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Retinopathy
Kinds of Retinopathy Terms modified by Retinopathy Selected AbstractsPOSTPRANDIAL HYPERGLYCEMIA IS AN INDEPENDENT RISK FOR RETINOPATHY IN ELDERLY PATIENTS WITH TYPE 2 DIABETES MELLITUS, ESPECIALLY IN THOSE WITH NEAR-NORMAL GLYCOSYLATED HEMOGLOBINJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2010Toru Aizawa PhD No abstract is available for this article. [source] UPREGULATED ENDOTHELIN SYSTEM IN DIABETIC VASCULAR DYSFUNCTION AND EARLY RETINOPATHY IS REVERSED BY CPU0213 AND TOTAL TRITERPENE ACIDS FROM FRUCTUS CORNICLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 12 2007Wei Su SUMMARY 1The aims of the present study were to examine whether: (i) upregulation of the endothelin (ET) pathway is involved in impairment of vascular relaxation and early retinopathy in diabetic rats; and (ii) vascular and retinal abnormalities respond to the total triterpene acid (TTA) isolated from Fructus Corni compared with responses to the novel endothelin receptor antagonist CPU0213 and aminoguanidine (AMG), a special antagonist for advanced glycation end-products (AGE) and inducible nitric oxide synthase (iNOS). 2Male Sprague-Dawley rats were randomized into five groups, namely a normal control and four diabetic groups, which included an untreated diabetic group and groups treated with AMG (100 mg/kg, i.g.), CPU0213 (30 mg/kg, s.c.) or TTA (50 mg/kg, i.g.). Diabetes was induced by single injection of streptozotocin (60 mg/kg, i.p.) on the 1st day. The mRNA expression of prepro-endothelin-1 (ppET-1), endothelin-converting enzyme (ECE) and iNOS in the thoracic aorta and mRNA for ETA receptors and iNOS in the retina were detected by reverse transcription,polymerase chain reaction. Vasorelaxation to acetylcholine (ACh) and functional assessment of nitric oxide (NO) bioavailability was determined in the thoracic aorta. 3We observed upregulated mRNA expression of iNOS, ppET-1 and ECE in the thoracic aorta and upregulated mRNA for the ETA receptor and iNOS in the retina in the untreated diabetic group. Vasodilatation mediated by ACh and NO bioavailability were markedly reduced in the thoracic aorta compared with the normal control group. These abnormalities were essentially reversed by TTA, CPU0213 or AMG, with the exception with that AMG did not modify vasodilatation to ACh. 4These data suggest that upregulation of gene transcription of the ET system mediates depressed vasorelaxation, NO bioavailability and changes in iNOS and ETA receptors that reflect early retinopathy in diabetic rats. Total triterpene acid, in terms of pharmacological properties resembling the endothelin receptor antagonist CPU0213, is effective in normalizing expression of the ET system and iNOS in early diabetic retinopathy and vasculaopathy. [source] Hereditary Degenerative Retinopathies: Optimism for Somatic Gene TherapyIUBMB LIFE, Issue 6 2000Barkur S. Shastry Abstract Retinitis pigmentosa comprises a large and exceptionally heterogeneous group of hereditary disorders of the retina. As a result of an extensive investigation around the world, primary genetic lesions have been described in many genes. Some of these genes encode enzymes that are involved in the signal transduction pathway. On the basis of in vitro functional assays and standard transgenic and knock-out experiments, it has been proposed that normal cell functions are disrupted because of an abnormal protein-folding and metabolic errors or structural defects in the membrane. This ultimately leads to a gene-mediated cell death known as apoptosis. Various gene transfer approaches using mouse models further suggest that the degeneration can be rescued to some extent. Although many questions remain to be answered, investigations during the last 10 years have enormously increased our understanding of this exceptionally heterogeneous disorder and give hope for an effective gene therapy and a possible cure. [source] Issues regarding quality assurance in the English National Screening Programme for Sight-threatening Diabetic Retinopathy: response to paper by C. Arun et al., ,Establishing ongoing quality assurance in a retinal screening programme'DIABETIC MEDICINE, Issue 6 2007L. Garvican No abstract is available for this article. [source] Practice Characteristics and HMO Enrollee Satisfaction with Specialty Care: An Analysis of Patients with Glaucoma and Diabetic RetinopathyHEALTH SERVICES RESEARCH, Issue 4 2003José J. Escarce Background. The specialist's role in caring for managed care patients is likely to grow. Thus, assessing the correlates of patient satisfaction with specialty care is essential. Objective. To examine the association between characteristics of eye care practices and satisfaction with eye care among working age patients with open-angle glaucoma (OAG) or diabetic retinopathy (DR). Subjects/Study Setting. A total of 913 working age patients with OAG or DR enrolled in six commercial managed care health plans. The patients were treated in 144 different eye care practices. Study Design. We used a patient survey to obtain information on patient characteristics and satisfaction with eye care, measured by scores on satisfaction subscales of the 18-item Patient Satisfaction Questionnaire. We used a survey of eye care practices to obtain information on practice characteristics, including provider specialties, practice organization, financial features, and utilization and quality management systems. We estimated logistic regression models to assess the association of patient and practice characteristics with high levels of patient satisfaction. Principal Findings. Treatment in a practice with a glaucoma specialist (for OAG patients) or a retina specialist (for DR patients) was associated with higher satisfaction, whereas treatment in a practice that obtained a high proportion of its revenues from capitation payments or in a group practice where providers obtained a high proportion of their incomes from bonuses was associated with lower satisfaction. Conclusions. Many eye care patients prefer to be treated by specialists with expertise in their conditions. Financial arrangement features of eye care practices also are associated with patient satisfaction with care. The most likely mechanisms underlying these associations are effects on provider behavior and satisfaction, which in turn influence patient satisfaction. Managed care plans and provider groups should aim to minimize the negative