bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stargardt macular dystrophy
Authors: HOLZ F , SCHMITZ‐VALCKENBERG S , CHARBEL ISSA P 
Published: August 2012

AbstractInitiation of a number of upcoming clinical trials for patients with Stargardt disease emphasizes the urge of determining objective outcome measures derived from retinal imaging. Especially novel techniques such as fundus autofluorescence (AF) and quantitative AF imaging as well as spectral domain optical coherence tomography (SD‐OCT) now allow assessing the characteristic pathology of Stargardt disease at different disease stages. Fundus AF highlights lipofuscin accumulation in the retinal pigment epithelium (RPE), the phenotypic finding that defines Stargardt disease. Also, fundus AF delineates areas of RPE atrophy with high contrast, allowing to longitudinally monitoring respective changes with high accuracy. SD‐OCT, on the other hand, is a clinically meaningful outcome measures since is allows to delineate the photoreceptor layer of the retina. Structural alterations within this layer have been shown to correlate directly with retinal function. Relevant functional parameters include visual acuity and microperimetry. Disease phenotyping (including comparison of various imaging modalities) as well as analysis of longitudinal imaging data, structure‐function‐correlations and genotype‐phenotype correlations will be prudent. In a prospective, multicenter, non‐interventional, non‐randomized, unmasked, observational study the natural history of patients with Stargardt’s disease will be characterized, prognostic markers identified and microstructural alterations and functional variations determined. Allö probands will be ABCA4‐genotyped.
Autophagy: a new way to retinal neuroprotection
Authors: RUSSO R , BAGETTA G , CORASANITI MT 
Published: August 2012

AbstractPurpose Autophagy is a highly conserved catabolic pathway in which proteins and organelles are engulfed by autophagic vacuoles (AVs) that are then targeted to lysosomes for degradation. Basal autophagy serves homeostatic function and it is induced during periods of cell stress. Defects in the autophagic machinery have been described in several neurodegenerative diseases. In this study we investigated the role of autophagy in the retinal neurodegeneration associated to ischemic conditions.Methods Retinal ischemia was induced in adult rats by acute elevation of intraocular pressure. Expression of autophagy related proteins, beclin‐1 and LC3, was studied by western blotting and immunofluorescence. NMDA antagonists, calpain inhibitors or siRNA were intravitreally administered. Effects of autophagy modulation on retinal ganglion cell (RGC) survival was evaluated in serum‐starved RGC‐5 treated with autophagy inhibitors or transfected with beclin‐1 siRNA.Results Beclin‐1 is part of the complex involved in the induction of autophagy, while LC3 plays an essential role in the expansion of AVs. Retinal ischemia produced a reduction of the autophagosome‐associated form of LC3 (LC3II) and induced a significant decrease of beclin‐1 expression. The latter event was dependent on NMDA receptors and calpain activation as shown by the prevention afforded by MK801, calpain inhibitors or calpain siRNA. Inhibition of autophagy or beclin‐1 silencing in RGC‐5 significantly reduced cell viability under serum starvation conditions.Conclusion Our results, while provide the first in vivo evidence of a calpain‐mediated cleavage of beclin‐I, show that retinal ischemia alters the dynamic of the autophagic process and suggest a neuroprotective role of autophagy in RGCs exposed to detrimental stimuli.
Neuroprotective factors against retinal injury in response to hypoxia: new perspectives
Authors: BAGNOLI P , DAL MONTE M 
Published: August 2012

