| 1. |
- Kronschläger, Martin, et al.
(författare)
-
Pharmacokinetics for topically applied caffeine in the rat
- 2014
-
Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 122, s. 94-101
-
Tidskriftsartikel (refereegranskat)abstract
- Topically applied caffeine was recently identified as a promising candidate molecule for cataract prevention. Little is known about the pharmacokinetics for topically applied caffeine. Potential toxicity of 72 mM caffeine on the ocular surface and the lens was qualitatively monitored and no toxic effects were observed. The concentration of caffeine was measured in the lens and the blood after topical application of 72 mM caffeine to groups of 10 animals sacrificed at 30, 60, 90 and 120 min after topical application. The lens concentration decreased throughout the observation period while the blood concentration increased up to 120 min. Further, the concentration of caffeine in the lens and blood was measured 30 min after topical application of caffeine, the concentration of caffeine being 0.72, 3.34, 15.51 and 72 mM depending on group belonging, in groups of 10 animals. The caffeine concentration in lens and blood, respectively, increased proportionally to the caffeine concentration topically applied. The rat blood concentrations achieved were far below the equivalent threshold dose of FDA recommended daily dose for humans. This information is important for further development of caffeine eye drops for cataract prevention.
|
|
| 2. |
- Kronschläger, Martin
(författare)
-
Prevention of Experimental Cataract Induced by UVR
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cataract is the leading cause of blindness in the world and is defined by opacification of the normally transparent lens of the eye. The major avoidable cause of cataract is ultraviolet radiation (UVR), but no current strategies have been developed to prevent the onset of cataract. Apoptosis and internal and external antioxidant systems that inhibit apoptosis have been shown to play a significant role in cataractogenesis.The main purposes of this thesis were to study the time evolution of apoptosis, to develop the concept of a protection factor (PF), and to investigate the effect of thioltransferase (Grx1) and topical caffeine in UVR cataract development. Further, to elucidate pharmacokinetics and influence on iris diameter of topical caffeine.Sprague Dawley rats were exposed to UVR and TUNEL staining of the lens sections was analysed. Grx1+/+ and Grx1-/- mice were exposed to 5 sub-doses of UVR. Based on the difference of light scattering between Grx1+/+ and Grx1-/- mice, the concept of the PF was developed. Topical caffeine and a placebo were applied to the eyes of separate groups of Sprague Dawley rats that were exposed to sub-doses of UVR and protective effect was evaluated. Penetration of topical caffeine in Sprague Dawley rats to lens and blood was analysed by high performance liquid chromatography. Pupil diameter was measured in groups of unilaterally and bilaterally caffeine-treated ketamine/xylazine anesthetized Sprague Dawley rats.TUNEL-labeling peaked between 5 and 120 hours after UVR exposure. The PF of Grx1 was 1.3. Moreover, topically administered caffeine protected against UVR-induced cataract development with a PF of 1.23. Topical caffeine peaked at 30 min in the lens, increased up to 120 min in the blood and antagonized ketamine/xylazine-induced mydriasis.In conclusion, UVR induces apoptosis, which is evidenced by the peak of TUNEL-labeling at 24 hours after UVR exposure. The PF is an objective relative measure of protective properties that allows the comparison of different antioxidant systems and administered antioxidant substances. Grx1 and caffeine are protective against UVR-induced cataract. Topically administered caffeine penetrates to the lens and inhibits UVR-induced apoptosis. Additionally, a miotic effect of caffeine is described for the first time.
|
|
| 3. |
- Kronschläger, Martin, et al.
(författare)
-
Topically applied caffeine induces miosis in the ketamine/xylazine anesthetized rat
- 2014
-
Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835 .- 1096-0007. ; 127, s. 179-183
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to examine if topically applied caffeine influences pupil size in ketamine/xylazine anesthetized animals. Two experiments were carried out. In the first experiment, caffeine was topically applied to one of the eyes of 10 ketamine/xylazine anesthetized animals, while vehicle only was topically applied to the contralateral eye. In the second experiment, caffeine was topically applied to both eyes in one group of 10 ketamine/xylazine anesthetized rats, while in another group both eyes vehicle only was topically applied to both eyes. In both experiments pupil diameter was measured at 0, 10, 20, 40 and 60 min after topical application. In three of the animals, the pupil was dilated with tropicamide 5 mg/ml at 60 min after the topical application of caffeine and the pupil diameter was measured. The first experiment showed a relative miosis in caffeine treated eyes as compared to the vehicle treated eye, that changed over time. The second experiment in line with the first experiment, also showed that topically applied caffeine causes a relative miosis as compared to vehicle only that changes over time. Eyes treated with caffeine reacted with quick dilatation after tropicamide application. Topical caffeine antagonizes ketamine/xylazine anesthesia induced mydriasis in a time dependent manner.
|
|
| 4. |
- Meyer, L. M., et al.