impact of managed care features on patient satisfaction. [source] Arteriolar Involvement in the Microvascular Lesions of Diabetic Retinopathy: Implications for PathogenesisMICROCIRCULATION, Issue 1 2007TOM A. GARDINER ABSTRACT Diabetic retinopathy (DR) is the most widespread complication of diabetes mellitus and a major cause of blindness in the working population of developed countries. The clinicopathology of the diabetic retina has been extensively studied, although the relative contribution of the various biochemical and molecular sequelae of hyperglycemia remains ill defined. Many neural and microvascular abnormalities occur in the retina of short-term diabetic animals but it remains uncertain how closely these acute changes relate to chronic human disease. It is important to determine the relationship between alterations observed within the first weeks or months in short-term animal models, and human disease, where clinically manifest retinopathy occurs only after durations of diabetes measured in years. This review is focused on the retinal microvasculature, although it should be appreciated that pathological changes in this system often occur in parallel with abnormalities in the neural parenchyma that may be derivative or even causal. Nevertheless, it is useful to reevaluate the microvascular lesions that are manifest in the retina during diabetes in humans and long-term animal models, since in addition to providing useful clues to the pathogenic basis of DR as a disease entity, it is in the deterrence of such changes that the efficacy of any novel treatment regimes will be measured. In particular, an emphasis will be placed on the relatively unappreciated role of arteriolar dysfunction in the clinical manifestations and pathology of this disease. [source] Treatment-induced diabetic neuropathy: A reversible painful autonomic neuropathyANNALS OF NEUROLOGY, Issue 4 2010Christopher H. Gibbons MD Objective To describe the natural history, clinical, neurophysiological, and histological features, and outcomes of diabetic patients presenting with acute painful neuropathy associated with glycemic control, also referred to as insulin neuritis. Methods Sixteen subjects presenting with acute painful neuropathy had neurological and retinal examinations, laboratory studies, autonomic testing, and pain assessments over 18 months. Eight subjects had skin biopsies for evaluation of intraepidermal nerve fiber density. Results All subjects developed severe pain within 8 weeks of intensive glucose control. There was a high prevalence of autonomic cardiovascular, gastrointestinal, genitourinary, and sudomotor symptoms in all subjects. Orthostatic hypotension and parasympathetic dysfunction were seen in 69% of subjects. Retinopathy worsened in all subjects. Reduced intraepidermal nerve fiber density (IENFD) was seen in all tested subjects. After 18 months of glycemic control, there were substantial improvements in pain, autonomic symptoms, autonomic test results, and IENFD. Greater improvements were seen after 18 months in type 1 versus type 2 diabetic subjects in autonomic symptoms (cardiovascular p < 0.01; gastrointestinal p < 0.01; genitourinary p < 0.01) and autonomic function tests (p < 0.01, sympathetic and parasympathetic function tests). Interpretation Treatment-induced neuropathy is characterized by acute, severe pain, peripheral nerve degeneration, and autonomic dysfunction after intensive glycemic control. The neuropathy occurred in parallel with worsening diabetic retinopathy, suggesting a common underlying pathophysiological mechanism. Clinical features and objective measures of small myelinated and unmyelinated nerve fibers can improve in these diabetic patients despite a prolonged history of poor glucose control, with greater improvement seen in patients with type 1 diabetes. ANN NEUROL 2010;67:534,541 [source] The prevalence of diabetic retinopathy in patients with screen-detected type 2 diabetes in Denmark: the ADDITION studyACTA OPHTHALMOLOGICA, Issue 3 2009Toke Bek Abstract. Background:, The prevalence of type 2 diabetes is increasing, but the exact prevalence of the disease and its accompanying late complications are unknown. In the Anglo-Danish-Dutch study of Intensive Treatment in People with Screen-detected Diabetes in Primary Care (ADDITION study), patients with hitherto undiagnosed type 2 diabetes are identified using a stepwise screening strategy in selected general practices. This article reports the occurrence of diabetic retinopathy in this population. Methods:, In Ĺrhus and Copenhagen counties, a total of 12 708 of the persons invited by mail were screened for diabetes mellitus. Consequently, 763 persons with type 2 diabetes were identified; 670 of these (335 from each of the two centres) underwent a general physical examination (including measurement of blood pressure and HbA1c) and an ophthalmological examination (including measurement of visual acuity and fundus photography). Retinopathy was graded from the photographs by counting all retinopathy lesions. Results:, Forty-five (6.8%) of the examined patients had any retinopathy, of which the majority was minimal. No patients had severe non-proliferative or proliferative diabetic retinopathy. There was no significant difference between age, sex and visual acuity among patients with and without retinopathy. However, the patients with retinopathy had significantly higher HbA1c and systolic and diastolic blood pressure than the patients without retinopathy. Conclusion:, Patients with screen-detected diabetes have a low prevalence of diabetic retinopathy and no vision-threatening lesions. Screening for diabetic retinopathy should be focused on those patients who have already been diagnosed with type 2 diabetes during routine clinical practice. [source] Metabolic memory puzzle and progression of diabetic retinopathyACTA OPHTHALMOLOGICA, Issue 2008R KOWLURU Purpose Retinopathy is one of the most feared complications of diabetes. Good glycemic control can inhibit its development, but the effects of good glycemic control on the progression of retinopathy are not immediate. Diabetic patients may take years after re-establishment of good glycemic control to show signs of arrest of its progression. Further, good glycemic control after a profound period of poor glycemic control does not immediately benefit the progression of retinopathy, and the imprinted effects of prior glycemic control produce the long lasting