, J A; Shannon, G M; Mirabelli, R P

    1975-04-01

    An 18-month-old white girl with incontinentia pigmenti presented clinically with leukokoria of the right eye. B-scan ultrasound demonstrated a retrolental mass consistent with a detached retina. Histologic examination of the skin revealed changes compatible with the intermediate verrucous phase of the disease. Microscopic examination of the right eye showed retinal detachment and nodular proliferation of the retinal pigment epithelium. The nodules contained macrophages laden with melanin and lipofuscin. An unusually large amount of lipofuscin was present for a child of this age. The basic pigmentary abnormality may affect the retinal pigment epithelium, resulting in changes in the overlying neurosensory retina that may lead to the retinal dysplasia or retinal detachemnt often associated with this condition. PMID:1119517

  10. The cell stress machinery and retinal degeneration.

    PubMed

    Athanasiou, Dimitra; Aguilà, Monica; Bevilacqua, Dalila; Novoselov, Sergey S; Parfitt, David A; Cheetham, Michael E

    2013-06-27

    Retinal degenerations are a group of clinically and genetically heterogeneous disorders characterised by progressive loss of vision due to neurodegeneration. The retina is a highly specialised tissue with a unique architecture and maintaining homeostasis in all the different retinal cell types is crucial for healthy vision. The retina can be exposed to a variety of environmental insults and stress, including light-induced damage, oxidative stress and inherited mutations that can lead to protein misfolding. Within retinal cells there are different mechanisms to cope with disturbances in proteostasis, such as the heat shock response, the unfolded protein response and autophagy. In this review, we discuss the multiple responses of the retina to different types of stress involved in retinal degenerations, such as retinitis pigmentosa, age-related macular degeneration and glaucoma. Understanding the mechanisms that maintain and re-establish proteostasis in the retina is important for developing new therapeutic approaches to fight blindness. PMID:23684651

  11. Texton-based segmentation of retinal vessels.

    PubMed

    Adjeroh, Donald A; Kandaswamy, Umasankar; Odom, J Vernon

    2007-05-01

    With improvements in fundus imaging technology and the increasing use of digital images in screening and diagnosis, the issue of automated analysis of retinal images is gaining more serious attention. We consider the problem of retinal vessel segmentation, a key issue in automated analysis of digital fundus images. We propose a texture-based vessel segmentation algorithm based on the notion of textons. Using a weak statistical learning approach, we construct textons for retinal vasculature by designing filters that are specifically tuned to the structural and photometric properties of retinal vessels. We evaluate the performance of the proposed approach using a standard database of retinal images. On the DRIVE data set, the proposed method produced an average performance of 0.9568 specificity at 0.7346 sensitivity. This compares well with the best-published results on the data set 0.9773 specificity at 0.7194 sensitivity [Proc. SPIE5370, 648 (2004)]. PMID:17429484

  12. Texton-based segmentation of retinal vessels

    NASA Astrophysics Data System (ADS)

    Adjeroh, Donald A.; Kandaswamy, Umasankar; Odom, J. Vernon

    2007-05-01

    With improvements in fundus imaging technology and the increasing use of digital images in screening and diagnosis, the issue of automated analysis of retinal images is gaining more serious attention. We consider the problem of retinal vessel segmentation, a key issue in automated analysis of digital fundus images. We propose a texture-based vessel segmentation algorithm based on the notion of textons. Using a weak statistical learning approach, we construct textons for retinal vasculature by designing filters that are specifically tuned to the structural and photometric properties of retinal vessels. We evaluate the performance of the proposed approach using a standard database of retinal images. On the DRIVE data set, the proposed method produced an average performance of 0.9568 specificity at 0.7346 sensitivity. This compares well with the best-published results on the data set 0.9773 specificity at 0.7194 sensitivity [Proc. SPIE5370, 648 (2004)].

  13. Sildenafil alters retinal function in mouse carriers of retinitis pigmentosa.

    PubMed

    Nivison-Smith, Lisa; Zhu, Yuan; Whatham, Andrew; Bui, Bang V; Fletcher, Erica L; Acosta, Monica L; Kalloniatis, Michael

    2014-11-01

    Sildenafil, the active ingredient in Viagra, has been reported to cause transient visual disturbance from inhibition of phosphodiesterase 6 (PDE6), a key enzyme in the visual phototransduction pathway. This study investigated the effects of sildenafil on the rd1(+/-) mouse, a model for carriers of Retinitis Pigmentosa which exhibit normal vision but may have a lower threshold for cellular stress caused by sildenafil due to a heterozygous mutation in PDE6. Sildenafil caused a dose-dependent decrease in electroretinogram (ERG) responses of normal mice which mostly recovered two days post administration. In contrast, rd1(+/-) mice exhibited a significantly reduced photoreceptor and a supernormal bipolar cell response to sildenafil within 1 h of treatment. Carrier mice retinae took two weeks to return to baseline levels suggesting sildenafil has direct effects on both the inner and outer retina and these effects differ significantly between normal and carrier mice. Anatomically, an increase in expression of the early apoptotic marker, cytochrome C in rd1(+/-) mice indicated that the effects of sildenafil on visual function may lead to degeneration. The results of this study are significant considering approximately 1 in 50 people are likely to be carriers of recessive traits leading to retinal degeneration. PMID:25239397

