Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina
Ischemia/reperfusion (I/R) events are involved in the pathophysiology of numerous ocular diseases. The purpose of this study was to test the hypothesis that betulinic acid protects from I/R injury in the mouse retina. Ocular ischemia was induced in mice by increasing intraocular pressure (IOP) to 11...
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MDPI AG
2021-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/9/2440 |
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| author | Aytan Musayeva Johanna C. Unkrig Mayagozel B. Zhutdieva Caroline Manicam Yue Ruan Panagiotis Laspas Panagiotis Chronopoulos Marie L. Göbel Norbert Pfeiffer Christoph Brochhausen Andreas Daiber Matthias Oelze Huige Li Ning Xia Adrian Gericke |
| author_facet | Aytan Musayeva Johanna C. Unkrig Mayagozel B. Zhutdieva Caroline Manicam Yue Ruan Panagiotis Laspas Panagiotis Chronopoulos Marie L. Göbel Norbert Pfeiffer Christoph Brochhausen Andreas Daiber Matthias Oelze Huige Li Ning Xia Adrian Gericke |
| author_sort | Aytan Musayeva |
| collection | DOAJ |
| description | Ischemia/reperfusion (I/R) events are involved in the pathophysiology of numerous ocular diseases. The purpose of this study was to test the hypothesis that betulinic acid protects from I/R injury in the mouse retina. Ocular ischemia was induced in mice by increasing intraocular pressure (IOP) to 110 mm Hg for 45 min, while the fellow eye served as a control. One group of mice received betulinic acid (50 mg/kg/day p.o. once daily) and the other group received the vehicle solution only. Eight days after the I/R event, the animals were killed and the retinal wholemounts and optic nerve cross-sections were prepared and stained with cresyl blue or toluidine blue, respectively, to count cells in the ganglion cell layer (GCL) of the retina and axons in the optic nerve. Retinal arteriole responses were measured in isolated retinas by video microscopy. The levels of reactive oxygen species (ROS) were assessed in retinal cryosections and redox gene expression was determined in isolated retinas by quantitative PCR. I/R markedly reduced cell number in the GCL and axon number in the optic nerve of the vehicle-treated mice. In contrast, only a negligible reduction in cell and axon number was observed following I/R in the betulinic acid-treated mice. Endothelial function was markedly reduced and ROS levels were increased in retinal arterioles of vehicle-exposed eyes following I/R, whereas betulinic acid partially prevented vascular endothelial dysfunction and ROS formation. Moreover, betulinic acid boosted mRNA expression for the antioxidant enzymes SOD3 and HO-1 following I/R. Our data provide evidence that betulinic acid protects from I/R injury in the mouse retina. Improvement of vascular endothelial function and the reduction in ROS levels appear to contribute to the neuroprotective effect. |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T07:48:19Z |
| publishDate | 2021-09-01 |
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| spelling | doaj.art-60328903705e41018e948969cb3edace2023-11-22T12:26:13ZengMDPI AGCells2073-44092021-09-01109244010.3390/cells10092440Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse RetinaAytan Musayeva0Johanna C. Unkrig1Mayagozel B. Zhutdieva2Caroline Manicam3Yue Ruan4Panagiotis Laspas5Panagiotis Chronopoulos6Marie L. Göbel7Norbert Pfeiffer8Christoph Brochhausen9Andreas Daiber10Matthias Oelze11Huige Li12Ning Xia13Adrian Gericke14Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyInstitute of Pathology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Cardiology 1, Laboratory of Molecular Cardiology, University Medical Center, Johannes Gutenberg University Mainz, Building 605, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Cardiology 1, Laboratory of Molecular Cardiology, University Medical Center, Johannes Gutenberg University Mainz, Building 605, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Pharmacology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Pharmacology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyDepartment of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, GermanyIschemia/reperfusion (I/R) events are involved in the pathophysiology of numerous ocular diseases. The purpose of this study was to test the hypothesis that betulinic acid protects from I/R injury in the mouse retina. Ocular ischemia was induced in mice by increasing intraocular pressure (IOP) to 110 mm Hg for 45 min, while the fellow eye served as a control. One group of mice received betulinic acid (50 mg/kg/day p.o. once daily) and the other group received the vehicle solution only. Eight days after the I/R event, the animals were killed and the retinal wholemounts and optic nerve cross-sections were prepared and stained with cresyl blue or toluidine blue, respectively, to count cells in the ganglion cell layer (GCL) of the retina and axons in the optic nerve. Retinal arteriole responses were measured in isolated retinas by video microscopy. The levels of reactive oxygen species (ROS) were assessed in retinal cryosections and redox gene expression was determined in isolated retinas by quantitative PCR. I/R markedly reduced cell number in the GCL and axon number in the optic nerve of the vehicle-treated mice. In contrast, only a negligible reduction in cell and axon number was observed following I/R in the betulinic acid-treated mice. Endothelial function was markedly reduced and ROS levels were increased in retinal arterioles of vehicle-exposed eyes following I/R, whereas betulinic acid partially prevented vascular endothelial dysfunction and ROS formation. Moreover, betulinic acid boosted mRNA expression for the antioxidant enzymes SOD3 and HO-1 following I/R. Our data provide evidence that betulinic acid protects from I/R injury in the mouse retina. Improvement of vascular endothelial function and the reduction in ROS levels appear to contribute to the neuroprotective effect.https://www.mdpi.com/2073-4409/10/9/2440arteriolesbetulinic acidischemia-reperfusion injuryreactive oxygen speciesretina |
| spellingShingle | Aytan Musayeva Johanna C. Unkrig Mayagozel B. Zhutdieva Caroline Manicam Yue Ruan Panagiotis Laspas Panagiotis Chronopoulos Marie L. Göbel Norbert Pfeiffer Christoph Brochhausen Andreas Daiber Matthias Oelze Huige Li Ning Xia Adrian Gericke Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina Cells arterioles betulinic acid ischemia-reperfusion injury reactive oxygen species retina |
| title | Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina |
| title_full | Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina |
| title_fullStr | Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina |
| title_full_unstemmed | Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina |
| title_short | Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina |
| title_sort | betulinic acid protects from ischemia reperfusion injury in the mouse retina |
| topic | arterioles betulinic acid ischemia-reperfusion injury reactive oxygen species retina |
| url | https://www.mdpi.com/2073-4409/10/9/2440 |
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