benefits of good glycemic control, thus suggesting a ,metabolic memory' phenomenon. Results Animal models of diabetic retinopathy, including dogs and rats, have duplicated this metabolic memory phenomenon. In rats, histopathology associated with diabetic retinopathy does not stop for at least six months when good glycemic control is initiated six months after induction of diabetes. Increase in retinal oxidative stress and peroxynitrite levels and activation of apoptosis execution enzyme-caspase-3 resist reversal after re-institution of good glycemic control. Hyperglycemia-induced inactivation of retinal glyceraldehyde dehydrogenase that is postulated to activate some of the key pathways associated with the development of diabetic complications remains inactive and covalently modified, and pro-inflammatory markers elevated. Conclusion This suggests that the process of metabolic memory is complex, and multiple pathways contribute to this resistance of diabetic retinopathy to arrest. Understanding the mechanism responsible for the tendency of diabetic retinopathy to progress after reestablishment of good glycemic control should help reveal targets for therapies to prevent its progression. [source] New insights into the pathogenic role of advanced glycation in diabetic retinopathyACTA OPHTHALMOLOGICA, Issue 2008AW STITT Purpose Retinopathy is the most common microvascular complication of diabetes. The clinicopathology of microvascular lesions and neuroglial dysfunction in the diabetic retina have been extensively studied, although the relative contribution of various biochemical sequelae of hyperglycaemia remains ill-defined. The formation and accumulation of advanced glycation endproducts (AGEs) is an important pathogenic pathway in the progression of diabetic retinopathy although some of the cellular and molecular pathologies initiated by these adducts in retinal cells remain unknown. Methods This presentation will cover several aspects of AGE-linked retinal pathology and demonstrate opportunities for therapeutic intervention. The studies outlined will cover a wide range of molecular cell biology approaches using appropriate in vitro and in vivo model systems. Results It will be demonstrated that AGEs form in vivo in the diabetic retina through the reaction of alpha-oxaloaldehydes leading to significant modifications of retinal proteins. Evidence will be presented to demonstrate that these AGEs act as significant effectors of retinal vascular and neuroglial cell dysfunction, leading to pro-inflammatory responses, growth factor imbalance and, ultimately, neurovascular lesions such as blood retinal barrier dysfunction and microvascular degeneration. The protective role of novel AGE-inhibitors will also be shown. Conclusion Evidence now points towards a pathogenic role for advanced glycation in the initiation and progression of diabetic retinopathy and this review lecture will outline the current state of knowledge of AGE-related pathology in the retina at a cellular and molecular level. [source] Micro Incisional Vitrectomy (MIVS): a new device for trocar insertionACTA OPHTHALMOLOGICA, Issue 2008S RIZZO Purpose Despite its clinical advantages, MIVS poses significant challenges in performing airtight incisions especially dealing with 23-gauge system. Aim of this paper was to assess the feasibility of performing 23-g MIVS using an injector system for trocar insertion. Methods 60 consecutive eyes of 56 patients underwent 23-g pp vitrectomy and gas endotamponade for the treatment of Regmatogenous Retinal detachment and Diabetic Prolipherative Retinopathy by the same surgeon (SD). 30 eyes were operated on with standard one-step 23-g and 30 using a prototype of injector holding the same 23-g trocar cannula system. The trocar squeezed into the plunger of the injector. The device had a metallic terminal oriented with a fix angle, allowing the insertion in the settled direction, able to fix the globe and displace the conjunctiva at the same time.Main outcome measure were sclerotomies airtightness, surgical time and complications. Results In the 30 eyes operated with the 23-g ones step system 9 sclerotomies were sutured, in 5 refilling was required. Mean surgical time were 54 minutes. In the 30 eyes operated with the new device, the inserter was easy to apply in all cases and was useful especially in the nasal quadrant. Also dealing with sunken eyes the inclination of the system 5-10° tangential to the sclera was easily achieved. No suture was placed, refilling was needed in 3 cases. Mean surgical time was 45 minutes. No complications due to these device were highlighted. Conclusion The new injector was safe and effective. The device facilitates the insertion manoeuvre allowing easier and quicker trocar positioning helping the airtight wound construction. MIVS success lie in the surgeon's skill but also in the development of the technology and instrumentations. [source] Glycodelin: a novel serum anti-inflammatory marker in type 1 diabetic retinopathy during pregnancyACTA OPHTHALMOLOGICA, Issue 1 2007Sirpa Loukovaara Abstract. Purpose:, Inflammation may play a role in the development of diabetic retinopathy during pregnancy. Glycodelin is a glycoprotein whose secretion from the endometrial glands increases during pregnancy. Glycodelin has immunosuppressive properties thought to play a role in the protection of the fetoplacental unit. We studied the role of glycodelin in the development and progression of retinopathy in type 1 diabetes during pregnancy. Methods:, Retinopathy was graded from fundus photographs in 45 diabetes subjects and nine non-diabetes subjects prospectively during pregnancy. Serum glycodelin concentration was measured by an immunofluorometric assay. Results:, In women with diabetes with progression of retinopathy, serum glycodelin concentration was 263 ng/ml (range 116,505 ng/ml) during the first trimester, 61 ng/ml (range 30,106 ng/ml) during the second trimester, and 29 ng/ml (range 13,53 ng/ml) during the third trimester, compared with values of 595 ng/ml (range 376,870 ng/ml), 104 ng/ml (range 75,228 ng/ml) and 45 ng/ml (range 32,74 ng/ml), respectively, in diabetes subjects without progression (p = 0.005 between the groups). Low glycodelin concentration was associated with progression of diabetic retinopathy in multiple regression analysis. Serum glycodelin concentration was similar in women with and without diabetes throughout pregnancy (p = 0.63 by repeated measures