The Experts below are selected from a list of 20967 Experts worldwide ranked by ideXlab platform
Laura J Balcer - One of the best experts on this subject based on the ideXlab platform.
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evaluating loss of Visual function in multiple sclerosis as measured by low contrast letter acuity
Neurology, 2010Co-Authors: Laura J Balcer, Elliot M FrohmanAbstract:Background: Disturbances in Visual function are common in patients with multiple sclerosis (MS) and are often accompanied by substantial impairments in daily functioning and quality of life. Lesions associated with these impairments frequently involve the afferent Visual pathway. Expert Clinical Opinion: Because these impairments are often not readily apparent on commonly used high-contrast acuity tests, low-contrast charts (e.g., low-contrast Sloan letter charts) have gained validity in the assessment of Visual Dysfunction in patients with MS. Decrements in low-contrast letter acuity are associated with MS and correlate with increasing disability, MRI abnormalities, and reduced retinal nerve fiber layer (RNFL) thickness as measured by optical coherence tomography (OCT). These findings suggest that low-contrast letter acuity testing is a potentially useful addition to disability scales such as the Multiple Sclerosis Functional Composite, serving as another surrogate marker for MS disability. Assessment of RNFL thickness by OCT, which is also associated with Visual impairment, also may be considered for inclusion in clinical trials evaluating treatments for MS. Future Directions: The effects of disease-modifying therapies on Visual Dysfunction in patients with MS have been evaluated only recently. Two phase 3 studies of natalizumab showed that low-contrast letter acuity testing, included as an exploratory outcome, demonstrated treatment effects. Other ongoing studies have incorporated low-contrast acuity and OCT measures of RNFL thickness. The availability and wider use of low-contrast letter acuity tests, in combination with ocular imaging techniques, may improve assessment of treatment efficacy in patients with MS.
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low contrast letter acuity testing captures Visual Dysfunction in patients with multiple sclerosis
Neurology, 2005Co-Authors: Monika Baier, Richard A Rudick, Bianca Weinstockguttman, Gary Cutter, D M Miller, J A Cohen, Michele Mass, Laura J BalcerAbstract:Objective: To evaluate concurrent and predictive validity for low-contrast letter acuity (L-CLA) testing as a candidate Visual component for the Multiple Sclerosis Functional Composite (MSFC). Methods: L-CLA testing was conducted in two MS patient cohorts. In the MSFC Validation Study, 137 participants from a Phase III trial of inteferon beta-1a (Avonex) for relapsing–remitting MS were followed. A second cohort included 65 patients with secondary progressive MS who participated in a substudy of the International MS Secondary Progressive Avonex Controlled Trial (IMPACT). The total number of letters read correctly at four contrast levels (100, 5, 1.25, and 0.6%) was correlated with Expanded Disability Status Scale (EDSS), MSFC, Sickness Impact Profile, Multiple Sclerosis Quality of Life Inventory, and brain parenchymal fraction (BPF), as determined by MRI. Results: Low- and high-contrast letter acuity scores correlated with BPF at follow-up in the MSFC Validation Study (5%: r = 0.40, p r = 0.31, p = 0.0002). L-CLA also correlated with EDSS (5%: r = −0.35, p r = −0.26, p = 0.0003) and MSFC (5%: r = 0.47, p r = 0.45, p p = 0.0142) and the 1.25% ( p = 0.0038) contrast levels, after adjusting for change in MSFC scores from baseline to year 1. Conclusions: Low-contrast letter acuity (L-CLA) scores demonstrate concurrent and predictive validity in patients with relapsing–remitting and secondary progressive multiple sclerosis (MS). L-CLA testing provides additional information relevant to the MS disease process that is not entirely captured by the Multiple Sclerosis Functional Composite.
