| 1. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Intravitreal Injection of Triamcinolone Acetonide into Healthy Rabbit Eyes Alters Retinal Function and Morphology
- 2013
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 38:6, s. 649-661
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To study the effects of intravitreally injected triamcinolone acetonide (TA) and/or its preservative benzyl alcohol (BA) in healthy rabbit retina. Methods: Forty-eight rabbits (aged 4 months, body weight approximate to 3 kg) were randomized into four groups (n=12). They were examined with electroretinography (ERG) prior to drug exposure, and then injected intravitreally with a combination of TA and BA, TA without BA, BA alone or a balanced saline solution (BSS). The electroretinograms were assessed 1 week and 7 weeks post-injection. The rabbits were euthanized and the sectioned retinas were studied. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Muller cells. Results: Rabbits injected with BA showed a significantly lower rod-mediated b-wave amplitude than the controls 1 week after injection. TA-injected rabbits demonstrated significantly higher a- and b-wave amplitudes in the total retinal response than the controls 1 week post-injection. The rabbits injected with TA+BA demonstrated a significantly higher b-wave amplitude in the total retinal response than the controls 1 week after injection. The significantly higher a-wave amplitude in the total retinal response remained in the TA-injected rabbits 7 weeks after injection. Immunohistochemistry revealed that protein kinase C alpha (PKC alpha) was down-regulated in both the perikarya and the axons of bipolar cells in histological sections from rabbit retina injected with TA+BA, BA and TA. Conclusions: Intravitreal injection of the preservative BA reduces the isolated rod-mediated retinal response in the rabbit, transiently and selectively. Intravitreal injection of TA increases the total retinal response in the rabbit up to seven weeks after injection. The effects observed are not only limited to retinal function, but also include changes in the expression of PKC alpha in rod bipolar cells, indicating drug-related interference with normal retinal physiology in the healthy rabbit eye.
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| 2. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Retinal function and morphology in rabbit after intravitreal injection of VEGF inhibitors.
- 2012
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 37:5, s. 399-407
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Tidskriftsartikel (refereegranskat)abstract
- Purpose/Aim: To explore changes in morphology and function in the rabbit retina after intravitreal high-dose injection of three commonly used VEGF inhibitors. Materials and methods: Forty-eight rabbits of mixed strain (6 months of age, body weight ≈ 3 kg) were randomized into four groups (n = 12). They were examined with full-field electroretinography (ERG) and with multifocal electroretinography (mf ERG) prior to drug exposure. The rabbits were then injected intravitreally with bevacizumab, ranibizumab, pegaptanib, or with a balanced saline solution. The dose of VEGF inhibitor was chosen to achieve a vitreous concentration approximately three times higher than the one clinically used in the adult human eye. ERG was then performed 8 weeks postinjection, and mf ERG 9 weeks postinjection. After 9 weeks, the rabbits were sacrificed and the sectioned retina was studied. Immunohistochemical analysis was performed of rods, cones, rod bipolar cells, horizontal cells, and amacrine cells. Results: Rabbits injected with VEGF inhibitors all showed significantly lower amplitude of the dark-adapted b-wave rod-mediated response to dim light, compared to the rabbits injected with BSS. The a wave (reflecting photoreceptor function) in the response to single flash white light was however not affected. Immunohistochemistry revealed a significant reduction in PKC labeling of rod bipolar cells in pegaptanib and ranibizumab injected eyes whereas bevacizumab injected eyes displayed normal PKC labeling. No apparent morphological change was seen with markers for remaining retinal cells. Conclusions: Our results indicate that the use of high-dose intravitreal VEGF inhibitors in the rabbit eye affects rod-mediated retinal function and PKC expression in rod bipolars cells for at least 9 weeks after drug administration. The three VEGF inhibitors influence the retina slightly differently. These results are important for the understanding of drug action and when devising therapeutical strategies in new areas such as retinopathy of prematurity where vitreous volume is significantly lower compared to the adult eye.
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| 3. |
- Cardiakidis Myers, Anna, et al.
(författare)
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Retinal Function and Morphology in the Rabbit Eye after Intravitreal Injection of the TNF Alpha Inhibitor Adalimumab.
