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Calcitriol and non-...
Calcitriol and non-calcemic vitamin D analogue, 22-oxacalcitriol, attenuate developmental and pathological choroidal vasculature angiogenesis ex vivo and in vivo
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- Merrigan, Stephanie L. (author)
- UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland
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- Park, Bomina (author)
- Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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- Ali, Zaheer (author)
- Linköpings universitet,Avdelningen för kardiovaskulär medicin,Medicinska fakulteten
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- Jensen, Lasse (author)
- Linköpings universitet,Avdelningen för diagnostik och specialistmedicin,Medicinska fakulteten,Region Östergötland, Klinisk farmakologi
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- Corson, Timothy W. (author)
- Eugene and Marilyn Glick Eye Institute, Department of Ophthalmology, Indiana University School of Medicine, Indianapolis, Indiana, USA; Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis,Indiana, USA
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- Kennedy, Breandán N (author)
- UCD School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Ireland
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(creator_code:org_t)
- 2020-02-04
- 2020
- English.
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In: Oncotarget. - : Impact Journals. - 1949-2553. ; 11:5, s. 493-509
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Abstract
Subject headings
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- Aberrant ocular angiogenesis can underpin vision loss in leading causes of blindness, including neovascular age-related macular degeneration and proliferative diabetic retinopathy. Current pharmacological interventions require repeated invasive administrations, may lack efficacy and are associated with poor patient compliance and tachyphylaxis. Vitamin D has de novo anti-angiogenic properties. Here, our aim was to validate the ocular anti-angiogenic activity of biologically active vitamin D, calcitriol, and selected vitamin D analogue, 22-oxacalcitriol. Calcitriol induced a significant reduction in ex vivo mouse choroidal fragment sprouting. Viability studies in a human RPE cell line suggested non-calcemic vitamin D analogues including 22-oxacalcitriol have less off-target anti-proliferative activity compared to calcitriol and other analogues. Thereafter, the anti-angiogenic activity of 22-oxacalcitriol was demonstrated in an ex vivo mouse choroidal fragment sprouting assay. In zebrafish larvae, 22-oxacalcitriol was found to be anti-angiogenic, inducing a dose-dependent reduction in choriocapillaris development. Subcutaneously administered calcitriol failed to attenuate mouse retinal vasculature development. However, calcitriol and 22-oxacalcitriol administered intraperitoneally, significantly attenuated lesion volume in the laser-induced choroidal neovascularisation mouse model. In summary, calcitriol and 22-oxacalcitriol attenuate ex vivo and in vivo choroidal vasculature angiogenesis. Therefore, vitamin D may have potential as an interventional treatment for ophthalmic neovascular indications.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- 22-oxacalcitriol; calcitriol; developmental angiogenesis; ocular angiogenesis; pathological angiogenesis
Publication and Content Type
- ref (subject category)
- art (subject category)
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