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contrast letter acuity as a measure of Visual Dysfunction in patients with friedreich ataxia
Journal of Neuro-ophthalmology, 2002Co-Authors: David A Lynch, Jennifer M Farmer, Dustin Rochestie, Laura J BalcerAbstract:BackgroundFriedreich ataxia is a progressive neurodegenerative disorder affecting afferent cerebellar pathways and other neuronal systems, including afferent Visual pathways. A systematic clinical outcome measure for examination of Visual Dysfunction in Friedreich ataxia has not been identified. We
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self reported Visual Dysfunction in multiple sclerosis new data from the vfq 25 and development of an ms specific vision questionnaire
American Journal of Ophthalmology, 2002Co-Authors: Judy A Shea, Steven Galetta, Maureen G Maguire, Dina A Jacobs, Clyde E Markowitz, Laura J BalcerAbstract:Abstract PURPOSE: To examine vision-specific health-related quality of life in a cohort of patients with multiple sclerosis (MS) using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25), and to identify content areas for a brief MS-specific vision questionnaire. DESIGN: Cross-sectional survey. METHODS: The VFQ-25 and a modified version of the Optic Neuritis Treatment Trial (ONTT) Patient Questionnaire were administered by in-person interview to 80 patients at the University of Pennsylvania MS Center. Binocular Visual acuities were obtained following a standard protocol using retroilluminated Early Treatment Diabetic Retinopathy Study charts. RESULTS: Despite a median binocular Visual acuity of 20/16 (20/12.5–20/250), VFQ-25 subscale scores in the MS cohort were significantly lower (worse) compared with those of a published reference group of eye disease-free patients ( P = .0001–0.009, two-tailed t tests). Rank-correlations of VFQ-25 composite (overall) scores with Visual acuity were modest, but significant ( r s = 0.33, P = .003), supporting construct validity for VFQ-25 scores in MS populations. Seven additional aspects of self-reported Visual Dysfunction in MS were also identified. CONCLUSIONS: Patients with MS have a high degree of self-reported Visual Dysfunction that is not entirely captured by Visual acuity. The VFQ-25 is an effective measure of self-reported Visual loss in MS. A brief MS-specific vision questionnaire may provide additional useful information when administered concurrently with the VFQ-25 in future investigations of MS and other neuroophthalmologic disorders.
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self reported Visual Dysfunction in multiple sclerosis results from the 25 item national eye institute Visual function questionnaire vfq 25
Multiple Sclerosis Journal, 2000Co-Authors: Laura J Balcer, Monika Baier, Amy M Kunkle, Richard A Rudick, Bianca Weinstockguttman, N A Simonian, Steven Galetta, Gary Cutter, Maureen G MaguireAbstract:Visual impairment is one of the most common clinical manifestations of Multiple Sclerosis (MS), and is strongly related to overall health-related quality of life (HRQOL) in MS and other disorders. However, the assessment of vision-specific HRQOL in patients with MS has been limited. The purpose of this study was to examine self-reported Visual Dysfunction in a clinically heterogeneous MS cohort using the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25). The VFQ-25 was administered by telephone interview to a subset of participants in a follow-up study to a phase III trial of interferon beta-1a for relapsing-remitting MS. Mean VFQ-25 composite scores and selected sub-scale scores were significantly lower (worse) among patients in our MS cohort (n=35) compared with a published reference group of patients with no history of chronic eye disease (n= 118). These differences were observed despite a relatively younger age and tighter distribution of binocular Visual acuities in the MS cohort Patients with MS in this study thus demonstrated a greater degree of self-reported Visual Dysfunction, as measured by the VFQ-25, compared with an eye disease-free reference group. The VFQ-25 is a potentially useful measure of vision-specific HRQOL in patients with MS.
Richard Bowman - One of the best experts on this subject based on the ideXlab platform.
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the effect of Visual support strategies on the quality of life of children with cerebral palsy and cerebral Visual impairment perceptual Visual Dysfunction in nigeria study protocol for a randomized controlled trial
Trials, 2019Co-Authors: Clare Gilbert, Gordon N Dutton, Roseline Duke, K I Eyong, Kathryn Burton, David Macleod, Richard BowmanAbstract:Background Cerebral Visual impairment (CVI), including perceptual Visual Dysfunction (PVD), is common in children with cerebral palsy (CP). Inventories of questions relating to practical aspects of Visual perception in everyday life, in particular the closed-ended Insight Questions Inventory (IQI), can be used to assess CVI/PVD. Studies linking responses to the inventory with specific Visual support strategies, aimed at modifying the child’s environment and/or behaviour to minimize the impact of the CVI/PVD, have been piloted. The IQI and tailored strategies have not been used in an African population, nor have they been tested in a controlled trial. This trial will compare the effectiveness of the IQI and linked Visual support strategies versus general supportive treatments on the quality of life of children with CVI/PVD and CP through a randomized controlled trial.