AbstractPurpose In the retina, hypoxia is considered one of the key factors to trigger angiogenesis and to promote apoptosis by reducing photoreceptors and other retinal neurons, each of them contributing to vision loss. We recently demonstrated that the beta‐adrenergic system interferes with angiogenesis‐dependent diseases in the retina by regulating endogenous VEGF. Aim of the present study was to investigate the role of distinct beta‐adrenergic receptors (BARs)in neurodegenerative processes in response to hypoxia.Methods Ex vivo mouse retinal explants and in vivo models were used. BARs were blocked with antagonists or silenced with siRNAs. VEGFR2 was blocked with SU1498, whereas iNOs and eNOS with AG, L‐NIO or L‐NAME. mRNA levels were evaluated with quantitative RT‐PCR. BARs, iNOS, eNOS and apoptotic signals were determined with Western blot. Immunohistochemistry was used to localize BARs and to assess neovascularization. VEGF release and NO production were measured with colorimetric assays. Hoechst and TUNEL were used to evaluate cell loss.Results Among the BARs, BAR3 is localized to blood vessels, is upregulated by hypoxia and acts through iNOS/NO to control VEGF levels and degenerative responses to the hypoxic insult. In particular, BAR3 blockade is accompanied by increased levels of apoptotic signals and cell loss. Pharmacological interaction with the VEGF signalling demonstrates that BAR3 exerts a protective action on retinal cells through a modulation of endogenous VEGF.Conclusion Our findings demonstrate that modulation of BAR3 activity during ischemia may be a powerful means to achieve neuroprotection. VEGF's role in retinal cell survival has important implications for treatments with VEGF blockade within the context of ocular vascular diseases.
Retinal neuronal death caused by ocular hypertension
Authors: VIDAL‐SANZ M , SALINAS‐NAVARRO M , VALIENTE‐SORIANO FJ , ORTíN‐MARTíNEZ A , NADAL‐NICOLáS FM , ALARCóN‐MARTíNEZ L , AVILéS‐TRIGUEROS M , AGUDO‐BARRIUSO M , VILLEGAS‐PéREZ MP 
Published: August 2012

AbstractPurpose To characterize the anatomical and functional changes that follow ocular hypertension (OHT).Methods In adult albino rats or mice, the episcleral and perilimbar veins were photocauterized with laser diode. This resulted in OHT that reaches basal levels by one week in mice and by three weeks in rats.Results OHT induces anatomical and functional degenerative retinal changes. One week after lasering there is impairment of the retrograde axonal transport which is first functional and then mechanic. By two weeks there is loss of approximately 80% of the RGC population without further progression. RGCs loss occurs mainly in pie‐shaped sectors but is also diffuse throughout the retina. The intraretinal RGC axons and somas show signs compatible with a slow retrograde axonal degeneration resembling an optic nerve crush. OHT induces loss of RGCs but not of other non RGC neurons present in the ganglion cell layer, namely the displaced amacrine cells, for periods of up to six months after OHT. There is a protracted and progressive affectation of the outer retina which results in a major loss of LM‐ and S‐cones. This anatomical data are supported by functional analyses. Electroretinogram recordings show maintained and significant diminutions of the scotopic threshold responses as well as of the a‐ and b‐waves indicating permanent alterations of the inner and outer retinal layers, respectively.Conclusion OHT results both in RGC axonal crush‐like injury and in an ischemic damage to the outer retinal layers. Thus, this model may be used to study axotomy‐ or ischemia‐induced neuronal death in the innermost retina or in the outer retina, respectively.
RIP Kinases, necroptosis and redundancy in neuronal cell death
Authors: VAVVAS D , MURAKAMI Y , KAYAMA M , MILLER JW 
Published: August 2012

AbstractPurpose Neuronal cell death is the major cause of vision loss in many eye diseases. The exact mechanism remains unknown. Apoptosis has been thought to be the major form of regulated cell death and the main modality of neuronal cell death in degenerative ailments. However, neuroprotective strategies based on apoptosis have failed to materialize. We wanted to investigate the presence of alternative cell death modalities in various models of degenerative eye diseases.Methods Neuronal cell death was studied in a variety of animal models, including retinal detachment, RD10 juvenile degeneration, Cx3Cr1/CCL2/rd8 triple mutant, optic nerve crush, and chemical toxicity models (NMDA, PolyI:C, Na‐Iodate, Lipid peroxide, and chloroquine). Analysis of cell death was performed by transmission electron microscopy (TEM), TUNEL staining and standard molecular techniques.Results Caspase dependent apoptosis was the major cell death modality in most models of cell degeneration. However, RIP regulated necrosis accounted for a significant portion of cell death morphology. Under conditions of selective caspase inhibition, RIP regulated necrosis became the predominant cell death modality. Simultaneous caspase and RIPK inhibition lead to significant neuroprotection. Autophagy accounted for small portion of cell death in the models that it was examined.Conclusion RIP Kinase regulated necrosis (necroptosis) is a significant redundant cell death pathway in many animal models of ocular degenerative diseases. It becomes the predominant form of cell death under conditions of caspase inhibition. Combination treatments may be needed for successful neuroprotection.
Commercial interest
Neuroprotection and autoimmunity in glaucoma
Authors: GRUS F 
Published: August 2012