- 2014
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 39:11, s. 1106-1116
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Aim: To study the effects of the tumor necrosis factor alpha inhibitor adalimumab on rabbit retina after injection into the vitreous body. Methods: Forty-eight rabbits of mixed strain (9-12 months old, weighing ≈ 3.5 kg) were randomized into four groups. Adalimumab was injected at one of two concentrations (1.25 mg or 2.5 mg) into the eyes of two groups, and balanced salt solution into the eyes of the third group. The fourth group acted as controls. Full-field electroretinography (ffERG) was performed before injection and 1 and 6 weeks post-injection. At 6 weeks post-injection the rabbits were euthanized and the sectioned retinas were studied. Retinal histology was studied with hematoxylin-eosin staining. Immunohistochemical analysis was performed on rods, cones, rod bipolar cells, horizontal cells, amacrine cells and Müller cells. Results: No significant difference in ffERG amplitudes or implicit times was observed between the four groups at any time point. Histological and immunohistochemical findings were similar in all groups. Conclusions: Injection of adalimumab into the vitreous body of healthy rabbits, at doses up to 2.5 mg, does not appear to be toxic to the rabbit retina.
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| 4. |
- Carlsson, Stina K., et al.
(författare)
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Adenosine A2 receptor presence and synergy with cholinergic stimulation in rabbit lacrimal gland.
- 2010
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Ingår i: Current eye research. - : Informa UK Limited. - 1460-2202 .- 0271-3683. ; 35:6, s. 466-74
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Tidskriftsartikel (refereegranskat)abstract
- Secretion from the lacrimal gland is an important part of the well-being of the eye, and a central part in the search for treatment of dry eye syndrome. Adenosine has stimulatory effects on the lacrimal gland, and can potentiate the effect of the cholinergic agonist carbachol (Cch). The aim of the present study is to investigate the presence of the adenosine A(2) receptor subtypes A(2A) and A(2B) in the rabbit lacrimal gland, and to characterize their role in regulated acinar cell secretion.
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| 5. |
- Ghosh, Fredrik, et al.
(författare)
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Neuronal and Glial Alterations in Complex Long-Term Rhegmatogenous Retinal Detachment.
- 2012
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 37:8, s. 704-711
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To explore neuronal and glial alterations in eyes with complex long-term rhegmatogenous retinal detachment (RRD). Methods: Morphological analysis was performed on eight retinal specimens derived from patients treated with peripheral retinectomy for RRD complicated by retinal shortening or retinal thinning. All eyes had undergone previous surgeries including silicone oil tamponade, and had a median total detachment time of 2.5 months (range 2-12). Specimens were examined with hematoxylin and eosin staining and immunohistochemistry directed against activated Müller cells, ganglion cells, rod bipolar cells, and photoreceptors. Results: Retinal specimens displayed severe loss of photoreceptor and rod bipolar cells. Remaining neuronal cells exhibited disorganized perikarya and neurites with disruption of the normal retinal lamination. Müller cell activation was evident in all specimens with subretinal and epiretinal hypertrophy present in tissue derived from shortened retinal detachments. Conclusion: Long-term RRD leads to retinal remodeling characterized by loss of first and second order retinal neurons, disruption of the entire retinal lamination and gliosis. The severity of histopathological changes indicates that anatomical as well as functional recovery of the involved retina is precarious. The findings may be important when devising surgical strategies to avoid permanent retinal detachment.
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| 6. |
- Kronschläger, Martin, et al.
(författare)
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Evolution of TUNEL-labeling in the Rat Lens After In Vivo Exposure to Just Above Threshold Dose UVB
- 2013
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 38:8, s. 880-885
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Tidskriftsartikel (refereegranskat)abstract
- Purpose/Aim:To quantitatively analyse the evolution of TUNEL-labeling, after in vivo exposure to UVB.Methods:Altogether, 16 Sprague Dawley rats were unilaterally exposed in vivo for 15 min to close to threshold dose, 5 kJ/m(2), of ultraviolet radiation in the 300nm wavelength region. Animals were sacrificed in groups of 4 at 1, 5, 24 and 120 h after exposure. For each animal, both eye globes were removed and frozen. The frozen eye was cryo-sectioned in 10 mm thick midsagittal sections. From each globe, three midsagittal sections with at least five sections interval in between were mounted on a microscope slide. Sections were TUNEL-labeled and counter stained with DAPI. For quantification of apoptosis, a fluorescence microscope was used. In sections with a continuous epithelial cell surface, the number of lens epithelial cell nuclei and the number of TUNEL-positive epithelial cell nuclei was counted. The total number of TUNEL-positive epithelial cell nuclei for all three sections of one lens in relation to the total number of epithelial cell nuclei for all three sections of the same lens was compared between exposed and contralateral not exposed lens for each animal.Results:The relative difference of the fraction of TUNEL-positive nuclei between exposed and contralateral not exposed lens increased gradually, peaked in the time interval 5-120 h after exposure, and then declined.Conclusions:Close to threshold dose of UVB induces TUNEL-labeling that peaks in the time window 5-120 h after exposure to UVB.
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| 7. |
- Robciuc, A., et al.