anova). Conclusions:, Low glycodelin concentration is associated with progression of retinopathy in pregnant women with diabetes. A possible causal relationship between low glycodelin levels and progression of retinopathy may be mediated by the immunomodulatory properties of glycodelin. [source] Lack of effect of gender on retinopathy in the mouseCLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 5 2001Rosemary D Higgins MD ABSTRACT Background: The reported effect of gender on retinopathy of prematurity has been controversial. The goal of this study was to determine the effect of gender on oxygen-induced retinopathy in a mouse model. Methods: Oxygen-induced retinopathy was produced in C57BL6 mice by exposure to 75% oxygen from postnatal day (P) 7 for 5 days. Animals were returned to room air on P12 and killed on P17,21. Gender was determined by inspection. Retinopathy was evaluated by a retinopathy scoring system and by quantification of extraretinal neovascular nuclei on retinal sections. Results: Both males and females developed similar degrees of retinopathy. Males had a median total retinopathy score of 9 (25th, 75th quartile: 8, 11) and females had score of 9 (25th, 75th quartile: 7,10). Retinal subscores of blood vessel growth, blood vessel tufts, extraretinal neovascularization, haemorrhage and blood vessel tortuosity were similar in both groups. Males and females had a similar number of neovascular nuclei on retinal sections. Conclusions: Gender does not alter the development of oxygen-induced retinopathy in the C57BL6 mouse. [source] Spontaneous Feline Hypertension: Clinical and Echocardiographic Abnormalities, and Survival RateJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 1 2003Valerie Chetboul Systemic hypertension was diagnosed in 58 of 188 untreated cats referred for evaluation of suspected hypertension-associated ocular, neurologic, cardiorespiratory, and urinary disease, or diseases frequently associated with hypertension (hyperthyroidism and chronic renal failure). Hypertensive cats were significantly older than normotensive subjects (13.0 ± 3.5 years versus 9.6 ± 5.0 years; P < .01), and had a greater prevalence of retinal lesions (48 versus 3%; P < .001), gallop rhythm (16 versus 0%; P < .001), and polyuria-polydipsia (53 versus 29%; P < .01). Blood pressure was significantly higher (P < .001) in cats with retinopathies (262 ± 34 mm Hg) than in other hypertensive animals (221 ± 34 mm Hg). Hypertensive cats had a thicker interventricular septum (5.8 ± 1.7 versus 3.7 ± 0.64 mm; P < .001) and left ventricular free wall (6.2 ± 1.6 versus 4.1 ± 0.51 mm; P < .001) and a reduced diastolic left ventricular internal diameter (13.5 ± 3.2 versus 15.8 ± 0.72 mm; P < .001) than control cats. Left ventricular geometry was abnormal in 33 of 39 hypertensive subjects. No significant difference was found in age or blood pressure at the initial visit between cats that died or survived over a 9-month period after initial diagnosis of hypertension. Mean survival times were not significantly different between hypertensive cats with normal and abnormal left ventricular patterns. Further prospective studies are needed to clearly identify the factors involved in survival time in hypertensive cats. [source] 4412: Immunohistochemistry and Western blot methodologies to evaluate neuroprotective agents in models of retinopathiesACTA OPHTHALMOLOGICA, Issue 2010K THERMOS Purpose Many retinopathies that lead to visual loss and blindness are characterized by neovascularization and neural retinal defects, such as a marked loss in retinal neurons and an increase in apoptosis. There are no therapeutic agents for the treatment of the neurodegenerative component of retinal disease. Immunohistochemistry and western blot methodologies were employed to determine retinal viability and to elucidate the putative neuroprotective properties of new therapeutic targets, in animal models of retinopathy (chemical ischemia, excitotoxicity, STZ). Methods To assay retinal viability, the following antibodies for retinal markers were employed in immunohistochemical assays: PKC (rod bipolar cells), ChAT, bNOS, TH (cholinergic-, nitric oxide synthetase-, and dopamine- containing amacrine cells, respectively), calbindin-containing horizontal, amacrine and cone bipolar cells, NFL and MAP1 (ganglion axons and cells, respectively). Antibodies against various pro-survival or pro-death molecules (western blots), as well as the TUNEL-assay, were employed to examine retinal apoptosis and neuroprotection. Results Loss of retinal marker immunoreactivity was differentially observed according to the animal model employed. The neuroprotection of specific retinal neurons by the new therapeutic targets examined (somatostatin and neurosteroids) reflect the existence of protein substrates involved in the mechanism of action of these molecules. Conclusion Immunohistochemical and western blot analysis techniques provide important information on the retinal damage induced by ischemic insults and the neuroprotection afforded by new targets of retinal therapeutics. [source] 3121: Oxygen and treatment of ocular ischemic diseasesACTA OPHTHALMOLOGICA, Issue 2010E STEFANSSON Purpose In ischemia, reduced blood flow results in hypoxia. Hypoxic cells make hypoxia inducible factor (HIF), which controls many of the adaptive responses of tissue to ischemia. This includes vasodilatation, production of vascular endothelial factor (VEGF) with neovascularization and leakage, and finally apoptosis and tissue atrophy. Methods If hypoxia is improved this will reduce the production of VEGF and thereby reduce new vessel formation on one hand and vascular leakage and edeam formation on the other. Several methods are available to improve retinal hypoxia, including laser treatment, vitrectomy, vasodilatory drugs such as carbonic anhydrase inhibitors in addition to breathing oxygen. These treatment methods have been studied by many research groups with invasive polarographic electrodes and optical probes as well as noninvasive oxymetry in human patients and animal subjects. Results We will review experimental and clinical studies, which confirm that oxygen tension of the retina is increased following 1. retinal laser treatment 2. Vitrectomy 3. carbonic anhydrase inhibitors Conclusion Oxygen is the natural control of VEGF. VEGF levels in the retina and other ocular tissues are affected by oxygen levels and ischeimc diseases are currently treated