  14. A web-based archive for topographic maps of retinal cell distribution in vertebrates.

    PubMed

    Collin, Shaun P

    2008-01-01

    Clinical and Experimental Optometry, in conjunction with Optometrists Association Australia and Professor Shaun P Collin of the University of Queensland, announce the launch of a web-based archive of previously published topographic maps of retinal cell distribution in vertebrates. At present, the archive boasts more than 770 different maps of the distribution of retinal neurons (for example, photoreceptors, bipolar cells, amacrine cells, horizontal cells and ganglion cells) in nearly 200 species within all vertebrate classes (Cephalospidomorpha, Actinopterygii, Sarcopterygii, Amphibia, Reptilia, Aves and Mammalia). The distribution of retinal neurons has been studied for more than 100 years and has become a powerful means of predicting the spatial resolving power of the eye and the retinal regions containing specialisations, such as areae centrales, horizontal streaks and foveae, where increased densities of neurons define the way in which a species visually samples its environment. The location of these retinal specialisations thereby identifies the part(s) of the visual field of critical importance for localising food and mates and for predator surveillance. The distribution of sampling elements even reflects the symmetry of a species' ecological habitat. The archive is a unique collection of most of the currently available retinal maps, which also presents relevant information, where known, about eye size, retinal cell density, retinal orientation, cell number, spatial resolving power and the type of specialisation, in addition to basic physical parameters of each species (body size, weight, sex and developmental stage). The archive is accessible at http://www.optometrists.asn.au/ceo/retinalsearch and will be updated regularly. The powerful database is interactive and freely available, providing the opportunity to upload both published and unpublished topographic maps. Following a review process, previously unpublished maps will be 'published' and available

  15. Primary Reactions in Retinal Proteins

    NASA Astrophysics Data System (ADS)

    Diller, R.

    Conversion of sunlight into energy or information and their storage on a chemical level is essential for life on earth. An important family of chromoproteins performing these tasks is that of retinal binding proteins. Prominent examples are rhodopsin (Rh) [1,2] as the visual pigment in vertebrate and invertebrate animals, the archaeal rhodopsins bacteriorhodopsin (BR) [3] as a light driven proton pump, halorhodopsin (HR) [4,5] as a light driven chloride pump, sensory rhodopsin I and II (SRI, SRII) [6] as photoreceptors, and proteorhodopsin (PR) [7] as another bacterial proton pump.

  16. Chronic ocular hypertension alters local retinal responsiveness.

    PubMed Central

    Ofri, R; Dawson, W W; Foli, K; Gelatt, K N

    1993-01-01

    Electrophysiological responses of the retina and visual cortex to a series of grating stimuli (6-768 minutes of arc) were recorded in seven sessions using normal beagles, 21 sessions using beagles afflicted with inherited ocular hypertension, and 12 sessions using rhesus monkeys. A 15 degrees field centred around the animal's area centralis or fovea was used to stimulate the central retina. A 30 degrees field, centred on the same spot, was then used to stimulate the larger area. Two recording series were completed on each animal, with both field sizes presented in each recording session. The first recording took place 30 minutes after and the second 2 hours after the injection of thiamylal sodium. Only the signals from the toroidal 15 degrees of the retina of the hypertensive dogs were remarkably larger during the second recording (p = 0.001). No significant differences were found between the two recordings from the retinas of normal dogs or monkeys, nor were there any significant differences between the two recordings from above the cortex in any group. Several hypotheses are proposed to explain the basis for the interaction of thiamylal with the more peripheral retinal function in clinically glaucomatous dogs. PMID:8025048

  17. Blood-retinal barrier in hypoxic ischaemic conditions: basic concepts, clinical features and management.

    PubMed

    Kaur, C; Foulds, W S; Ling, E A

    2008-11-01

    The blood-retinal barrier (BRB) plays an important role in the homeostatic regulation of the microenvironment in the retina. It consists of inner and outer components, the inner BRB (iBRB) being formed by the tight junctions between neighbouring retinal capillary endothelial cells and the outer barrier (oBRB) by tight junctions between retinal pigment epithelial cells. Astrocytes, Müller cells and pericytes contribute to the proper functioning of the iBRB. In many clinically important conditions including diabetic retinopathy, ischaemic central retinal vein occlusion, and some respiratory diseases, retinal hypoxia results in a breakdown of the iBRB. Disruption of the iBRB associated with increased vascular permeability, results in vasogenic oedema and tissue damage, with consequent adverse effects upon vision. Factors such as enhanced production of vascular endothelial growth factor (VEGF), NO, oxidative stress and inflammation underlie the increased permeability of the iBRB and inhibition of these factors is beneficial. Experimental studies in our laboratory have shown melatonin to be a protective agent for the iBRB in hypoxic conditions. Although oBRB breakdown can occur in conditions such as accelerated hypertension and the toxaemia of pregnancy, both of which are associated with choroidal ischaemia and in age-related macular degeneration (ARMD), and is a feature of exudative (serous) retinal detachment, our studies have shown that the oBRB remains intact in hypoxic/ischaemic conditions. Clinically, anti-VEGF therapy has been shown to improve vision in diabetic maculopathy and in neovascular ARMD. The visual benefit in both conditions appears to arise from the restoration of BRB integrity with a reduction of retinal oedema. PMID:18940262

  18. Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study.