(författare)
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Ceramides in the pathophysiology of the anterior segment of the eye
- 2013
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Ingår i: Current Eye Research. - : Informa Healthcare. - 0271-3683 .- 1460-2202. ; 38:10, s. 1006-1016
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Forskningsöversikt (refereegranskat)abstract
- Purpose: Sphingolipid (SL) research reached a peak in the past years. Yet this positive trend was not evident for eye research as the relative number of studies centered on SLs is decreasing. Our aim is to encourage the inclusion of SL metabolites in studies of ocular pathophysiology by summarizing recent findings and current awareness concerning ceramides in the anterior segment of the eye.Methods: Review of literature relating to ceramides as bioactive lipids and the extent to which their particular nature was investigated in ocular pathophysiology.Results: Ceramides are rare but indispensable lipids that influence cellular responses through their effects on membrane biophysical properties or direct interaction with target proteins. Their biological significance is increased by variability and adaptability as there are tens of enzymes designed to modulate their function. The eye offers a set of unique environments where ceramides or other SLs have not been extensively studied. Not surprisingly, ceramides were associated with apoptosis in the metabolically active tissues, while little is known about its effects on the biophysical properties of the tears or lens lipids. More so, there are still aspects of the ocular homeostasis control where SLs contribution has not been investigated to date (e. g. pathogen aggression).Conclusions: Ceramides and SL metabolism still receive increasing attention and have proven to be a significant metabolite in many research fields (e. g. cancer, stress response and inflammation) and there are yet many questions that they will aid answer. With the present work, we seek to increase awareness of these lipids also in eye research and to highlight their importance as common regulators of various diseases.
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| 8. |
- Taylor, Linnéa, et al.
(författare)
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Effects of Glial Cell Line-derived Neurotrophic Factor on the Cultured Adult Full-thickness Porcine Retina.
- 2013
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 38:4, s. 503-515
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: The tissue culture system offers a possibility to study factors involved in neuronal survival which may be important in a transplantation paradigm. The use of adult tissue in this setting poses specific challenges since traditionally mature neurons survive poorly in vitro. In the current paper, we have explored effects of glial cell line-derived neurotrophic factor (GDNF) on cultures of adult porcine retina. Methods: Full-thickness retinal sheets were isolated from adult porcine eyes and were cultured for 5 or 10 days under standard culture conditions with or without GDNF added to the culture medium. The grafts were analyzed morphologically using hematoxylin and eosin staining, immunohistochemistry and transferase dUTP nick end labeling (TUNEL) labeling. Retinas derived from normal adult porcine eyes were used as controls. Results: After 5 d in vitro (DIV), cultures without GDNF showed dissolving retinal lamination while specimens cultured with GDNF displayed the normal laminated morphology. At 10 DIV, the untreated cultures had been reduced to a degenerated cell mass, while the GDNF-cultured specimens retained thin but distinguishable retinal layers. TUNEL labeling confirmed these results. Immunohistochemical labelings and outer nuclear layer thickness measurements showed an increased preservation of photoreceptors and horizontal cells in the GDNF-treated group. Conclusions: The procedure of culturing retina involves several steps causing severe traumatic effects on the tissue, such as ganglion cell axotomy, interruption of the blood flow as well as separation from the retinal pigment epithelium (RPE). In this paper, we have shown that addition of GDNF in the culture medium attenuates the effect of these steps, resulting in enhanced preservation of several retinal neuronal subtypes. The results may be of importance for research in retinal transplantation where storage time of the donor tissue prior to transplantation is a critical issue.
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| 9. |
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| 10. |
- Strange, Michael
(författare)
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‘Act now and sign our joint statement!’ What role do online global group petitions play in transnational movement networks?
- 2011
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Ingår i: Media Culture and Society. - : Sage Publications. - 0163-4437 .- 1460-3675. ; 33:8, s. 1236-1253
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Tidskriftsartikel (refereegranskat)abstract
- The article focuses on a frequently used but under-researched protest medium through which transnational movement networks express their collective demands – what are termed here ‘global group petitions’ (GGPs), and activists themselves call ‘sign-on statements’ or ‘joint statements’. GGPs are online petitions typically framed as ‘global’ and linking sometimes hundreds of advocacy groups behind a common set of critical statements contesting global politics. Despite a burgeoning literature examining the use of digital media by movement networks, the article shows that GGPs are a distinct form of activism which to date has been overlooked by social science. Studying GGPs helps explore a series of issues central to understanding the role of advocacy groups in global politics, including their internal power relations (i.e. between North and South). Presenting empirical analysis and interviews with activists relating to five GGPs used in the course of a single transnational movement network – against negotiations to expand the World Trade Organization’s General Agreement on Trade-in-Services – the article concludes that whilst GGPs are not as ‘global’ or representative of a movement network as they may claim, their value is in facilitating momentum and a process of dialogue between potential advocacy partners.
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