with methods that affect oxygen and consequently VEGF. The addition of anti VEGF drugs to oxygen directed treatment such as laser and vitrectomy further influences the oxygen-HIF-VEGF-neovascularization/edema axis in ischemic retinopathies. [source] 2266: Role of VEGF-isoforms in pathological choroidal angiogenesisACTA OPHTHALMOLOGICA, Issue 2010S VAN DE VEIRE Purpose The aim of this project is to study the specific role of the VEGF-isoforms in pathological angiogenesis, and to investigate the effect of blocking a single isoform on the formation of choroidal neovascularization (CNV). Methods Endothelial and fibroblast cell cultures were made; VEGF 12, 164 or 189 was added to study their effects. VEGF-isoform specific mice (VEGF 120/+, VEGF 164/164 and VEGF188/188 mice) , as well as double transgenic mice (VEGF 120/164, VEGF 164/188 and VEGF120/188 mice) are used to study the role of VEGF-isoforms in pathological angiogenesis. At first, these VEGF-isoform specific mice were backcrossed to a C75Bl/6 background. CNV was induced by placing 3 laser spots at the 9, 12 and 3 o'clock position (100µm spot size, 0.05 s spot duration and 400mW power). Quantification of the area of newly formed blood vessels was determined by retrobulbar dextran linked FITC perfusion. Results Preliminary data in endothelial cell and fibroblast cultures in vitro show that the VEGF121 and VEGF165 isoforms significantly the amount of angiogenesis, whereas the VEGF121 and VEGF189 isoforms play a role in fibrosis. In vivo, the same effects were checked on a fluorescent CD31 and Vimentin immunostaining of the choroids. An inhibition in neovascularization was present in all 3 isoform specific mice, but the effects were comparable. For the moment, mice colonies are being enlarged to repeat experiments and subsequently, these mice are intercrossed to obtain double transgenic mice. Conclusion This study will shed new light on the different role and the inhibition of the VEGF-isoforms in CNV formation during AMD. Thus, our project may open new perspectives for the treatment of various retinopathies that are known to be associated with VEGF upregulation. [source] 4122: Exploring new strategies to record and analyse clinical electroretinogramsACTA OPHTHALMOLOGICA, Issue 2010P LACHAPELLE Purpose Investigate if the combination of time-frequency domain analysis and ERG dipole rotation reveals hidden features of the normal ERG that could be instrumental in the interpretation of nearly extinguished ERG responses. Methods Analyses were conducted on photopic ERGs (Photopic Hills: PH) obtained from normal subjects (n=75) and patients (n=65) affected with various retinopathies. A Discrete Wavelet Transform (DWT) was done on each ERGs and key descriptors (Holder exponent and wavelet coefficient maxima) were calculated. Dipole rotation was obtained by combining 11 gaze positions (0, 8, 16, 24, 32 and 40 degrees nasal or temporal to center) with 4 electrode locations [corneal (CE), lower lid (LL), external (EC) and internal canthi (IC)]. Results The Holder exponent follows a parabola, while some of the local wavelet maxima seem to follow a PH-like like distribution (b-wave and OPs) or a logistic growth function (a-wave). In still recordable pathological ERGs, the wavelet maxima matched that found in normal ERGs evoked at low stimulus intensities while in nearly extinguished ERGs (<10% of normal) the wavelet coefficients were significantly lower. Irrespective of the direction of gaze, there was little variation in DTL ERGs. EC ERGs were the only ones to reverse in polarity (seen 5 degrees nasal to fixation in nasal to temporal shift). Conclusion The parameters obtained with the DWT offers useful and reproducible tools to help identify subtle features of residual ERGs and therefore should allow for a more accurate quantification of low-voltage ERGs responses. Finally, our results suggest that varying the gaze and electrode positions would represent a valuable addition to the recording of clinical ERGs. Funded by NSERC. [source] Mathematical analysis of the cone ERG photopic hill: Clinical applicationsACTA OPHTHALMOLOGICA, Issue 2007P LACHAPELLE Purpose: With brighter stimuli, the photopic ERG b-wave increases to a maximal value and then decreases to a plateau, a feature known as the Photopic Hill (PH). Recently, a mathematical model combining a Gaussian (GF) and a Logistic Growth (LGF) functions was developed to fit the PH (Hamilton et al., Vision Research, in press). We examined if this equation could help us sort out selected retinopathies. Methods: We compared PHs (background: 30 cd.m-2; intensities: -0.8 to 2.84 log cd.sec.m-2) obtained from normals (N=40) and patients (N=20) affected with Congenital Stationary Night Blindness (CSNB), Congenital Postreceptoral Cone Pathway Anomaly (CPCPA) and Retinitis Pigmentosa (RP) with the GL ratio [GL= Gb / (Gb+Vbmax)] were Gb and Vbmax represent the amplitude of the Gaussian and logistic (Vbmax) functions respectively. Results: The normal GL ratio is 0.60 ± 0.08 (mean ± 1SD) compared to ,1.0 in CSNB (almost pure GF) and 0.32±0.08 in CPCP [reduced GF (p<.05) and normal LF (p>.05)] patients. Six of the 8 RP patients had a GL ratio above 0.5 (mean GL= 0.70 ± 0.19) and 2 below (0.28 and 0.41). Of interest, while in some retinopathies, a decline in Gb and Vbmax occurred with disease progression (longitudinal and transversal comparisons), it did not always modify the GL ratio. Conclusions: Human PH can be dissected into two distinct and concomitant phenomena each represented by its own equation. Altghough the retinal origin of the GF and LGF awaits to be confirmed, use of this mathematical approach appears to add valuable information that will further refine the diagnosis of retinal disorders affecting the photopic (cone) pathway. Supported by CIHR and Réseau Vision. [source] Conquering the complex world of human septins: implications for health and diseaseCLINICAL GENETICS, Issue 6 2010EA Peterson Peterson EA and Petty EM. Conquering the complex world of human septins: implications for health and disease. Septins are highly conserved filamentous proteins first characterized in budding yeast and subsequently identified in must eukaryotes. Septins can bind and hydrolyze GTP, which is intrinsically related to their formation of septin hexamers and functional protein interactions. The human septin family is composed of 14 loci, SEPT1-SEPT14, which encode dozens of different septin proteins. Their