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the effect of Visual support strategies on the quality of life of children with cerebral palsy and cerebral Visual impairment perceptual Visual Dysfunction in nigeria study protocol for a randomized controlled trial
Trials, 2019Co-Authors: Clare Gilbert, Gordon N Dutton, Roseline Duke, K I Eyong, Kathryn Burton, David Macleod, Richard BowmanAbstract:Cerebral Visual impairment (CVI), including perceptual Visual Dysfunction (PVD), is common in children with cerebral palsy (CP). Inventories of questions relating to practical aspects of Visual perception in everyday life, in particular the closed-ended Insight Questions Inventory (IQI), can be used to assess CVI/PVD. Studies linking responses to the inventory with specific Visual support strategies, aimed at modifying the child’s environment and/or behaviour to minimize the impact of the CVI/PVD, have been piloted. The IQI and tailored strategies have not been used in an African population, nor have they been tested in a controlled trial. This trial will compare the effectiveness of the IQI and linked Visual support strategies versus general supportive treatments on the quality of life of children with CVI/PVD and CP through a randomized controlled trial. This is a prospective, double-blind, parallel-arm, randomized controlled trial. The primary outcome is change in quality of life scores between the two arms of the trial at 6 weeks, assessed using the Paediatric Quality of Life Inventory (PedsQL) generic 4.0 and CP 3.0 module. All children will undergo baseline assessment including the Open Questions Inventory, IQI, PedsQL 3.0, PedsQL 4.0 generic, and the Strengths and Difficulties Questionnaire (SDQ). Eligible children with CP aged 4 years to < 16 years will be stratified and blocked by the age groups 4–9 and 10 to < 16 years and by Gross Motor Function Classification System (GMFCS) levels 1–3 and 4–5. Families in the intervention arm will receive tailored insight Visual support strategies and telephone calls during the 6-week trial period. The control arm will receive standard treatment and the intervention after the 6-week trial period. Follow-up interviews will be performed in both arms at 6 weeks with a repeat administration of the PedsQL CP 4.0 and 3.0, the IQI and the SDQ. Secondary outcomes include a change in functional vision. This randomized controlled trial will provide evidence of the effectiveness of this intervention for children with CP in a resource-poor setting. Pan African Clinical Trials Registration, PACTR201612001886396 . Registered on 3 December 2016.
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perceptual Visual Dysfunction physical impairment and quality of life in bangladeshi children with cerebral palsy
British Journal of Ophthalmology, 2016Co-Authors: Danny Mitry, Kate Northstone, A Akter, J Jewel, N Khan, Mohammad Muhit, Clare Gilbert, Cathy Williams, Richard BowmanAbstract:Background Cerebral palsy (CP) is the most common cause of motor disability in children and is often accompanied by sensory and/or cognitive impairment. The aim of this study was to characterise Visual acuity impairment, perceptual Visual Dysfunction (PVD) and physical disability in a community-based sample of Bangladeshi children with CP and to assess the impact of these factors on the quality of life of the children. Methods A key informant study was used to recruit children with CP from Sirajganj district. Gross Motor Function Classification System (GMFCS) levels and Visual impairment were assessed by a physiotherapist and an optometrist, respectively. Assessments of Visual perception were performed and standardised questionnaires were administered to each child9s main carer to elicit indicators of PVD and parent-reported health-related quality of life. A generalised linear regression analysis was conducted to assess the determinants of the quality of life scores. Results 180 children were recruited. The median age was 8 years (IQR: 6–11 years); 112 (62%) were male; 57 (32%) had Visual acuity impairment and 95 (53%) had some parent-reported PVD. In analyses adjusted for age, sex, GMFCS and acuity impairment, Visual attention (p Conclusions PVD is an important contributor in reducing quality of life in children with CP, independent of motor disability and acuity impairment. Better characterisation of PVD is important to help design interventions for affected children, which may improve their quality of life.