(författare)
-
Schleimpflug photography detects alterations in corneal density and thickness in patients with dry eye disease
- 2014
-
Ingår i: Der Ophthalmologe. - : Springer Science and Business Media LLC. - 0941-293X .- 1433-0423. ; 111:10, s. 914-919
-
Tidskriftsartikel (refereegranskat)abstract
- Dry eye disease is a common ocular surface disease that significantly affects the quality of life. Little is known about a potential impact of the disease on corneal morphology. This study was carried out to investigate for the first time if dry eye disease induces changes in corneal density and thickness. In total 97 patients suffering from dry eye disease and 33 healthy age-matched individuals were included in this prospective, randomized study. Corneal morphology was documented with Scheimpflug photography and analyzed for central corneal thickness and corneal density in five anatomical layers (i.e. epithelium, Bowman membrane, corneal stroma, Descemet membrane and endothelium). Corneal density was significantly reduced in the epithelium (p = 0.0053), Bowman membrane (p = 0.0049) and Descemet's membrane (p = 0.0385) in patients with dry eye syndrome compared to healthy controls. This decrease was age-dependant. Furthermore, central corneal thickness was significantly reduced in patients with dry eye syndrome compared to the control group (p = 0.0495). The change was again dependent on age with lower values at higher age. Central corneal thickness increased with age in the control group. The results of this study indicate that corneal morphology is subject to significant alterations in patients with dry eye disease. Scheimpflug photography provides not only unique information in lens trials but is also able to detect changes of corneal anatomy. However, further investigations with other anterior segment imaging techniques, such spectral domain optical coherence tomography (SD OCT/PentacamA (R)) are necessary to further evaluate the clinical consequences of these findings.
|
|
| 5. |
- Meyer, Linda, et al.
(författare)
-
Ultrastructure of UVR-B-induced cataract and repair visualized with electron microscopy
- 2014
-
Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 92:7, s. 635-643
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeThe aim of the study is to investigate and visualize the ultrastructure of cataract morphology and repair, after in vivo exposure to double threshold dose UVR-B in the C57BL/6 mouse lens.MethodsTwenty-six-week-old C57BL/6 mice received in vivo double threshold dose (6.4 kJ/m2) UVR-B for 15 min. The radiation output of the UVR-source had λMAX at 302.6 nm. After a latency period of 1, 2, 4 and 8 days following UVR-B exposure, the induced cataract was visualized with electron microscopy techniques. Induced, cataract was quantified as forward lens light scattering. Damage to the lens epithelium and the anterior cortex was investigated with light microscopy in toluidine blue-stained semi-thin sections, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and dark field illumination photography.ResultsUVR-B-exposed lenses developed anterior subcapsular and/or cortical and nuclear cataract after 1 day. Lens light scattering peaked 2 days after exposure. Lens epithelial cell damage was seen in TEM as apoptotic cells, apoptotic bodies, nuclear chromatin condensation, and swollen and disrupted anterior cortex fibres throughout the sections of the whole anterior lens surface. These morphologic changes were also visualized with SEM. Within 8 days, anterior subcapsular cataract was repaired towards the anterior sutures.ConclusionUVR-B exposure of double cataract threshold dose induces a subtotal loss of epithelial cells across the whole anterior surface of the lens. This damage to the epithelium is repaired by epithelial cell movement from the equator towards the lens sutures, thus in retrograde direction to regular epithelial cell differentiation.
|
|
| 6. |
- Talebizadeh, Nooshin, 1977-, et al.
(författare)
-
Modelling the time evolution of active caspase-3 protein in the rat lens after in vivo exposure to Ultraviolet radiation-B : Model for active caspase-3 expression after in vivo exposure to UVR-300 nm
- 2014
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:9, s. e106926-
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: To introduce a model for the time evolution of active caspase-3 protein expression in albino rat lens up to 24 hours after in vivo exposure to low dose UVR in the 300 nm wavelength region (UVR-300 nm).Methods: Forty Sprague-Dawley rats were unilaterally exposed in vivo to 1 kJ/m2 UVR-300 nm for 15 minutes. At 0.5, 8, 16, and 24 hours after the UVR exposure, the exposed and contralateral not-exposed lenses were removed and processed for immunohistochemistry. The differences in the probability of active caspase-3 expression at four different time points after exposure were used to determine the time evolution of active caspase-3 expression. A logistic model was introduced for the expression of active caspase-3. The parameters for the exposed and the not exposed lenses were estimated for the observation time points.Results: The exposure to UVR-300 nm impacted on the parameters of the logistic model. Further, the parameters of the model varied with time after exposure to UVR-300 nm.Conclusion: The logistic model predicts the impact of exposure to UVR-300 nm on the spatial distribution of probability of active caspase-3 protein expression, depending on time.
|
|
| 7. |
- Talebizadeh, Nooshin, 1977-, et al.