central GTPase and polybasic domain regions are highly conserved but they diverge in their N-terminus and/or C-terminus. The mechanism by which the different isoforms are generated is not yet well understood, but one can hypothesize that the use of different promoters and/or alternative splicing could give rise to these variants. Septins perform diverse cellular functions according to tissue expression and their interacting partners. Functions identified to date include cell division, chromosome segregation, protein scaffolding, cellular polarity, motility, membrane dynamics, vesicle trafficking, exocytosis, apoptosis, and DNA damage response. Their expression is tightly regulated to maintain proper filament assembly and normal cellular functions. Alterations of these proteins, by mutation or expression changes, have been associated with a variety of cancers and neurological diseases. The association of septins with cancer results from alterations of expression in solid tumors or translocations in leukemias [mixed lineage leukemia (MLL)]. Expression changes in septins have also been associated with neurological conditions such as Alzheimer's and Parkinson's disease, as well as retinopathies, hepatitis C, spermatogenesis and Listeria infection. Pathogenic mutations of SEPT9 were identified in the autosomal dominant neurological disorder hereditary neuralgic amyotrophy (HNA). Human septin research over the past decade has established their importance in cell biology and human disease. Further functional characterization of septins is crucial to our understanding of their possible diagnostic, prognostic, and therapeutic applications. [source] Attenuation of retinal vascular development and neovascularization in transgenic mice over-expressing thrombospondin-1 in the lensDEVELOPMENTAL DYNAMICS, Issue 7 2006Zhifeng Wu Abstract Thrombospondin-1 (TSP1) is an endogenous inhibitor of angiogenesis and induces endothelial cell (EC) apoptosis. To study the role TSP1 plays during vascular development and neovascularization, we assessed the effects of ectopic TSP1 expression in the lens on retinal vascularization in transgenic mice. The TSP1 over-expressing mice showed abnormalities in the development of retinal vasculature. There was a dramatic decrease in the density of superficial and deep vascular plexuses of the retina in transgenic mice. The retinal vessels in TSP1 transgenic mice also appeared nonuniform and abnormal in maturation. We detected an increase in the number of EC undergoing apoptosis, which was compensated, in part, by an increase in cell proliferation in retinal vasculature of TSP1 transgenic mice. The TSP1 transgenic mice also exhibited increased levels of vessel obliteration and a limited preretinal neovascularization during oxygen-induced ischemic retinopathy (OIR). Our results indicate increased expression of TSP1 attenuates normal retinal vascularization and preretinal neovascularization during OIR. Therefore, modulation of TSP1 expression may provide an effective mechanism for regulation of ocular angiogenesis. Developmental Dynamics 235:1908,1920, 2006. © 2006 Wiley-Liss, Inc. [source] Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literatureDIABETES OBESITY & METABOLISM, Issue 4 2010L. Nalysnyk Aim: The objective of this review was to assess the published evidence for an association between glycaemic variability and the development of chronic micro- and macrovascular complications in patients with diabetes mellitus (DM). Methods: A systematic review of English-language literature published from January 1990 through November 2008 was performed. Interventional and observational studies in patients with type 1 or type 2 DM reporting a measure of glycaemic variability and its impact on the development or progression of micro- and macrovascular diabetic complications were assessed. Results: A total of 18 studies ,8 on type 1 DM and 10 on type 2 DM patients,meeting the inclusion criteria were identified. Studies in patients with type 1 DM revealed that glucose variability has little impact on the development of diabetic complications. Only in two of the eight type 1 DM studies did glucose variability have a significant association with microvascular complications, but not with macrovascular complications. Among type 2 DM studies, a significant positive association between glucose variability and the development or progression of diabetic retinopathy, cardiovascular events and mortality was reported in 9 of 10 studies. Only one type 2 DM study reported no association between glucose variability and progression of retinopathy. Conclusions: Based on this overview of the available evidence, there appears to be a signal suggesting that glucose variability, characterized by extreme glucose excursions, could be a predictor of diabetic complications, independent of HbA1c levels, in patients with type 2 DM. Better daily control of blood glucose excursions, especially in the postprandial period, may reduce the risk of these complications. Future prospective trials evaluating and comparing the effect of the control of glycaemic variability on the development of diabetic micro- and macrovascular complications are needed to further strengthen the evidence base. [source] Interactions between microvascular and macrovascular disease in diabetes: pathophysiology and therapeutic implicationsDIABETES OBESITY & METABOLISM, Issue 6 2007Andrew J. Krentz Convention partitions the complications of diabetes into two main subtypes. First are the diabetes-specific microvascular complications of retinopathy, nephropathy and neuropathy; second are the atherothrombotic macrovascular complications that account for the majority of premature deaths. Pathological interactions between microvascular and macrovascular complications, for example, nephropathy and macrovascular disease, are common. Similar mechanisms and shared risk factors drive the development and progression of both small and large vessel disease. This concept has therapeutic implications. Mounting evidence points to the need for multifactorial strategies to prevent vascular complications in subjects with diabetes and/or the metabolic syndrome. We advocate a combined therapeutic approach that addresses small and large vessel disease. Preferential use should be made of drug regimens that (i) maximize vascular protection, (ii) reduce the risk of iatrogenic vascular damage and (iii) minimize the increasing problem of