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perceptual Visual Dysfunction physical impairment and quality of life in bangladeshi children with cerebral palsy supporting information
2016Co-Authors: Danny Mitry, Carlo Kosik Williams, Kate Northstone, A Akter, J Jewel, N Khan, Mohammad Muhit, Clare Gilbert, Richard BowmanAbstract:Questionnaire and practical exercise used in study of perceptual Visual Dysfunction, physical impairment and quality of life.
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cerebral Visual Dysfunction in prematurely born children attending mainstream school
Documenta Ophthalmologica, 2013Co-Authors: Catriona Macintyrebeon, Richard Bowman, David Young, Gordon N Dutton, Kate Mitchell, Judith Simpson, Gunter Loffler, Ruth HamiltonAbstract:Although premature birth is recognised as a cause of cerebral Visual impairment (CVI), which can include cerebral Visual Dysfunction (CVD), the incidence and nature of CVD in prematurely born children is not known. A prospective, controlled investigation was undertaken of forty-six, mainstream primary school children, prematurely born with gestations of 24.0–34.6 weeks, and of 130 control (term-born) children. Assessments were made of IQ, ophthalmic functions, Visual perception and Visual attention. Structured history-taking seeking evidence of behavioural features of CVI used a question inventory. Obstetric, neonatal and paediatric medical histories were documented from case records. Fifteen out of forty-six (33 %) of the prematurely born children—“cluster A”—revealed behaviours corresponding with CVD on cluster analysis of the CVI inventory. The whole prematurely born group performed worse than controls on all Visual perception tests and all four Visual attention tests. Children in cluster A were responsible for this effect, performing worse than controls on all Visual perception and Visual attention tests except Visual closure, while cluster B prematurely born children performed no differently to controls. The prevalence of CVD in these prematurely born children is between 21–47 % (95 % CI), with a pattern similar to “dorsal stream Dysfunction”. Currently available perceptual tests appear to be unable to identify the specific pattern of problems noted in this group. Many studies have provided evidence of cognitive and intellectual Dysfunction in prematurely born children, and it is possible that CVD is a contributor. The CVI inventory is a potential means of identifying and characterising the condition, which can be ameliorated with simple strategies.
Rimona S Weil - One of the best experts on this subject based on the ideXlab platform.
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Visual Dysfunction predicts cognitive impairment and white matter degeneration in parkinson s disease
Movement Disorders, 2021Co-Authors: Angeliki Zarkali, Peter Mccolgan, Louiseann Leyland, Andrew J Lees, Rimona S WeilAbstract:Background Visual Dysfunction predicts dementia in Parkinson's disease (PD), but whether this translates to structural change is not known. The objectives of this study were to identify longitudinal white matter changes in patients with Parkinson's disease and low Visual function and also in those who developed mild cognitive impairment. Methods We used fixel-based analysis to examine longitudinal white matter change in PD. Diffusion MRI and clinical assessments were performed in 77 patients at baseline (22 low Visual function/55 intact vision and 13 PD-mild cognitive impairment/51 normal cognition) and 25 controls and again after 18 months. We compared microstructural changes in fiber density, macrostructural changes in fiber bundle cross-section and combined fiber density and cross-section, across white matter, adjusting for age, sex, and intracranial volume. Results Patients with PD and Visual Dysfunction showed worse cognitive performance at follow-up and were more likely to develop mild cognitive impairment compared with those with normal vision (P = 0.008). Parkinson's with poor Visual function showed diffuse microstructural and macrostructural changes at baseline, whereas those with mild cognitive impairment showed fewer baseline changes. At follow-up, Parkinson's with low Visual function showed widespread macrostructural changes, involving the fronto-occipital fasciculi, external capsules, and middle cerebellar peduncles bilaterally. No longitudinal change was seen in those with mild cognitive impairment at baseline or converters, even when the 2 groups were combined. Conclusion Parkinson's patients with poor Visual function show increased white matter damage over time, providing further evidence for Visual function as a marker of imminent cognitive decline. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Visual Dysfunction predicts cognitive impairment and white matter degeneration in parkinson s disease
