Effect of sorafenib in a murine high risk penetrating keratoplasty model
AIM: To evaluate the effect of sorafenib in murine high risk keratoplasty model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone, dimethyl sulfoxide (DMSO), and phosphate buffered saline (PBS) groups following subco...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Press of International Journal of Ophthalmology (IJO PRESS)
2017-06-01
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| Series: | International Journal of Ophthalmology |
| Subjects: | |
| Online Access: | http://www.ijo.cn/en_publish/2017/6/20170602.pdf |
| _version_ | 1811279188249804800 |
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| author | Yang Kyung Cho Eun Young Shin Hironori Uehara Balamurali K Ambati |
| author_facet | Yang Kyung Cho Eun Young Shin Hironori Uehara Balamurali K Ambati |
| author_sort | Yang Kyung Cho |
| collection | DOAJ |
| description | AIM: To evaluate the effect of sorafenib in murine high risk keratoplasty model.
METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone, dimethyl sulfoxide (DMSO), and phosphate buffered saline (PBS) groups following subconjunctival injection in mice that underwent high risk penetrating keratoplasty (HRPK). Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3.
RESULTS: The two-month graft survival rate for HRPK was 42.86% in sorafenib group, 37.50% in dexamethasone group, 0 in DMSO group, and 0 in PBS group. Sorafenib significantly increased graft survival compared to the DMSO and PBS group (P<0.05). The sorafenib didn’t show significant effect in decreasing neovascularization compared with dexamethsone, DMSO, and PBS group. The sorafenib showed less total lymphangiogenesis than the dexamethasone, DMSO, and PBS group (P=0.011, P<0.001, P<0.001, respectively). The sorafenib group showed reduced expression of VEGF-C, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, VEGFR-2 and VEGFR-3 compared with DMSO group and PBS group (all P<0.05). The sorafenib group didn’t show difference in the expression of VEGF-A compared with DMSO, neither with PBS. The sorafenib group showed reduced expression of VEGFR-3 compared with dexamethasone (P=0.051).
CONCLUSION: The subconjunctivally administered sorafenib shows significant anti-lymphangiogenic effect, resulting in increased transplant survival in a murine high risk keratoplasty model. We suggest that a close linkage between decreased VEGF-C/VEGFR-2 and -3 signaling and increased corneal graft survival by sorafenib seems to exist. |
| first_indexed | 2024-04-13T00:50:10Z |
| format | Article |
| id | doaj.art-d7a5bb582aae4ed2982224c050ea4692 |
| institution | Directory Open Access Journal |
| issn | 2222-3959 2227-4898 |
| language | English |
| last_indexed | 2024-04-13T00:50:10Z |
| publishDate | 2017-06-01 |
| publisher | Press of International Journal of Ophthalmology (IJO PRESS) |
| record_format | Article |
| series | International Journal of Ophthalmology |
| spelling | doaj.art-d7a5bb582aae4ed2982224c050ea46922022-12-22T03:09:54ZengPress of International Journal of Ophthalmology (IJO PRESS)International Journal of Ophthalmology2222-39592227-48982017-06-0110683483910.18240/ijo.2017.06.02Effect of sorafenib in a murine high risk penetrating keratoplasty modelYang Kyung Cho0Eun Young Shin1Hironori Uehara2Balamurali K Ambati3Department of Ophthalmology, St.Vincent’s Hospital, College of Medicine, the Catholic University of Korea, Suwon, Gyeonggi-Do 16247, KoreaResearch Institute of Medical Science, St.Vincent's Hospital, College of Medicine, the Catholic University of Korea, Suwon, Gyeonggi-Do 16247, KoreaDepartment of Ophthalmology, University of Utah, School of Medicine, Salt Lake City, Utah 84132, USADepartment of Ophthalmology, University of Utah, School of Medicine, Salt Lake City, Utah 84132, USAAIM: To evaluate the effect of sorafenib in murine high risk keratoplasty model. METHODS: Graft survival, corneal neovascularization, and corneal lymphangiogenesis were compared among the sorafenib, dexamethasone, dimethyl sulfoxide (DMSO), and phosphate buffered saline (PBS) groups following subconjunctival injection in mice that underwent high risk penetrating keratoplasty (HRPK). Real-time polymerase chain reaction was performed to quantify the expression of inflammatory cytokines and vascular endothelial growth factor (VEGF)-A, VEGF-C, vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3. RESULTS: The two-month graft survival rate for HRPK was 42.86% in sorafenib group, 37.50% in dexamethasone group, 0 in DMSO group, and 0 in PBS group. Sorafenib significantly increased graft survival compared to the DMSO and PBS group (P<0.05). The sorafenib didn’t show significant effect in decreasing neovascularization compared with dexamethsone, DMSO, and PBS group. The sorafenib showed less total lymphangiogenesis than the dexamethasone, DMSO, and PBS group (P=0.011, P<0.001, P<0.001, respectively). The sorafenib group showed reduced expression of VEGF-C, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, VEGFR-2 and VEGFR-3 compared with DMSO group and PBS group (all P<0.05). The sorafenib group didn’t show difference in the expression of VEGF-A compared with DMSO, neither with PBS. The sorafenib group showed reduced expression of VEGFR-3 compared with dexamethasone (P=0.051). CONCLUSION: The subconjunctivally administered sorafenib shows significant anti-lymphangiogenic effect, resulting in increased transplant survival in a murine high risk keratoplasty model. We suggest that a close linkage between decreased VEGF-C/VEGFR-2 and -3 signaling and increased corneal graft survival by sorafenib seems to exist.http://www.ijo.cn/en_publish/2017/6/20170602.pdf839sorafenibneovascularizationgraft survivallymphangiogenesisdexamethasone |
| spellingShingle | Yang Kyung Cho Eun Young Shin Hironori Uehara Balamurali K Ambati Effect of sorafenib in a murine high risk penetrating keratoplasty model International Journal of Ophthalmology 839 sorafenib neovascularization graft survival lymphangiogenesis dexamethasone |
| title | Effect of sorafenib in a murine high risk penetrating keratoplasty model |
| title_full | Effect of sorafenib in a murine high risk penetrating keratoplasty model |
| title_fullStr | Effect of sorafenib in a murine high risk penetrating keratoplasty model |
| title_full_unstemmed | Effect of sorafenib in a murine high risk penetrating keratoplasty model |
| title_short | Effect of sorafenib in a murine high risk penetrating keratoplasty model |
| title_sort | effect of sorafenib in a murine high risk penetrating keratoplasty model |
| topic | 839 sorafenib neovascularization graft survival lymphangiogenesis dexamethasone |
| url | http://www.ijo.cn/en_publish/2017/6/20170602.pdf |
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