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MEK/ERK/1/2 sensiti...
MEK/ERK/1/2 sensitive vascular changes coincide with retinal functional deficit, following transient ophthalmic artery occlusion
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- Blixt, Frank W. (författare)
- Lund University,Lunds universitet,Experimentell kärlforskning,Forskargrupper vid Lunds universitet,Experimental Vascular Research,Lund University Research Groups
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- Haanes, Kristian Agmund (författare)
- Copenhagen University Hospital
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- Ohlsson, Lena (författare)
- Lund University,Lunds universitet,Experimentell kärlforskning,Forskargrupper vid Lunds universitet,Experimental Vascular Research,Lund University Research Groups
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- Dreisig, Karin (författare)
- Copenhagen University Hospital
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- Fedulov, Vadim (författare)
- Copenhagen University Hospital
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- Warfvinge, Karin (författare)
- Lund University,Lunds universitet,Medicin/akutsjukvård, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine,Copenhagen University Hospital
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- Edvinsson, Lars (författare)
- Lund University,Lunds universitet,Experimentell kärlforskning,Forskargrupper vid Lunds universitet,Experimental Vascular Research,Lund University Research Groups,Copenhagen University Hospital
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- Engelska 8 s.
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Ingår i: Experimental Eye Research. - : Elsevier BV. - 0014-4835. ; 179, s. 142-149
- Relaterad länk:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Retinal ischemia remains a major cause of blindness in the world with few acute treatments available. Recent emphasis on retinal vasculature and the ophthalmic artery's vascular properties after ischemia has shown an increase in vasoconstrictive functionality, as previously observed in cerebral arteries following stroke. Specifically, endothelin-1 (ET-1) receptor-mediated vasoconstriction regulated by the MEK/ERK1/2 pathway. In this study, the ophthalmic artery of rats was occluded for 2 h with the middle cerebral artery occlusion model. MEK/ERK1/2 inhibitor U0126 was administered at 0, 6, and 24 h following reperfusion and the functional properties of the ophthalmic artery were evaluated at 48 h post reperfusion. Additionally, retinal function was evaluated at day 1, 4, and 7 after reperfusion. Occlusion of the ophthalmic artery led to a significant increase of endothelin-1 mediated vasoconstriction which can be attenuated by U0126 treatment, most evident at higher ET-1 concentrations of 10−7 M (Emax151.0 ± 22.0% of 60 mM K+), vs non-treated ischemic arteries Emax 212.1 ± 14.7% of 60 mM K+). Retinal function also deteriorated following ischemia and was improved with treatment with a-wave amplitudes of 725 ± 36 μV in control, 560 ± 21 μV in non-treated, and 668 ± 73 μV in U0126 treated at 2 log cd*s/m2 luminance in the acute stages (1 days post-ischemia). Full spontaneous retinal recovery was observed at day 7 regardless of treatment. In conclusion, this is the first study to show a beneficial in vivo effect of U0126 on vascular contractility following ischemia in the ophthalmic artery. Coupled with the knowledge obtained from cerebral vasculature, these results point towards a novel therapeutic approach following ischemia-related injuries to the eye.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Oftalmologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Ophthalmology (hsv//eng)
Nyckelord
- Endothelin-1
- mek/erk1/2
- Ophthalmic artery
- Retinal ischemia
- Vascular changes
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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