    PubMed

    Bianchi, Enrica; Ripandelli, Guido; Taurone, Samanta; Feher, Janos; Plateroti, Rocco; Kovacs, Illes; Magliulo, Giuseppe; Orlando, Maria Patrizia; Micera, Alessandra; Battaglione, Ezio; Artico, Marco

    2016-03-01

    Normal human aging and diabetes are associated with a gradual decrease of cerebral flow in the brain with changes in vascular architecture. Thickening of the capillary basement membrane and microvascular fibrosis are evident in the central nervous system of elderly and diabetic patients. Current findings assign a primary role to endothelial dysfunction as a cause of basement membrane (BM) thickening, while retinal alterations are considered to be a secondary cause of either ischemia or exudation. The aim of this study was to reveal any initial retinal alterations and variations in the BM of retinal capillaries during diabetes and aging as compared to healthy controls. Moreover, we investigated the potential role of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines in diabetic retina.Transmission electron microscopy (TEM) was performed on 46 enucleated human eyes with particular attention to alterations of the retinal capillary wall and Müller glial cells. Inflammatory cytokines expression in the retina was investigated by immunohistochemistry.Our electron microscopy findings demonstrated that thickening of the BM begins primarily at the level of the glial side of the retina during aging and diabetes. The Müller cells showed numerous cytoplasmic endosomes and highly electron-dense lysosomes which surrounded the retinal capillaries. Our study is the first to present morphological evidence that Müller cells start to deposit excessive BM material in retinal capillaries during aging and diabetes. Our results confirm the induction of pro-inflammatory cytokines TNF-α and IL-1β within the retina as a result of diabetes.These observations strongly suggest that inflammatory cytokines and changes in the metabolism of Müller glial cells rather than changes in of endothelial cells may play a primary role in the alteration of retinal capillaries BM during aging and diabetes. PMID:26604209

  19. A Novel Form of Progressive Retinal Atrophy in Swedish Vallhund Dogs

    PubMed Central

    Cooper, Ann E.; Ahonen, Saija; Rowlan, Jessica S.; Duncan, Alison; Seppälä, Eija H.; Vanhapelto, Päivi; Lohi, Hannes; Komáromy, András M.

    2014-01-01

    Inherited retinal degenerations, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD), represent leading causes of incurable blindness in humans. This is also true in dogs, where the term progressive retinal atrophy (PRA) is used to describe inherited photoreceptor degeneration resulting in progressive vision loss. Because of the similarities in ocular anatomy, including the presence of a cone photoreceptor-rich central retinal region, and the close genotype-phenotype correlation, canine models contribute significantly to the understanding of retinal disease mechanisms and the development of new therapies. The screening of the pure-bred dog population for new forms of PRA represents an important strategy to establish new large animal models. By examining 324 dogs of the Swedish vallhund breed in seven countries and across three continents, we were able to describe a new and unique form of PRA characterized by the multifocal appearance of red and brown discoloration of the tapetal fundus followed over time by thinning of the retina. We propose three stages of the disease based on the appearance of the ocular fundus and associated visual deficits. Electroretinography revealed a gradual loss of both rod and cone photoreceptor-mediated function in Stages 2 and 3 of the disease. In the few dogs that suffered from pronounced vision loss, night-blindness occurred first in late Stage 2, followed by decreased day-vision in Stage 3. Histologic examinations confirmed the loss of photoreceptor cells at Stage 3, which was associated with the accumulation of autofluorescent material in the adjacent retinal pigment epithelium. Pedigree analysis was suggestive of an autosomal-recessive mode of inheritance. Mutations in six known canine retinal degeneration genes as well as hypovitaminosis E were excluded as causes of the disease. The observed variability in the age of disease onset and rate of progression suggest the presence of genetic and/or environmental

  20. Evaluation of Retinal Vessel Morphology in Patients with Parkinson's Disease Using Optical Coherence Tomography

    PubMed Central

    Hidding, Ute; Keserü, Matthias; Keserü, Diana; Hassenstein, Andrea; Stemplewitz, Birthe

    2016-01-01

    Purpose The retina has been found affected in Parkinson’s disease (PD). It is unclear if this is due to neurodegeneration of local dopamine-dependent retinal cells, a result of central nervous degeneration including the optic nerve or retinal small vessel disease. This study aimed to detect changes of the retinal vasculature in PD patients compared to controls. Methods We examined 49 PD patients and 49 age- and sex-matched healthy controls by spectral domain optical coherence tomography (SD-OCT) with a circular scan centred at the optic disc. Vessels within the retinal nerve fibre layer were identified by an automated algorithm and thereafter manually labelled as artery or vein. Layer segmentation, vessel lumen and direct surrounding tissue were marked automatically with a grey value and the contrast between both values in relation to the surrounding tissue was calculated. The differences in these grey value ratios among subjects were determined and used as an indicator for differences in vessel morphology. Furthermore, the diameters of the veins and arteries were measured and then compared between the groups. Results The contrast of retinal veins was significantly lower in PD patients compared to controls, which indicates changes in vessel morphology in PD. The contrast of arteries was not significantly different. Disease duration, disease stage according to Hoehn and Yahr or age did not influence the grey value ratios in PD patients. Vessel diameter in either veins or arteries did not differ between subject groups. The contrast of retinal veins contralateral to the clinically predominant and first affected side was significantly lower compared to the ipsilateral side. Conclusion Our data show a potential difference of the retinal vasculature in PD patients compared to controls. Vascular changes in the retina of PD patients might contribute to vision-related complaints in PD. PMID:27525728

  1. Honokiol inhibits pathological retinal neovascularization in oxygen-induced retinopathy mouse model

    SciTech Connect

    Vavilala, Divya Teja; O’Bryhim, Bliss E.; Ponnaluri, V.K. Chaithanya; White, R. Sid; Radel, Jeff; Symons, R.C. Andrew; Mukherji, Mridul