bioRxiv, 2020Co-Authors: Angeliki Zarkali, Peter Mccolgan, Louiseann Leyland, Andrew J Lees, Rimona S WeilAbstract:Visual Dysfunction predicts dementia in Parkinsons disease (PD), but whether this translates to structural change is not known. We aimed to identify longitudinal white matter changes in patients with Parkinsons disease and low Visual function and also in those who developed mild cognitive impairment (MCI). We used fixel-based analysis to examine longitudinal white matter change in PD. Diffusion MRI and clinical assessments were performed in 77 patients at baseline (22 low Visual function /55 intact vision; and 13 MCI, 13 MCI converters /51 normal cognition) and 25 controls and again after 18 months. We compared micro-structural changes in fibre density, macro-structural changes in fibre bundle cross-section (FC) and combined fibre density and cross-section across white matter, adjusting for age, gender and intracranial volume. Patients with Parkinsons and Visual Dysfunction showed worse cognitive performance at follow up and were more likely to develop MCI compared with those with normal vision (p=0.008). Parkinsons with poor Visual function showed diffuse micro-structural and macro-structural changes at baseline, whereas those with MCI showed fewer baseline changes. At follow-up, Parkinsons with low Visual function showed widespread macrostructural changes, involving the fronto-occipital fasciculi, external capsules, and middle cerebellar peduncles bilaterally. No longitudinal change was seen in baseline MCI or in MCI converters, even when the two groups were combined. Parkinsons patients with poor Visual function show increased white matter damage over time, providing further evidence for Visual function as a marker of imminent cognitive decline.
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fiber specific white matter reductions in parkinson hallucinations and Visual Dysfunction
Neurology, 2020Co-Authors: Angeliki Zarkali, Peter Mccolgan, Louiseann Leyland, Andrew J Lees, Geraint Rees, Rimona S WeilAbstract:Objective To investigate the microstructural and macrostructural white matter changes that accompany Visual hallucinations and low Visual performance in Parkinson disease, a risk factor for Parkinson dementia. Methods We performed fixel-based analysis, a novel technique that provides metrics of specific fiber-bundle populations within a voxel (or fixel). Diffusion MRI data were acquired from patients with Parkinson disease (n = 105, of whom 34 were low Visual performers and 19 were hallucinators) and age-matched controls (n = 35). We used whole-brain fixel-based analysis to compare microstructural differences in fiber density (FD), macrostructural differences in fiber bundle cross section (FC), and the combined FD and FC (FDC) metric across all white matter fixels. We then performed a tract-of-interest analysis comparing the most sensitive FDC metric across 11 tracts within the Visual system. Results Patients with Parkinson disease hallucinations exhibited macrostructural changes (reduced FC) within the splenium of the corpus callosum and the left posterior thalamic radiation compared to patients without hallucinations. While there were no significant changes in FD, we found large reductions in the combined FDC metric in Parkinson hallucinators within the splenium (>50% reduction compared to nonhallucinators). Patients with Parkinson disease and low Visual performance showed widespread microstructural and macrostructural changes within the genu and splenium of the corpus callosum, bilateral posterior thalamic radiations, and left inferior fronto-occipital fasciculus. Conclusions We demonstrate specific white matter tract degeneration affecting posterior thalamic tracts in patients with Parkinson disease with hallucinations and low Visual performance, providing direct mechanistic support for attentional models of Visual hallucinations.