(författare)
-
Specific spatial distribution of caspase-3 in normal lenses
- 2014
-
Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 93:3, s. 289-292
-
Tidskriftsartikel (refereegranskat)abstract
- PurposeTo determine the distribution of active caspase-3 in rat eye lens epithelium.MethodsIn total, 120 sagittal sections from forty rats were assessed for active caspase-3 labelling using immunohistochemistry. Lens epithelial cells were counted, and the fraction of active caspase-3 labelled cells and their relative positions were identified in each section.ResultsActive caspase-3 is present in normal lens epithelium. The active caspase-3 expression was higher in the anterior pole of the lens. Probability of radial spatial distribution of labelling was fitted with a logistic model. The increase rate and the inflection point were estimated as CI (0.95) to 23 ± 3 cells and 114 ± 3 cells, respectively.ConclusionThe gradually decreasing active caspase-3 labelling from the anterior pole to the periphery suggests that active caspase-3 may be involved in normal protein turnover caused by, for example, incident light.
|
|
| 8. |
- Talebizadeh, Nooshin, et al.
(författare)
-
Time evolution of active caspase-3 labelling after in vivo exposure to UVR-300 nm
- 2014
-
Ingår i: Acta Ophthalmologica. - : Wiley. - 1755-375X .- 1755-3768. ; 92:8, s. 769-773
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE:To determine the time evolution of active caspase-3 protein expression in albino rat lens after in vivo exposure to low-dose UVR-300 nm, as detected by immunofluorescence.METHODS:Forty Sprague-Dawley rats were unilaterally exposed in vivo to 1 kJ/m2 UVR-300 nm for 15 min. At 0.5, 8, 16 and 24 hr after the UVR exposure, the exposed and contralateral nonexposed lenses were removed and processed for immunohistochemistry. Three mid-sagittal sections from each lens were stained. The cells labelled for active caspase-3 in each section of both the exposed and nonexposed lenses were counted and recorded three times. The difference of the proportion of labelling between the exposed and contralateral nonexposed lenses within each animal was calculated. The differences of active caspase-3 labelling at four different time-points after exposure were used to determine the time evolution of active caspase-3 expression.RESULTS:Caspase-3 expression was higher in the exposed than in contralateral nonexposed lenses. The mean difference between the exposed and contralateral nonexposed lenses, including all lenses from all time intervals, was 0.12 ± 0.01 (= CI 95%). The mean differences between the exposed and contralateral nonexposed lenses were 0.11 ± 0.02, 0.13 ± 0.02, 0.14 ± 0.01 and 0.09 ± 0.03 (= CI 95%) for the 0.5-, 8-, 16- and 24-hr time groups, respectively. The orthogonal comparison showed no difference in the expression of active caspase-3 between the 0.5- and the 24-hr groups (Test statistic 1.50, F1,36 = 4.11, p < 0.05) or between the 8- and the 16-hr groups (test statistic 0.05, F1,36 = 4.11, p < 0.05). There was a difference when comparing the 0.5- and 24-hr groups to the 8- and 16-hr groups (test statistic 7.01, F1,36 = 4.11, p < 0.05).CONCLUSION:The expression of active caspase-3 in the lens epithelium increases after UVR exposure. There is a peak of expression approximately 16 hr after the exposure.
|
|
| 9. |
- Yu, Zhaohua, 1983-, et al.
(författare)
-
Ocular temperature elevation induced by threshold in vivo exposure to 1090 nm infrared radiation and associated heat diffusion
- 2014
-
Ingår i: Journal of Biomedical Optics. - 1083-3668 .- 1560-2281. ; 19:10, s. 105008-
-
Tidskriftsartikel (refereegranskat)abstract
- An in vivo exposure to 197 W/cm2 1090 nm infrared radiation (IRR) requires a minimum 8 s for cataract induction. The present study aims to determine the ocular temperature evolution and the associated heat flow at the same exposure conditions. Two groups of 12 rats were unilaterally exposed within the dilated pupil with a close to collimated beam between lens and retina. Temperature was recorded with thermocouples. Within 5 min after exposure, the lens light scattering was measured. In one group, the temperature rise in the exposed eye, expressed as CI(0.95), was 11±3 ºC at the limbus, 16±6 ºC in the vitreous behind lens and 16±7 ºC on the sclera next to the optic nerve, respectively. In the other group, the temperature rise in the exposed eye was 9±1 ºC at the limbus and 26±11 ºC on the sclera next to the optic nerve, respectively. The difference of forward light scattering between exposed and contralateral not exposed eye was 0.01±0.09 tEDC. An exposure to 197 W/cm2 1090 nm IRR for 8 s induces a temperature increase of 10 °C at the limbus and 26 °C close to the retina. IRR cataract is probably of thermal origin.
|
|