    2013-09-06

    Highlights: •Aberrant activation of HIF pathway is the underlying cause of ischemic neovascularization. •Honokiol has better therapeutic index as a HIF inhibitor than digoxin and doxorubicin. •Daily IP injection of honokiol in OIR mouse model reduced retinal neovascularization. •Honokiol also prevents vaso-obliteration, the characteristic feature of the OIR model. •Honokiol enhanced physiological revascularization of the retinal vascular plexuses. -- Abstract: Aberrant activation of the hypoxia inducible factor (HIF) pathway is the underlying cause of retinal neovascularization, one of the most common causes of blindness worldwide. The HIF pathway also plays critical roles during tumor angiogenesis and cancer stem cell transformation. We have recently shown that honokiol is a potent inhibitor of the HIF pathway in a number of cancer and retinal pigment epithelial cell lines. Here we evaluate the safety and efficacy of honokiol, digoxin, and doxorubicin, three recently identified HIF inhibitors from natural sources. Our studies show that honokiol has a better safety to efficacy profile as a HIF inhibitor than digoxin and doxorubicin. Further, we show for the first time that daily intraperitoneal injection of honokiol starting at postnatal day (P) 12 in an oxygen-induced retinopathy (OIR) mouse model significantly reduced retinal neovascularization at P17. Administration of honokiol also prevents the oxygen-induced central retinal vaso-obliteration, characteristic feature of the OIR model. Additionally, honokiol enhanced physiological revascularization of the retinal vascular plexuses. Since honokiol suppresses multiple pathways activated by HIF, in addition to the VEGF signaling, it may provide advantages over current treatments utilizing specific VEGF antagonists for ocular neovascular diseases and cancers.

  2. Advancing Therapeutic Strategies for Inherited Retinal Degeneration: Recommendations From the Monaciano Symposium

    PubMed Central

    Thompson, Debra A.; Ali, Robin R.; Banin, Eyal; Branham, Kari E.; Flannery, John G.; Gamm, David M.; Hauswirth, William W.; Heckenlively, John R.; Iannaccone, Alessandro; Jayasundera, K. Thiran; Khan, Naheed W.; Molday, Robert S.; Pennesi, Mark E.; Reh, Thomas A.; Weleber, Richard G.; Zacks, David N.

    2015-01-01

    Although rare in the general population, retinal dystrophies occupy a central position in current efforts to develop innovative therapies for blinding diseases. This status derives, in part, from the unique biology, accessibility, and function of the retina, as well as from the synergy between molecular discoveries and transformative advances in functional assessment and retinal imaging. The combination of these factors has fueled remarkable progress in the field, while at the same time creating complex challenges for organizing collective efforts aimed at advancing translational research. The present position paper outlines recent progress in gene therapy and cell therapy for this group of disorders, and presents a set of recommendations for addressing the challenges remaining for the coming decade. It is hoped that the formulation of these recommendations will stimulate discussions among researchers, funding agencies, industry, and policy makers that will accelerate the development of safe and effective treatments for retinal dystrophies and related diseases. PMID:25667399

  3. Line-field parallel swept source MHz OCT for structural and functional retinal imaging.

    PubMed

    Fechtig, Daniel J; Grajciar, Branislav; Schmoll, Tilman; Blatter, Cedric; Werkmeister, Rene M; Drexler, Wolfgang; Leitgeb, Rainer A

    2015-03-01

    We demonstrate three-dimensional structural and functional retinal imaging with line-field parallel swept source imaging (LPSI) at acquisition speeds of up to 1 MHz equivalent A-scan rate with sensitivity better than 93.5 dB at a central wavelength of 840 nm. The results demonstrate competitive sensitivity, speed, image contrast and penetration depth when compared to conventional point scanning OCT. LPSI allows high-speed retinal imaging of function and morphology with commercially available components. We further demonstrate a method that mitigates the effect of the lateral Gaussian intensity distribution across the line focus and demonstrate and discuss the feasibility of high-speed optical angiography for visualization of the retinal microcirculation. PMID:25798298

  4. Line-field parallel swept source MHz OCT for structural and functional retinal imaging

    PubMed Central

    Fechtig, Daniel J.; Grajciar, Branislav; Schmoll, Tilman; Blatter, Cedric; Werkmeister, Rene M.; Drexler, Wolfgang; Leitgeb, Rainer A.

    2015-01-01

    We demonstrate three-dimensional structural and functional retinal imaging with line-field parallel swept source imaging (LPSI) at acquisition speeds of up to 1 MHz equivalent A-scan rate with sensitivity better than 93.5 dB at a central wavelength of 840 nm. The results demonstrate competitive sensitivity, speed, image contrast and penetration depth when compared to conventional point scanning OCT. LPSI allows high-speed retinal imaging of function and morphology with commercially available components. We further demonstrate a method that mitigates the effect of the lateral Gaussian intensity distribution across the line focus and demonstrate and discuss the feasibility of high-speed optical angiography for visualization of the retinal microcirculation. PMID:25798298

  5. Demarcation laser photocoagulation induced retinal necrosis and rupture resulting in large retinal tear formation.

    PubMed

    Quezada, Carlos; Pieramici, Dante J; Matsui, Rodrigo; Rabena, Melvin; Graue, Federico

