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Article

Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina

1
Department of Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
2
Laboratory of Corneal Immunology, Transplantation and Regeneration, Schepens Eye Research Institute, Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA
3
Institute of Pathology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
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Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
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Department of Cardiology 1, Laboratory of Molecular Cardiology, University Medical Center, Johannes Gutenberg University Mainz, Building 605, Langenbeckstrasse 1, 55131 Mainz, Germany
6
Department of Pharmacology, University Medical Center, Johannes Gutenberg University Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Maurice Ptito and Joseph Bouskila
Cells 2021, 10(9), 2440; https://doi.org/10.3390/cells10092440
Received: 30 August 2021 / Revised: 10 September 2021 / Accepted: 14 September 2021 / Published: 16 September 2021
(This article belongs to the Special Issue The Retina in Health and Disease)
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. View Full-Text
Keywords: arterioles; betulinic acid; ischemia-reperfusion injury; reactive oxygen species; retina arterioles; betulinic acid; ischemia-reperfusion injury; reactive oxygen species; retina
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MDPI and ACS Style

Musayeva, A.; Unkrig, J.C.; Zhutdieva, M.B.; Manicam, C.; Ruan, Y.; Laspas, P.; Chronopoulos, P.; Göbel, M.L.; Pfeiffer, N.; Brochhausen, C.; Daiber, A.; Oelze, M.; Li, H.; Xia, N.; Gericke, A. Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina. Cells 2021, 10, 2440. https://doi.org/10.3390/cells10092440

AMA Style

Musayeva A, Unkrig JC, Zhutdieva MB, Manicam C, Ruan Y, Laspas P, Chronopoulos P, Göbel ML, Pfeiffer N, Brochhausen C, Daiber A, Oelze M, Li H, Xia N, Gericke A. Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina. Cells. 2021; 10(9):2440. https://doi.org/10.3390/cells10092440

Chicago/Turabian Style

Musayeva, Aytan, 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, and Adrian Gericke. 2021. "Betulinic Acid Protects from Ischemia-Reperfusion Injury in the Mouse Retina" Cells 10, no. 9: 2440. https://doi.org/10.3390/cells10092440

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