polypharmacy. [source] Novel insulin analogues and its mitogenic potentialDIABETES OBESITY & METABOLISM, Issue 6 2006Ivana Zib Abstract:, Insulin analogues were developed to modify the structure of the human insulin molecule in order to more accurately approximate the endogenous secretion of insulin. With the help of recombinant technology and site-directed mutagenesis, the insulin molecule can be modified to either delay or shorten absorption time, providing better insulin treatment options and facilitating the achievement of glycaemic goals. Changing the structure of the insulin molecule, however, may significantly alter both its metabolic and mitogenic activity. Multiple factors such as residence time on the receptor, dissociation rate, rate of receptor internalization and the degree of phosphorylation of signalling proteins can affect the mitogenic potencies of insulin analogues. Changes in the structure of the insulin have raised concern about the safety of the insulin analogues. For example, questions have emerged about the relationship between the use of insulin lispro and insulin glargine and the progression of diabetic retinopathy. Two studies have shown progression of retinopathy with the use of insulin lispro. However, others have not confirmed these results, and causality could not be proven as progression of retinopathy can occur with rapid improvement in glycaemic control, and methods of assessments among studies were not consistent. Therefore, we examine the metabolic and mitogenic characteristics of the three insulin analogues, insulin lispro, insulin aspart and insulin glargine, that are currently on the market, as well as the two insulin analogues, insulin glulisine and insulin detemir, that are soon going to be available for clinical use. [source] Effects of aminoguanidine and tolrestat on the development of ocular and renal structural changes in experimental diabetic ratsDIABETES OBESITY & METABOLISM, Issue 1 2002Ö. Azal Studies that researched the role of aminoguanidine and tolestat in the prevention of diabetic retinopathy and nephropathy resulted in conflicting data. We investigated the effects of these agents in the prevention of ocular and renal changes in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intravenous injection of STZ in 30 rats. Ten rats that were not given STZ served as non-diabetic control (Group 1). Ten STZ-diabetic rats that were not given any treatment served as diabetic control (Group 2). Groups 3 and 4 were composed of STZ-induced diabetic rats (10 each) that were given tolrestat and aminoguanidine respectively. Eyes and kidneys were examined at the 24th week under electronmicroscopy. Cataract was observed in all six of the surviving rats in Groups 2 and 4, and in one of 6 surviving rats in group 3. Cataract development was lower in Group 3 than Groups 2 and 4. All retinal samples obtained from group 2 demonstrated a number of structural abnormalities, whereas there were no significant ultrastructural changes in groups 3 and 4. Groups 2 and 3 demonstrated mesangial proliferation and expansion, diffuse glomerular basement membrane (GBM) thickening, and focal GBM thickening in the bulb form. Group 4 demonstrated a normally appearing mesangial space, minimal diffuse but no focal GBM thickening. The urinary albumin excretion (UAE) was lower in Group 4 than the other groups. In conclusion, our results suggest that aminoguanidine may be an important agent for the prevention of renal changes, whereas tolrestat may be effective for the prevention of ocular changes in diabetes mellitus. [source] Protective role of pigment epithelium-derived factor (PEDF) in early phase of experimental diabetic retinopathyDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2009Yumiko Yoshida Abstract Background Pigment epithelium-derived factor (PEDF) is the most potent inhibitor of angiogenesis in the mammalian eye, thus suggesting that PEDF may protect against proliferative diabetic retinopathy. However, a role for PEDF in early diabetic retinopathy remains to be elucidated. We investigated here whether and how PEDF could prevent the development of diabetic retinopathy. Methods Streptozotocin-induced diabetic rats were treated with or without intravenous injection of PEDF for 4 weeks. Early neuronal derangements were evaluated by electroretinogram (ERG) and immunofluorescent staining of glial fibrillary acidic protein (GFAP). Expression of PEDF and 8-hydroxydeoxyguanosine (8-OHdG), a marker of oxidative stress, was localized by immunofluorescence. Vascular endothelial growth factor (VEGF) and p22phox expression were evaluated with western blots. Breakdown of blood retinal barrier (BRB) was quantified with fluorescein isothiocynate (FITC)-conjugated dextran. NADPH oxidase activity was measured with lucigenin luminescence. Results Retinal PEDF levels were reduced, and amplitudes of a- and b-wave in the ERG were decreased in diabetic rats, which were in parallel with GFAP overexpression in the Müller cells. Further, retinal 8-OHdG, p22phox and VEGF levels and NADPH oxidase activity were increased, and BRB was broken in diabetic rats. Administration of PEDF ameliorated all of the characteristic changes in early diabetic retinopathy. Conclusions Results suggest that PEDF could prevent neuronal derangements and vascular hyperpermeability in early diabetic retinopathy via inhibition of NADPH oxidase-driven oxidative stress generation. Substitution of PEDF may offer a promising strategy for halting the development of diabetic retinopathy. Copyright © 2009 John Wiley & Sons, Ltd. [source] Different apoptotic responses of human and bovine pericytes to fluctuating glucose levels and protective role of thiamineDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 6 2009Elena Beltramo Abstract Background Vascular cells in diabetes are subjected to daily fluctuations from high to low glucose. We aimed at investigating whether pulsed exposure to different glucose concentrations influences apoptosis in human retinal pericytes (HRP) versus bovine retinal pericytes (BRP), with consequences on the onset of diabetic retinopathy, and the possible protective role of thiamine. Methods BRP and HRP (wild-type and immortalized) were grown in physiological/high glucose for 7 days, and then returned to physiological glucose for another 24, 48 or 72 h. Cells were also kept intermittently at 48-h intervals in high/normal glucose for 8 days, with/without thiamine/benfotiamine. Apoptosis