    2015-06-01

    Retinal tears after laser photocoagulation are a rare complication that occurs after intense laser. It is talked about among retina specialist occurring particularly at the end of a surgical case while applying endophotocoagulation; to the best our knowledge, there are no reports in the literature of a large retinal tear induced after attempted in-office demarcation laser photocoagulation (DLP) that simulated a giant retinal tear. DLP has been employed in the management of selected cases of macula sparring rhegmatogenous retinal detachment (RRD). Even though extension of the retinal detachment through the "laser barrier" is considered a failure of treatment, few complications have been described with the use of this less invasive retinal detachment repair technique. We describe a case of a high myopic woman who initially was treated with demarcation laser photocoagulation for an asymptomatic retinal detachment associated with a single horseshoe tear and a full thickness large retinal tear was created where the laser was placed. Intense laser photocoagulation resulted in abrupt laser induced retinal necrosis and rupture creating this large retinal break. Proper laser technique should reduce the risks associated with this procedure. PMID:25770055

  6. The retinal ganglion cell classes of New World primates.

    PubMed

    Yamada, E S; Silveira, L C; Gomes, F L; Lee, B B

    1996-12-01

    In the primate retina there are distinct ganglion cell classes, exhibiting particular morphologies and central projections, each responsible for conveying particular types of visual information to the brain. The chief retinal inputs to the cortex arise from specific ganglion cell classes, M-ganglion cells, responsible for carrying the luminance signal, and P-ganglion cells, that convey the red-green color opponent signal, as well as high contrast luminance signal. There are other ganglion cell classes, such as small-field bistratified cells, exhibiting dendrites that stratify at two different levels in the inner plexiform layer, which convey the blue-yellow color opponent signal. Most published data concerning primate retinal ganglion cell anatomy and physiology have been obtained from Old World species. Studies on New World monkeys have recently become of interest since they differ from the Old World monkeys with respect to the color vision inheritance pattern. On reviewing retinal ganglion cell layer organization in New World monkeys, it seems that there are more similarities than differences in relation to the Old World monkeys. Diurnal genera of New World monkeys exhibit a well-developed fovea centralis and ganglion cell density peak, as well as peripheral density values which are in the range reported for Old World monkeys and human. Moreover, all the major ganglion cell classes identified in Old World monkeys are also present in New World primates. Up to now, no obvious anatomical differences between dichromats and trichromats have been reported. The only genus that is significantly different from the others is the Aotus. It exhibits lower ganglion cell density in the central retina, and apparently lacks the small-field bistratified cells. PMID:9394516

  7. Genetic linkage studies in autosomal recessive retinitis pigmentosa

    SciTech Connect

    Mansfield, D.C.; Teague, P.W.; Barber, A.

    1994-09-01

    Autosomal recessive retinitis pigmentosa (arRP) is a severe retinal dystrophy characterized by night blindness, progressive constriction of the visual fields and loss of central vision in the fourth or fifth decades. The frequency of this form of retinitis pigmentosa (RP) varies in different populations. Mutations within the rhodopsin, cyclic GMP phosphodiesterase-{beta} subunit and cGMP-gated channel genes have been reported in some arRP families. The genetic loci responsible for the majority of cases have yet to be identified. Genetic heterogeneity is likely to be extensive. In order to minimize the amount of genetic heterogenity, a set of arRP families was ascertained within the South-Central Sardinian population, in which 81% of families with a known mode of inheritance show an autosomal recessive form of RP. The Sardinian population is an ethnic {open_quotes}outlier{close_quotes}, having remained relatively isolated from mainland and other cultures. Genetic linkage data has been obtained in a set of 11 Sardinian arRP kindreds containing 26 affected members. Under the assumption of genetic homogeneity, no evidence of linkage was found in the arRP kindreds using 195 markers, which excluded 62% of the genome (Z<-2). Positive lod scores were obtained with D14S80 which showed no recombination in a subset of 5 families. Heterogeneity testing using D14S80 and arRP showed no significant evidence of heterogeneity (p=0.18) but evidence of linkage ({chi}{sup 2}=3.64, p=0.028). We are currently screening the neural retina-specific leucine zipper gene (NRL) in 14q11 for mutations as a candidate locus.

  8. The clinical features of retinal disease due to a dominant mutation in RPE65

    PubMed Central

    Hull, Sarah; Mukherjee, Rajarshi; Holder, Graham E.; Moore, Anthony T.

    2016-01-01

    Purpose To present a detailed phenotypic and molecular study of two families with autosomal dominant RPE65-related retinal dystrophy. Methods Five patients from two families were ascertained from the retinal clinics of a tertiary referral center. Phenotyping included retinal imaging and electrophysiological testing. Bidirectional Sanger sequencing of exon 13 of RPE65 and its intron–exon boundaries was performed on all reported patients and segregation confirmed in available relatives. The main outcome measures were the results of an ophthalmic examination and investigation and molecular genetic analysis. Results Four affected patients from two families presented with nyctalopia and central visual disturbance in adulthood progressing to severe visual loss by the fifth to eighth decades. The patients had extensive chorioretinal atrophy with a relatively preserved anterior retina. In the second family, one patient had bilateral, vitelliform-like foveal lesions consistent with adult onset vitelliform macular dystrophy and no peripheral retinal changes. These unrelated families were both heterozygous for c.1430A>G (p.Asp477Gly). One unaffected family member also tested positive for this mutation but had good vision at age 80 years. Conclusions Autosomal dominant retinal dystrophy resembling choroideremia can arise from a heterozygous mutation in RPE65. It may manifest with mild disease or be non-penetrant. Awareness of these unusual presentations can facilitate targeted molecular investigation. PMID:27307694

