| 1. |
- Agardh, Elisabet, et al.
(författare)
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Effects of inhibition of glycation and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats
- 2000
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Ingår i: Current Eye Research. - 0271-3683. ; 21:1, s. 543-549
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study effects of inhibition of glycation, and oxidative stress on the development of cataract and retinal vessel abnormalities in diabetic rats. METHODS: Diabetes was induced in male Wistar rats with streptozocin (STZ; 60 mg/kg BW, i.p.). Diabetic as well as strain matched control rats were fed 1) a normal diet, 2) addition of aminoguanidine in the drinking water (0.5 g/l for diabetic rats and 1.0 g/l for control rats) or 3) probucol in the pellets (1% w/w). After 6 months, the number of acellular vessels, endothelial cells and pericytes were counted in trypsin digested retinal vessel preparations, and the total retinal tissue amount of glutathione (GSH) and cysteine was measured with HPLC. RESULTS: Cataract formation occurred after 13 weeks in diabetic animals compared with 17 weeks for those treated with aminoguanidine, and 16 weeks for those treated with probucol (p < 0.001 in both cases). Aminoguanidine inhibited the formation of acellular collapsed capillary strands, 9 (3-14) vs. 18 (12-262) (median, range) per quadrant in untreated diabetic rats (p = 0.004), while probucol did not have any effect. Neither aminoguanidine, nor probucol influenced the endothelial/pericyte ratio. Diabetes caused a reduction in the GSH/cysteine ratio (10.7 +/- 0.6 vs. 15.3 +/- 1. 5) (mean +/- SD; p < 0.001). Probucol partly restored this imbalance (p < 0.05) whereas aminoguanidine did not. CONCLUSIONS: The results indicate that cataract formation in diabetes involves both glycation and oxidative stress processes. The reduced formation of acellular collapsed capillary strands by aminoguanidine suggests a potential role for glycation in vascular damage. The positive effect of probucol on cysteine/GSH metabolism imbalance indicates that derangements of one of the retinal defense systems against oxidative stress can be normalized by antioxidants.
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| 2. |
- Agardh, Carl-David, et al.
(författare)
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The glutathione levels are reduced in Goto-Kakizaki rat retina, but are not influenced by aminoguanidine treatment
- 1998
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 17:3, s. 251-256
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To examine the levels of the free radical protecting enzyme glutathione and the endothelial/pericyte ratio in retinal capillaries in the Goto-Kakizaki (GK) Wistar rat, with and without aminoguanidine treatment. METHODS: Eight-month-old GK rats, with non-obese, spontaneous non-insulin-dependent diabetes mellitus (NIDDM), were examined after a six month period of aminoguanidine treatment. Glutathione levels were measured with high performance liquid chromatography and the endothelial/pericyte ratio was calculated in trypsin digested vessel preparations. RESULTS: The levels of glutathione in GK rat retina were significantly lower compared to controls (p = 0.0108). There was no difference in the endothelial/pericyte ratio compared to matched control rats (1.8 +/- 0.2 vs. 1.8 +/- 0.1, respectively). Aminoguanidine treatment did not influence either the degree of hyperglycemia, the levels of glutathione or the endothelial/pericyte ratio in GK or control rat retina. CONCLUSIONS: The results indicate that impaired glucose metabolism may influence one of the defense mechanisms for oxidative stress, but also suggest that decreased glutathione levels occur prior to morphological signs of pericyte loss and/or endothelial cell proliferation in this animal model of hereditary NIDDM.
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| 3. |
- Agardh, Elisabet, et al.