was determined through ELISA, TUNEL, Bcl-2, Bax and p53 expression/concentration. Results Continuous exposure to high glucose increased apoptosis in BRP, but not HRP. BRP apoptosis normalized within 24 h of physiological glucose re-entry, while HRP apoptosis increased within 24,48 h of re-entry. Intermittent exposure to high glucose increased apoptosis in HRP and BRP. Bcl-2/Bax results were consistent with DNA fragmentation, while p53 was unchanged. Thiamine and benfotiamine countered intermittent high glucose-induced apoptosis. Conclusions Human pericytes are less prone to apoptosis induced by persistently high glucose than bovine cells. However, while BRP recover after returning to physiological levels, HRP are more vulnerable to both downwardly fluctuating glucose levels and intermittent exposure. These findings reinforce the hypotheses that (1) glycaemic fluctuations play a role in the development of diabetic retinopathy and (2) species-specific models are needed. Thiamine and benfotiamine prevent human pericyte apoptosis, indicating this vitamin as an inexpensive approach to the prevention and/or treatment of diabetic complications. Copyright © 2009 John Wiley & Sons, Ltd. [source] Insulin glargine and receptor-mediated signalling: clinical implications in treating type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 8 2007Derek Le Roith Abstract Most patients with type 2 diabetes mellitus will eventually require insulin therapy to achieve or maintain adequate glycaemic control. The introduction of insulin analogues, with pharmacokinetics that more closely mimic endogenous insulin secretion, has made physiologic insulin replacement easier to achieve for many patients. However, there are also concerns regarding alteration of binding affinities for the insulin receptor (IR) or insulin-like growth factor-1 receptor (IGF-1R) may increase the mitogenic potential of some analogues. Therefore, this article will review the relevant preclinical and clinical data to assess the mitogenic potential of insulin glargine, a basal insulin analogue, compared with regular human insulin (RHI). Searches of the PubMed database were performed using terms that included ,IR,' ,insulin-like growth factor-1,' ,IGF-1R,' ,type 2 diabetes mellitus,' and ,insulin glargine.' Original articles and reviews of published literature were retrieved and reviewed. Although one study reported increased binding affinity of insulin glargine for the IGF-1R and increased mitogenic potential in cells with excess IGF-1Rs (Saos/B10 osteosarcoma cells), most in vitro binding-affinity and cell-culture studies have demonstrated behaviour of insulin glargine comparable to that of RHI for both IR and IGF-1R binding, insulin signalling, and metabolic and mitogenic potential. Currently published in vivo carcinogenic studies and human clinical trial data have shown that insulin glargine is not associated with increased risk for either cancer or the development or progression of diabetic retinopathy. Copyright © 2007 John Wiley & Sons, Ltd. [source] Retinal capillary basement membrane thickness in diabetic mice genetically modified at the haptoglobin locusDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2007Rachel Miller-Lotan Technion Faculty of Medicine Abstract Background Individuals with diabetes mellitus (DM) homozygous for the haptoglobin (Hp) 1 allele are at decreased risk of retinopathy as compared to DM individuals with the Hp 2 allele. We sought to recapitulate these findings in DM mice genetically modified at the Hp locus. Methods An early morphological characteristic of the microangiopathy seen in diabetic retinal disease is retinal capillary basement membrane (RCBM) thickening. RCBM thickness as assessed by electron microscopy was performed on a total of 12 eyes taken from three mice in each of the four study groups (three eyes from C57Bl/6 Hp 1 and C57Bl/6 Hp 2 mice with and without streptozotocin-induced diabetes). Results The non-parametric Kruskal,Wallis ANOVA test demonstrated that there was a highly significant difference between the four groups of mice (P < 0.0001). Mann,Whitney tests for specific pair-wise comparisons demonstrated that there was no significant difference in the RCBM thickness between Hp 1 and Hp 2 mice (p = 0.70) or between DM Hp 1 and non-DM Hp 1 mice (p = 0.42). However, induction of diabetes resulted in a marked increase in RCBM thickness in Hp 2 mice compared to non-DM Hp 2 mice (p = 0.0004) and compared to DM Hp 1 mice (p = 0.0005). Conclusions A highly significant increase in RCBM thickness was observed in DM mice with the Hp 2 genotype. These data provide important support for association studies done in humans showing an increased prevalence of diabetic retinopathy in individuals with the Hp 2 genotype. Copyright © 2006 John Wiley & Sons, Ltd. [source] ,Lipoproteins, glycoxidation and diabetic angiopathy'DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 5 2004Alicia J. Jenkins Abstract The chronic vascular complications of diabetes (nephropathy, retinopathy and accelerated atherosclerosis) are a major cause of morbidity and premature mortality. In spite of the more widespread availability of intensive diabetes management, approximately one in three people with diabetes develop aggressive complications and over 70% die of atherosclerosis-related diseases. Genetic and acquired factors are likely to be contributory. Potential mediators of vascular damage may include the interrelated processes of lipoprotein abnormalities, glycation, oxidation and endothelial dysfunction. Lipoprotein abnormalities encompass alterations in lipid concentrations, lipoprotein composition and subclass distribution and lipoprotein-related enzymes. Nonenzymatic glycation and oxidative damage to lipoproteins, other proteins and to vascular structures may also be deleterious. As atherosclerosis is a chronic condition commencing in youth, and because clinical events may be silent in diabetes, surrogate measures of vascular disease are important for early identification of diabetic patients with or at high risk of vascular damage, and for monitoring efficacy of interventions. The increasing array of biochemical assays for markers and mediators of vascular damage, noninvasive measures of vascular health, and therapeutic options should enable a reduction in the excessive personal and economic burden of vascular disease in type 1 and type 2 diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||