AbstractIn glaucoma, the elevated intraocular pressure cannot explain the disease in all patients. However, the pathogenesis of the disease is widely unknown. Biomarker research could be help to understand the disease process. Beside some genetic and proteomic biomarkers, immunoproteomics could play a significant role. Several studies could provide hints for an involvement of autoantibodies in the pathogenesis of the disease. The complex profiles of natural occurring autoantibodies were analyzed by Western Blotting and mass spectrometry based techniques combined with multivariate statistics and artificial neural networks. In several studies we could demonstrate consistent up‐ and down‐regulations of immune reactivities against ocular antigens in glaucoma patients. These findings could lead to a better understanding of the pathomechanisms involved in glaucoma, but could also lead to new innovative ways of early detection and neuroprotective treatment options of the disease.
Molecular pathology of inflammation in age‐related macular degeneration
Authors: CHAN C 
Published: August 2012

AbstractPurpose To review molecular pathology of inflammation in age‐related macular degenerationMethods Personal and collaborative research in addition to literature reviewResults Risk for AMD is multifactorial, relating to age, environmental and genetic factors. Genome‐wide and targeted genetic association studies have identified various polymorphisms important for AMD susceptibility. Many are within immune‐related genes, including complement factors, e.g. CFH, C2, C3, CFB, and CFI; Toll‐like receptors, e.g., TLR‐3 and TLR‐4; and chemokines and receptors, e.g., CX3CR1 and CCR3. In addition, copy number variation/polymorphism, miRNA and epigenetics related to immune relevant genes could also contribute to AMD pathogenesis and patient responses to specific therapies. Inflammatory cells (mainly macrophages and microglia) and inflammatory factors (complement factors, cytokines/chemokines, oxidative stress‐related inflammatory products) are demonstrated in AMD lesions at various stages.Conclusion The molecular characterization of AMD captures the localizations and interactions among the inflammatory elements, relevant molecules (e.g., oxidative stress products and lipoprotein), and retinal/choroidal cells, in particular, the photoreceptors and RPE.
Linking it together: structure‐function correlation
Authors: SUNARIC MEGEVAND G 
Published: August 2012

AbstractIn this part of the course we will discuss the implication of the combination of the structural and functional measurement. In glaucoma structural and functional measurements provide largely independent information, and most studies indicate that their agreement is generally poor. There is some evidence in the literature that structural damage may precede a correlative functional deterioration. However as concordance of measures is limited, combining longitudinal information from structural and functional tests can improve detection and assessment of glaucoma progression. New technological tools and statistical modeling approach combining structure and function may improve detection of progression today.
Strabismus surgery: minimally invasive or not?
Authors: MOJON D 
Published: August 2012

AbstractPurpose To present the advantages and disadvantages of minimally invasive strabismus surgery (miSS).Methods Review of available literature and experience from surgeons starting with MISS.Results MISS has the following advantages: less visibility of surgery, decrease of postoperative discomfort and pain, hospital stay and working disability, and preservation of limbal stem cells. Disadvantages of MISS are: long learning curve, need of microscope, difficulties visualizing anatomical variations, and increased risk of globe penetration.Conclusion For skilled surgeons with already experience in microscope assisted strabismus surgery transition to MISS will be easier.
Controversies related to mfVEP use
Authors: CASTELO‐BRANCO M , REIS A 
Published: August 2012