(författare)
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Retinal glial cell immunoreactivity and neuronal cell changes in rats with STZ-induced diabetes
- 2001
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 23:4, s. 276-284
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study whether diabetes could influence glial cells, retinal neurons, and pigment epithelial cells and if so, to evaluate whether any changes could be influenced by aminoguanidine (AG) or probucol (PB). METHODS: Streptozocin (STZ)-induced diabetic male Wistar rats and age-matched control rats were fed a normal diet, addition of AG in the drinking water (0.5 g/l for diabetic and 1.0 g/l for control rats) or PB in the pellets (1 % w/w) for one or six months. Paraffin embedded retinal sections were incubated in the primary antibodies GFAP, calbindin, RPE65, and Hu, for glial, horizontal, pigment epithelial, and ganglion cells, respectively, and in fluorescent secondary antibodies. RESULTS: One month after STZ injection, GFAP immunoreactivity was sparse, but after six months it was prominent in glial cells in 5/5 diabetic and 1/7 control retinas (p = 0.015). Neither AG, nor PB influenced this immunoreactivity. Numbers of retinal pigment epithelial cells and cells in the ganglion cell layer, were similar at one and six months of diabetes. By time, the number of horizontal cells decreased (p < 0.001) and branching and numbers of their terminals were reduced (p < 0.001). CONCLUSION: Diabetes for six months resulted in increased glial cell immunoreactivity, and by age, horizontal cell numbers and branching of their terminals decreased, morphological patterns that were unaffected by AG or PB. The numbers of retinal pigment epithelial cells and cells in the ganglion cell layer were unaffected both by age and diabetes.
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| 4. |
- Barth, Henrik, et al.
(författare)
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A New Retinal Detachment Treatment Model for Evaluation of Vitreous Tamponades
- 2021
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Ingår i: Current Eye Research. - : Taylor & Francis. - 0271-3683 .- 1460-2202. ; 46:3, s. 373-379
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To develop a treatment model of rhegmatogenous retinal detachment (RRD) in which the effects of various vitreous tamponades can be explored.METHODS: In a primary session, detachment was produced in the right eye of 24 rabbits using vitrectomy, posterior vitreous detachment, retinal break induction, and subretinal injection of viscoelastic solution. The following day, detachments were treated in 16 eyes using SF6 (n = 8) or Healaflow® (HF, a cross-linked hyaluronic acid hydrogel, n = 8) tamponade. Animals were followed for 1 month and thereafter examined macroscopically and morphologically in hematoxylin and eosin-stained sections.RESULTS: Retinal detachment (RD) was successfully treated using repeated surgery. Two HF eyes developed progressive vitritis and were excluded from further evaluation. Enlargement of the initial retinal rupture with concomitant RD was seen in 4/8 SF6 eyes, while all 6 HF eyes displayed an attached retina. Attached areas showed a normal retinal morphology except for in 1 HF eye with extensive degeneration.CONCLUSIONS: The RRD repeat vitrectomy model offers a possibility to explore the efficacy and complications of novel potential vitreous tamponades. Gel-based Healaflow® displays excellent anatomic reattachment, however, vitritis and retinal degeneration in some cases warrants further investigation.
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| 5. |
- Björkblom, Benny, et al.
(författare)
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Xenobiotic- and Serum-Free Culture of Oral Mucosal Epithelial Cells on Contact Lenses
- 2016
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Ingår i: Current Eye Research. - : Informa UK Limited. - 0271-3683 .- 1460-2202. ; 41:1, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- Purpose/aim: Cultured autologous oral mucosal epithelial cells (OMECs) have proven useful in the treatment of ocular surface disorders. This study is the first to investigate the potential of expanding OMEC in a xenobiotic- and serum-free medium using therapeutic contact lenses (CLs) as a substrate and carrier.Materials and methods: Porcine OMEC were seeded on laminin-coated lotrafilcon A therapeutic CLs with the density of 8x10(4)cells/lens and cultured in a defined serum and xenobiotic-free medium. Confocal immunofluorescence microscopy was used to analyze the following: (1) cellular morphology by using rhodamine-phalloidin staining of F-actin, (2) phenotype by applying antibodies against the progenitor cell marker p63 and the putative stem cell marker ABCG2 and (3) cell viability by using propidium iodide and Hoechst 33342 dual staining.Results: Porcine OMEC attached well to the CLs, and cell-to-cell contacts were evident. After three days in culture, the OMEC displayed a confluent monolayer with uniform cobblestone morphology, whereas stratified cultures with 2-3 layers were formed after six days. No significant difference in expression of p63 was observed after three-day culture (79.414.8%) compared with six-day culture (60.3 +/- 18.9%). ABCG2 expression in the basal cell layer was 6.3 +/- 1.0% and 4.8 +/- 1.8% after three- and six-day culture, respectively. The basal layer viability of cultured OMECs was 99.3 +/- 0.2% and 82.8 +/- 1.1% after three and six days culture, respectively.Conclusions: The use of therapeutic CLs has potential as a substrate and carrier for OMEC cultured in a xenobiotic- and serum-free culture system.
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| 6. |
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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
- 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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