  9. Persistent inflammatory state after photoreceptor loss in an animal model of retinal degeneration.

    PubMed

    Noailles, Agustina; Maneu, Victoria; Campello, Laura; Gómez-Vicente, Violeta; Lax, Pedro; Cuenca, Nicolás

    2016-01-01

    Microglia act as the resident immune cells of the central nervous system, including the retina. In response to damaging stimuli microglia adopt an activated state, which can progress into a phagocytic phenotype and play a potentially harmful role by eliciting the expression and release of pro-inflammatory cytokines. The aim of the present study was to assess longitudinal changes in microglia during retinal degeneration in the homozygous P23H rat, a model of dominant retinitis pigmentosa. Microglial phenotypes, morphology and density were analyzed by immunohistochemistry, flow cytometry, and cytokine antibody array. In addition, we performed electroretinograms to evaluate the retinal response. In the P23H retina, sclera, choroid and ciliary body, inflammatory cells increased in number compared with the control at all ages analyzed. As the rats became older, a higher number of amoeboid MHC-II(+) cells were observed in the P23H retina, which correlated with an increase in the expression of pro-inflammatory cytokines. These findings suggest that, in the P23H model, retinal neuroinflammation persists throughout the rat's life span even after photoreceptor depletion. Therefore, the inclusion of anti-inflammatory drugs at advanced stages of the neurodegenerative process may provide better retinal fitness so the remaining cells could still be used as targets of cellular or gene therapies. PMID:27624537

  10. Amyloid β accumulation and inner retinal degenerative changes in Alzheimer's disease transgenic mouse.

    PubMed

    Gupta, Vivek K; Chitranshi, Nitin; Gupta, Veer B; Golzan, Mojtaba; Dheer, Yogita; Wall, Roshana Vander; Georgevsky, Dana; King, Anna E; Vickers, James C; Chung, Roger; Graham, Stuart

    2016-06-01

    The APP-PS1ΔE9 mouse model of Alzheimer's disease (AD) exhibits age dependent amyloid β (Aβ) plaque formation in their central nervous system due to high expression of mutated human APP and PSEN1 transgenes. Here we evaluated Aβ deposition and changes in soluble Aβ accumulation in the retinas of aged APP-PS1 mice using a combination of immunofluorescence, retinal flat mounts and western blotting techniques. Aβ accumulation in the retina has previously been shown to be associated with retinal ganglion cell apoptosis in animal models of glaucoma. This study investigated changes in the inner retinal function and structure in APP-PS1 mice using electrophysiology and histological approaches respectively. We report for the first time a significant decline in scotopic threshold response (STR) amplitudes which represents inner retinal function in transgenic animals compared to the wild type counterparts (p<0.0001). Thinning of the retina particularly involving inner retinal layers and reduction in axonal density in the optic nerve was also observed. TUNEL staining was performed to examine neuronal apoptosis in the inner retina. Intraocular pressure (IOP) measurements showed that APP-PS1ΔE9 mice had a slightly elevated IOP, but the significance of this finding is not yet known. Together, these results substantiate previous observations and highlight that APP-PS1ΔE9 mice show evidence of molecular, functional and morphological degenerative changes in the inner retina. PMID:27133194

  11. Relation of Blood Pressure to Retinal Vessel Diameter in Type 1 Diabetes Mellitus

    PubMed Central

    Klein, Ronald; Myers, Chelsea E.; Klein, Barbara E. K.; Zinman, Bernard; Gardiner, Robert; Suissa, Samy; Sinaiko, Alan R.; Donnelly, Sandra M.; Goodyer, Paul; Strand, Trudy; Mauer, Michael

    2009-01-01

    Objective To examine the relationship of blood pressure (BP) and use of angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEI) to retinal vessel diameter in normotensive, normoalbuminuric persons with type 1 diabetes mellitus (T1DM). Design Randomized controlled clinical trial. Participants Persons with T1DM and gradable fundus photographs both at baseline (n=147) and 5-year follow-up (n=124). Methods Clinic and 24-hour ambulatory BPs (ABP) were measured. Retinal arteriolar and venular diameters were measured using a computer-assisted technique. Individual arteriolar and venular measurements were combined into summary indices that reflect the average retinal arteriolar (central retinal arteriolar equivalent [CRAE]) and venular (central retinal venular equivalent [CRVE]) diameter of an eye, respectively. Main Outcome Measures CRAE and CRVE. Results While controlling for age, study site, glycosylated hemoglobin and ambulatory pulse rate, daytime ambulatory systolic (-0.29 μm effect per 1mmHg, P=.02) and daytime ambulatory diastolic (-0.44 μm effect per 1mmHg, P=.04), nighttime ambulatory systolic (-0.27 μm effect per 1mmHg, P=.03), and 24-hour ambulatory systolic BP (-0.31 μm effect per 1mmHg, P=.03) were cross-sectionally associated with a smaller CRAE. While controlling for age, study site, glycosylated hemoglobin, ambulatory pulse rate and baseline CRAE, no BP measure was associated with a change in CRAE or CRVE over 5 years of follow-up. Treatment with losartan or enalapril was not associated with a statistically significant change in CRAE or CRVE. Conclusions ACEI or ARB therapy does not affect retinal arteriolar or venular diameter in normotensive persons with T1DM. PMID:20142543

  12. Measurement of retinal blood velocity

    NASA Astrophysics Data System (ADS)