AbstractPurpose To address the usefulness of mfVEP use in clinical research on neurophthalmology, with a focus on optic neuropathies (Leber and Kjer Optic Neuropathies) as well as acquired cortical scotomas.Methods We have tested a sample of 17 asymptomatic Leber’s hereditary optic neuropathy (LHON) who were mtDNA 11778G>A mutation carriers from two generations of the same pedigree (mean age ± SD = 27.94 ± 12.97 years; mean visual acuity ± SD= 1.25 ± 0.11). We included an age‐matched control group (n=18; mean age ± SD = 33.29 ± 14.22 years; mean visual acuity ± SD= 1.09 ± 0.14). We have also studied 22 subjects (44 eyes) from 13 families with Autosomal Dominant Optic Atrophy (ADOA) submitted to OPA1 mutation analysis. Quantitative psychophysical methods were used to assess konio and parvocellular chromatic pathways. Electrophysiological assessment included the Multifocal Electroretinogram (mfERG) and Pattern Electroretinogram (PERG), respectively. Global Pattern and Multifocal VEP (visual evoked potentials) were used to assess retinocortical processing. Finally we performed multimodal studies (mfVEP and structural and functional MRI) to study visual loss in a patient with a cortical scotoma.Results We found evidence for functional impairment in color vision pathways in LOHN carriers, with relative preserved VEP and mfVEP responses. In ADOA mfVEP showed distinct evidence for cortical impairment that is only moderately explained by the retinal phenotype, suggesting additional damage mechanisms at the cortical level. fMRI based visual field cortical mapping revealed changes in retinotopic organization that were more difficult to identify using mfVEP.Conclusion mfVEP is an interesting tool in clinical research , but its application in the clinical diagnosis setting is still difficult.
Visual, ocular and refractive development in children
Authors: SCHAEFFEL F 
Published: August 2012

AbstractPurpose To describe visual, ocular and refractive development in children, possible reasons for deviations and some of the underlying mechanisms.Methods Literature review and own data.Results Contrast sensitivity and visual acuity develop slowly, reaching adult‐like performance around 5 years of age. Refractive development is very different if measured with and without cycloplegia but typically emmetropization was successful at 5 years of age, before the risk of myopia comes in. These developments require continuous visual feedback. If the retinal image is not focused or clouded by cataract, irreversible amblyopia develops. Eye growth represents by no means a linear scaling of the initial ocular dimensions. The decline in optical power of the cornea levels off already in the second year of life but axial eye growth continues at least until puberty. There is a built‐in risk factor for myopia because the crystalline lens has limited capacity to compensate for further axial elongation. These observations do not explain the environmental input to myopia development. In animal models, further axial eye growth is triggered by negative defocus, loss of image contrast, or abnormal light cycles or intensities. The retina is the major controller of axial eye growth. It uses image focus to control the growth of the underlying sclera bi‐directionally, depending on sign of defocus. Growth inhibition, induced by positive lenses, involves a biochemically different mechanism which is very responsive ‐ but can apparently still not save the human eye from myopic.Conclusion A lot can go wrong during postnatal ocular development since appropriate visual input is obligatory for normal development. Natural eye growth patterns include a built‐in risk factor for myopia development in early adolescence.
Myopia ‐ Its etiology and prevalence
Authors: SANKARIDURG P 
Published: August 2012

AbstractPurpose Myopia (short‐ sightedness) is a significant health problem that is fast rising in prevalence in many parts of world including Europe and USA and at a much higher percentage for population in parts of Asia. Also high myopia is associated with the risk of developing other sight threatening eye conditions.Methods An analysis of the published prevalence rates for myopia with the risks and morbidity associated with high levels of myopia. Also factors that are considered to play a role in the development and progression of the condition will be discussed with emphasis on published data for the role of these factors.Results Whilst the role of individual factors is yet to be elucidated both environmental and genetic factors have been considered to play a role. An increased prevalence of myopia in urban versus rural populations, association with outdoor/indoor work, supports and provides evidence for the role of environment. In this regard, many of the previous efforts have focussed on accommodative effort and blur at the central retina during near visual tasks. More recent evidence suggests that the peripheral retina also plays a role in emmetropisation and development of refractive errors.Conclusion This presentation will discuss the rates and differences in the prevalence of myopia across various populations. In addition, current hypotheses considering the aetiology of development and progression of myopia will be discussed.
Commercial interest
(New) Approaches to reduce progression of myopia with spectacles from Carl Zeiss Vision
Authors: KRATZER T 
Published: August 2012

