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Topically applied caffeine induces miosis in the ketamine/xylazine anesthetized rat
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
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2014 (English)In: Experimental Eye Research, ISSN 0014-4835, E-ISSN 1096-0007, Vol. 127, 179-183 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2014. Vol. 127, 179-183 p.
National Category
Ophthalmology
Identifiers
URN: urn:nbn:se:uu:diva-229926DOI: 10.1016/j.exer.2014.07.023ISI: 000342539900021OAI: oai:DiVA.org:uu-229926DiVA: diva2:738306
Available from: 2014-08-18 Created: 2014-08-18 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Prevention of Experimental Cataract Induced by UVR
Open this publication in new window or tab >>Prevention of Experimental Cataract Induced by UVR
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Uppsala universitet, 2014. 44 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1036
Keyword
cataract, ultraviolet radiation, apoptosis, thioltransferase, caffeine
National Category
Ophthalmology
Identifiers
urn:nbn:se:uu:diva-232955 (URN)978-91-554-9055-3 (ISBN)
Public defence
2014-11-28, Enghoffsalen, Ing. 50, plan 1., Akademiska Sjukhuset, Uppsala, 13:00 (English)
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Available from: 2014-11-06 Created: 2014-09-28 Last updated: 2015-01-23

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Kronschläger, MartinYu, ZhaohuaTalebizadeh, NooshinSöderberg, Per

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