    Winchester, Leonard W., Jr.; Chou, Nee-Yin

    2006-02-01

    A fundus camera was modified to illuminate the retina of a rabbit model with low power laser light in order to obtain laser speckle images. A fast-exposure charge-coupled device (CCD) camera was used to capture laser speckle images of the retina. Image acquisition was synchronized with the arterial pulses of the rabbit to ensure that all images are obtained at the same point in the cardiac cycle. The rabbits were sedated and a speculum was inserted to prevent the eyelid from closing. Both albino (New Zealand; pigmented (Dutch belted) rabbits were used in the study. The rabbit retina is almost avascular. The measurements are obtained for choroidal tissue as well as retinal tissue. Because the retina is in a region of high metabolism, blood velocity is strongly affected by blood oxygen saturation. Measurements of blood velocity obtained over a wide range of O II saturations (58%-100%) showed that blood velocity increases with decreasing O II saturation. For most experiments, the left eye of the rabbit was used for laser measurements whereas the right eye served as a control. No observable difference between pre- and post-experimented eye was noted. Histological examinations of retinal tissue subjected to repeated laser measurements showed no indication of tissue damage.

  13. Fixation strategies for retinal immunohistochemistry.

    PubMed

    Stradleigh, Tyler W; Ishida, Andrew T

    2015-09-01

    Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons. PMID:25892361

  14. Fixation Strategies For Retinal Immunohistochemistry

    PubMed Central

    Stradleigh, Tyler W.; Ishida, Andrew T.

    2015-01-01

    Immunohistochemical and ex vivo anatomical studies have provided many glimpses of the variety, distribution, and signaling components of vertebrate retinal neurons. The beauty of numerous images published to date, and the qualitative and quantitative information they provide, indicate that these approaches are fundamentally useful. However, obtaining these images entailed tissue handling and exposure to chemical solutions that differ from normal extracellular fluid in composition, temperature, and osmolarity. Because the differences are large enough to alter intercellular and intracellular signaling in neurons, and because retinae are susceptible to crush, shear, and fray, it is natural to wonder if immunohistochemical and anatomical methods disturb or damage the cells they are designed to examine. Tissue fixation is typically incorporated to guard against this damage and is therefore critically important to the quality and significance of the harvested data. Here, we describe mechanisms of fixation; advantages and disadvantages of using formaldehyde and glutaraldehyde as fixatives during immunohistochemistry; and modifications of widely used protocols that have recently been found to improve cell shape preservation and immunostaining patterns, especially in proximal retinal neurons. PMID:25892361

  15. Suitability of UK Biobank Retinal Images for Automatic Analysis of Morphometric Properties of the Vasculature

    PubMed Central

    MacGillivray, Thomas J; Cameron, James R.; Zhang, Qiuli; El-Medany, Ahmed; Mulholland, Carl; Sheng, Ziyan; Dhillon, Bal; Doubal, Fergus N.; Foster, Paul J.

    2015-01-01

    Purpose To assess the suitability of retinal images held in the UK Biobank - the largest retinal data repository in a prospective population-based cohort - for computer assisted vascular morphometry, generating measures that are commonly investigated as candidate biomarkers of systemic disease. Methods Non-mydriatic fundus images from both eyes of 2,690 participants - people with a self-reported history of myocardial infarction (n=1,345) and a matched control group (n=1,345) - were analysed using VAMPIRE software. These images were drawn from those of 68,554 UK Biobank participants who underwent retinal imaging at recruitment. Four operators were trained in the use of the software to measure retinal vascular tortuosity and bifurcation geometry. Results Total operator time was approximately 360 hours (4 minutes per image). 2,252 (84%) of participants had at least one image of sufficient quality for the software to process, i.e. there was sufficient detection of retinal vessels in the image by the software to attempt the measurement of the target parameters. 1,604 (60%) of participants had an image of at least one eye that was adequately analysed by the software, i.e. the measurement protocol was successfully completed. Increasing age was associated with a reduced proportion of images that could be processed (p=0.0004) and analysed (p<0.0001). Cases exhibited more acute arteriolar branching angles (p=0.02) as well as lower arteriolar and venular tortuosity (p<0.0001). Conclusions A proportion of the retinal images in UK Biobank are of insufficient quality for automated analysis. However, the large size of the UK Biobank means that tens of thousands of images are available and suitable for computational analysis. Parametric information measured from the retinas of participants with suspected cardiovascular disease was significantly different to that measured from a matched control group. PMID:26000792

  16. Expression Profiling after Retinal Detachment and Reattachment: A Possible Role for Aquaporin-0

    PubMed Central

    Farjo, Rafal; Peterson, Ward M.; Naash, Muna I.