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Visual Dysfunction in parkinson s disease
Brain, 2016Co-Authors: Andrew J Lees, Rimona S Weil, Jason D Warren, Sebastian J Crutch, Anette Schrag, Huw R MorrisAbstract:Patients with Parkinson's disease have a number of specific Visual disturbances. These include changes in colour vision and contrast sensitivity and difficulties with complex Visual tasks such as mental rotation and emotion recognition. We review changes in Visual function at each stage of Visual processing from retinal deficits, including contrast sensitivity and colour vision deficits to higher cortical processing impairments such as object and motion processing and neglect. We consider changes in Visual function in patients with common Parkinson's disease-associated genetic mutations including GBA and LRRK2 . We discuss the association between Visual deficits and clinical features of Parkinson's disease such as rapid eye movement sleep behavioural disorder and the postural instability and gait disorder phenotype. We review the link between abnormal Visual function and Visual hallucinations, considering current models for mechanisms of Visual hallucinations. Finally, we discuss the role of visuo-perceptual testing as a biomarker of disease and predictor of dementia in Parkinson's disease.
Kimberly P Cockerham - One of the best experts on this subject based on the ideXlab platform.
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automated perimetry and Visual Dysfunction in blast related traumatic brain injury
Ophthalmology, 2016Co-Authors: Sonne Lemke, Glenn C Cockerham, Catherine Glynnmilley, Richard C Lin, Kimberly P CockerhamAbstract:Purpose To evaluate feasibility and results of automated perimetry in veterans with combat blast neurotrauma. Design Prospective, longitudinal, observational case series. Participants Sixty-one patients in a Veterans Affairs Polytrauma Center diagnosed with traumatic brain injury (TBI) from combat blast exposure. Methods Study participants underwent automated perimetry at baseline (median interval, 2 months after injury) (Humphrey Field Analyzer, Carl Zeiss Meditec, Dublin, CA, Swedish Interactive Threshold Algorithm 30-2 Standard or Fast), and 36 of them were followed up (median interval, 10 months after baseline). Presence of significant mean deviation and pattern standard deviation was determined for testing with reliability indices ≤20% for fixation loss, 15% for false-positives, and 33% for false-negatives. Test–retest stability of global Visual field indices was assessed for tests with these cutoffs or with elevated fixation loss. Associations between global Visual field defects and predictors were examined. Main Outcome Measures Global Visual field indices (mean deviation and pattern standard deviation). Results Among 61 study participants (109 study eyes) with baseline testing, a field that met reliability cutoffs was obtained for 48 participants (79%) and 78 eyes (72%). Fixation loss was found in 29% of eyes in initial testing. Nine study participants (15%) demonstrated hemianopia or quadrantanopia, and an additional 36% had an abnormal global Visual field index. Global indices were relatively stable at follow-up testing for tests meeting fixation-loss cutoffs and tests that did not. Visual scotomas due to post-chiasmal lesions were associated with moderate to severe TBI or penetrating head injury, but other Visual field deficits were prevalent across the range of mild to severe TBI. Ocular injury to the retina or choroid, poorer Visual acuity, and pupillary defect were associated with Visual field defects. Participants with depressed Visual field sensitivity reported lower Visual quality of life. Conclusions Reliable automated perimetry can be accomplished in most patients with TBI from combat blast exposure and reveals high rates of Visual field deficits, indicating that blast forces may significantly affect the eye and Visual pathways.
Alistair J Barber - One of the best experts on this subject based on the ideXlab platform.
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deletion of the akt mtorc1 repressor redd1 prevents Visual Dysfunction in a rodent model of type 1 diabetes
Diabetes, 2018Co-Authors: William P Miller, Alistair J Barber, Chen Yang, Maria L Mihailescu, Joshua A Moore, Weiwei Dai, Michael D DennisAbstract:Diabetes-induced Visual Dysfunction is associated with significant neuroretinal cell death. The current study was designed to investigate the role of the Protein Regulated in Development and DNA Damage Response 1 (REDD1) in diabetes-induced retinal cell death and Visual Dysfunction. We recently demonstrated that REDD1 protein expression was elevated in response to hyperglycemia in the retina of diabetic rodents. REDD1 is an important regulator of Akt and mammalian target of rapamycin and as such plays a key role in neuronal function and survival. In R28 retinal cells in culture, hyperglycemic conditions enhanced REDD1 protein expression concomitant with caspase activation and cell death. By contrast, in REDD1-deficient R28 cells, neither hyperglycemic conditions nor the absence of insulin in culture medium were sufficient to promote cell death. In the retinas of streptozotocin-induced diabetic mice, retinal apoptosis was dramatically elevated compared with nondiabetic controls, whereas no difference was observed in diabetic and nondiabetic REDD1-deficient mice. Electroretinogram abnormalities observed in b-wave and oscillatory potentials of diabetic wild-type mice were also absent in REDD1-deficient mice. Moreover, diabetic wild-type mice exhibited functional deficiencies in Visual acuity and contrast sensitivity, whereas diabetic REDD1-deficient mice had no Visual Dysfunction. The results support a role for REDD1 in diabetes-induced retinal neurodegeneration.