AbstractPurpose This talk will present a dedicated spectacle lens design that has indicated to reduce the progression of myopia in a group of Asian children in a randomized and double blind clinical study.Methods In contrast to conventional spectacles lenses for myopes, the ZEISS MyoVision lens uses a special peripheral treatment zone to bring the peripheral focus back or in front of the retina while providing a clear and undisturbed asymmetric central vision. A clinical trial has been conducted to evaluate the performance of this new lens design.Results The combination of a peripheral treatment zone and a clear central viewing zone in a single vision lens show positive results by indicating a reduction of the progression of myopia by 30% on average in Asian children age 6‐12years old with a history of parental myopia while providing stable and clear vision without adaption problems of the wearer.Conclusion This lens has been successfully trialed in a randomized and double blind clinical study on Chinese school children. Modern spectacle lens designs with special treatment zones can lead to a reduction of the progression of myopia.
Commercial interest
A comparison of HLA genotype with inflammation in uveal melanoma
Authors: JAGER MJ , VAN ESSEN TH , BRONKHORST IHG , VERDUYN W , ROELEN DL , MAAT W , LUYTEN GPM 
Published: August 2012

AbstractPurpose HLA (Human Leukocyte Antigen) polymorphisms have been associated with the development of autoimmune diseases. In uveal melanoma, a high expression of HLA class I and II and infiltration with lymphocytes and macrophages are associated with a bad prognosis, and Natural Killer cells are thought to play a role in the killing of metastasizing cells. The goal of this study is to determine whether specific HLA alleles are associated with increased inflammation.Methods Records were analyzed of 45 patients who underwent enucleation for uveal melanoma. HLA typing, tumor HLA expression and tumor macrophage infiltration were determined in each case.Results Before correction for multiple testing, macrophage infiltration was less in HLA‐A2 positive patients. Patients with HLA‐DR6 had a higher tumor cell expression of HLA‐DR. After correction for the number of analyses, no associations remained statistically significant.Conclusion The results before correction suggest that the HLA genotype may influence inflammation as indicated by HLA expression and macrophage infiltration in uveal melanoma. Comparing HLA expression with the genetic presence of specific HLA alleles is a new approach to obtain insight into the role of the immune system in uveal melanoma.
Pre‐clinical analysis of Crizotinib in uveal melanoma
Authors: DE LANGE MJ , VERSLUIS M , JAGER MJ , LUYTEN GPM , VAN DER VELDEN PA 
Published: August 2012

AbstractPurpose Uveal melanoma (UM) is an intraocular neoplasm with an annual incidence of 7 per million. UM originates from melanocytes just like cutaneous melanoma (CM) and similar to CM, the MAPK pathway is involved in the development of UM. However, not all UM seem to depend on the activation of this pathway. Loss of ERK signalling may be correlated with progression as the ERK negative cells are derived from UM metastasis. Here, tumours apparently use different mechanisms to proliferate and survive. In this study, we aimed to determine the pathway that is up‐regulated in UM metastases and to inhibit its function with targeted kinase inhibitors.Methods We used pathway profiling to identify the pathways that are important in metastases. Furthermore, the c‐Met inhibitor (Crizotinib) was used to inhibit the c‐Met receptor and to identify downstream targets. Colony formation assays and 3D sphere assays were used to characterize UM cells in a three dimensional environment.Results Reduced c‐Met activation rather than reduced expression was induced with Crizotinib treatment. Subsequently, c‐Met inhibition was correlated with reduced colony formation. c‐Met positive UM cells captured in 3D spheres revealed a reduced capacity to migrate upon Crizotinib treatment compared to cells that lack activated c‐Met.Conclusion c‐Met activation was observed in metastasizing UM where it serves as biomarker for Crizotinib treatment. Efficacy of treatment was shown by inhibition of growth and migration. Combined our data reveals c‐Met signalling in progression of UM and support the use of Crizotinib for UM metastasis.