    2009-01-01

    Purpose Retinal detachment (RD) is associated with acute visual loss caused by anatomic displacement of the photoreceptors and with chronic visual loss/disturbance caused by retinal remodeling and photoreceptor cell death, which may occur even after successful reattachment. The P2Y2 receptor agonist INS37217 improves the rate of retinal reattachment in animal models of induced RD, and has been shown to also significantly enhance the rate of ERG recovery in a mouse model of RD. The identification of genes modulated by INS37217 may allow further drug discovery for treating RD and edema. Methods To identify genes involved in RD and subsequent reattachment, a retinal microarray screen was performed using a mouse model of RD in the presence or absence of INS37217. Results Ninety-two genes were identified as differentially expressed across three time points, most of which were upregulated in the presence of this agonist. Furthermore, it was shown that RD alters the expression of aquaporin-0 (AQP-0), and this modulation is prevented by treatment with INS37217. The presence of AQP-0 in retinal bipolar cells was also demonstrated, whereas it was previously thought to be specific to the lens. Mice lacking functional alleles of AQP-0 had a photo-transduction deficit as assessed by electroretinography; however, their photoreceptor structure was normal, indicative of a problem with signal transmission between neurons. Conclusions This study establishes the genes involved in RD and reattachment, and also demonstrates for the first time a physiologically significant role for AQP-0 in retinal function. PMID:18234993

  17. A mechanical model of retinal detachment

    NASA Astrophysics Data System (ADS)

    Chou, Tom; Siegel, Michael

    2012-08-01

    We present a model of the mechanical and fluid forces associated with exudative retinal detachments where the retinal photoreceptor cells separate, typically from the underlying retinal pigment epithelium (RPE). By computing the total fluid volume flow arising from transretinal, vascular and RPE pump currents, we determine the conditions under which the subretinal fluid pressure exceeds the maximum yield stress holding the retina and RPE together, giving rise to an irreversible, extended retinal delamination. We also investigate localized, blister-like retinal detachments by balancing mechanical tension in the retina with both the retina-RPE adhesion energy and the hydraulic pressure jump across the retina. For detachments induced by traction forces, we find a critical radius beyond which the blister is unstable to growth. Growth of a detached blister can also be driven by inflamed lesions in which the tissue has a higher choroidal hydraulic conductivity, has insufficient RPE pump activity, or has defective adhesion bonds. We determine the parameter regimes in which the blister either becomes unstable to growth, remains stable and finite-sized, or shrinks, allowing possible healing. The corresponding stable blister radius and shape are calculated. Our analysis provides a quantitative description of the physical mechanisms involved in exudative retinal detachments and can help guide the development of retinal reattachment protocols or preventative procedures.

  18. Retinal microvascular network attenuation in Alzheimer's disease

    PubMed Central

    Williams, Michael A.; McGowan, Amy J.; Cardwell, Chris R.; Cheung, Carol Y.; Craig, David; Passmore, Peter; Silvestri, Giuliana; Maxwell, Alexander P.; McKay, Gareth J.

    2015-01-01

    Introduction Cerebral small-vessel disease has been implicated in the development of Alzheimer's disease (AD). The retinal microvasculature enables the noninvasive visualization and evaluation of the systemic microcirculation. We evaluated retinal microvascular parameters in a case-control study of AD patients and cognitively normal controls. Methods Retinal images were computationally analyzed and quantitative retinal parameters (caliber, fractal dimension, tortuosity, and bifurcation) measured. Regression models were used to compute odds ratios (OR) and confidence intervals (CI) for AD with adjustment for confounders. Results Retinal images were available in 213 AD participants and 294 cognitively normal controls. Persons with lower venular fractal dimension (OR per standard deviation [SD] increase, 0.77 [CI: 0.62–0.97]) and lower arteriolar tortuosity (OR per SD increase, 0.78 [CI: 0.63–0.97]) were more likely to have AD after appropriate adjustment. Discussion Patients with AD have a sparser retinal microvascular network and retinal microvascular variation may represent similar pathophysiological events within the cerebral microvasculature of patients with AD. PMID:26634224

  19. Optical Coherence Tomography Angiography in Retinal Diseases

    PubMed Central

    Chalam, K. V.; Sambhav, Kumar

    2016-01-01

    Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases. PMID:27195091

  20. Optical Coherence Tomography Angiography in Retinal Diseases.

    PubMed

    Chalam, K V; Sambhav, Kumar

    2016-01-01

    Optical coherence tomography angiography (OCTA) is a new, non-invasive imaging system that generates volumetric data of retinal and choroidal layers. It has the ability to show both structural and blood flow information. Split-spectrum amplitude-decorrelation angiography (SSADA) algorithm (a vital component of OCTA software) helps to decrease the signal to noise ratio of flow detection thus enhancing visualization of retinal vasculature using motion contrast. Published studies describe potential efficacy for OCTA in the evaluation of common ophthalmologic diseases such as diabetic retinopathy, age related macular degeneration (AMD), retinal vascular occlusions and sickle cell disease. OCTA provides a detailed view of the retinal vasculature, which allows accurate delineation of microvascular abnormalities in diabetic eyes and vascular occlusions. It helps quantify vascular compromise depending upon the severity of diabetic retinopathy. OCTA can also elucidate the presence of choroidal neovascularization (CNV) in wet AMD. In this paper, we review the knowledge, available in English language publications regarding OCTA, and compare it with the conventional angiographic standard, fluorescein angiography (FA). Finally, we summarize its potential applications to retinal vascular diseases. Its current limitations include a relatively small field of view, inability to show leakage, and tendency for image artifacts. Further larger studies will define OCTA's utility in clinical settings and establish if the technology may offer a non-invasive option of visualizing the retinal vasculature, enabling us to decrease morbidity through early detection and intervention in retinal diseases. PMID:27195091

  1. Infant acute life-threatening event--dysphagic choking versus nonaccidental injury.

    PubMed

    Barnes, Patrick D; Galaznik, John; Gardner, Horace; Shuman, Mark

    2010-03-01

    A 4-month-old male infant presented to the emergency room with a history of choking while bottle feeding at home, and was found by emergency medical services (EMS) to be apneic and pulseless. He subsequently developed disseminated intravascular coagulopathy and died. Com