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the translational repressor 4e bp1 contributes to diabetes induced Visual Dysfunction
Investigative Ophthalmology & Visual Science, 2016Co-Authors: William P Miller, Alistair J Barber, Chen Yang, Maria L Mihailescu, Scot R Kimball, Leonard S Jefferson, Michael D DennisAbstract:Purpose The translational repressor 4E-BP1 interacts with the mRNA cap-binding protein eIF4E and thereby promotes cap-independent translation of mRNAs encoding proteins that contribute to diabetic retinopathy. Interaction of 4E-BP1 with eIF4E is enhanced in the retina of diabetic rodents, at least in part, as a result of elevated 4E-BP1 protein expression. In the present study, we examined the role of 4E-BP1 in diabetes-induced Visual Dysfunction, as well as the mechanism whereby hyperglycemia promotes 4E-BP1 expression. Methods Nondiabetic and diabetic wild-type and 4E-BP1/2 knockout mice were evaluated for Visual function using a virtual optomotor test (Optomotry). Retinas were harvested from nondiabetic and type 1 diabetic mice and analyzed for protein abundance and posttranslational modifications. Similar analyses were performed on cells in culture exposed to hyperglycemic conditions or an O-GlcNAcase inhibitor (Thiamet G [TMG]). Results Diabetes-induced Visual Dysfunction was delayed in mice deficient of 4E-BP1/2 as compared to controls. 4E-BP1 protein expression was enhanced by hyperglycemia in the retina of diabetic rodents and by hyperglycemic conditions in retinal cells in culture. A similar elevation in 4E-BP1 expression was observed with TMG. The rate of 4E-BP1 degradation was significantly prolonged by either hyperglycemic conditions or TMG. A PEST motif in the C-terminus of 4E-BP1 regulated polyubiquitination, turnover, and binding of an E3 ubiquitin ligase complex containing CUL3. Conclusions The findings support a model whereby elevated 4E-BP1 expression observed in the retina of diabetic rodents is the result of O-GlcNAcylation of 4E-BP1 within its PEST motif.
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Visual Dysfunction associated with diabetic retinopathy
Current Diabetes Reports, 2010Co-Authors: Gregory R. Jackson, Alistair J BarberAbstract:Diabetic retinopathy is a leading cause of blindness and is commonly viewed as a vascular complication of diabetes mellitus. However, diabetes mellitus causes Visual Dysfunction before the onset of clinically visible microvascular changes associated with diabetic retinopathy. Thus, viewing diabetic retinopathy more generally as a neurovascular disease may lead to an improved understanding of the mechanisms responsible for vision loss. This article reviews the impact of diabetes mellitus on inner and outer retinal Visual and electrophysiologic function and advocates for a multimodal approach to the study of diabetic retinopathy.
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retinal ganglion cells in diabetes
The Journal of Physiology, 2008Co-Authors: Timothy S Kern, Alistair J BarberAbstract:Diabetic retinopathy has long been recognized as a vascular disease that develops in most patients, and it was believed that the Visual Dysfunction that develops in some diabetics was due to the vascular lesions used to characterize the disease. It is becoming increasingly clear that neuronal cells of the retina also are affected by diabetes, resulting in Dysfunction and even degeneration of some neuronal cells. Retinal ganglion cells (RGCs) are the best studied of the retinal neurons with respect to the effect of diabetes. Although investigations are providing new information about RGCs in diabetes, including therapies to inhibit the neurodegeneration, critical information about the function, anatomy and response properties of these cells is yet needed to understand the relationship between RGC changes and Visual Dysfunction in diabetes.
