AAV2 delivery of Flt23k intraceptors inhibits murine choroidal neovascularization
Long-term inhibition of extracellular vascular endothelial growth factor (VEGF) in the treatment of age-related macular degeneration (AMD) may induce retinal neuronal toxicity and risk other side effects. We developed a novel strategy which inhibits retinal pigment epithelium (RPE)-derived VEGF, sparing other highly sensitive retinal tissues. Flt23k, an intraceptor inhibitor of VEGF, was able to inhibit VEGF in vitro. Adeno-associated virus type 2 (AAV2)-mediated expression of Flt23k was maintained for up to 6 months postsubretinal injection in mice. Flt23k was able to effectively inhibit laser-induced murine choroidal neovascularization (CNV). VEGF levels in the RPE/choroid complex decreased significantly in AAV2.Flt23k treated eyes. Neither retinal structure detected by Heidelberg Spectralis nor function measured by electroretinography (ERG) was adversely affected by treatment with AAV2.Flt23k. Hence AAV2.Flt23k can effectively maintain long-term expression and inhibit laser-induced CNV in mice through downregulation of VEGF while maintaining a sound retinal safety profile. These findings suggest a promising novel approach for the treatment of CNV.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Molecular therapy : the journal of the American Society of Gene Therapy - 23(2015), 2 vom: 21. Feb., Seite 226-34 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Xiaohui [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.02.2016 Date Revised 10.03.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/mt.2014.199 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM242701310 |
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| 245 | 1 | 0 | |a AAV2 delivery of Flt23k intraceptors inhibits murine choroidal neovascularization |
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| 500 | |a Date Revised 10.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Long-term inhibition of extracellular vascular endothelial growth factor (VEGF) in the treatment of age-related macular degeneration (AMD) may induce retinal neuronal toxicity and risk other side effects. We developed a novel strategy which inhibits retinal pigment epithelium (RPE)-derived VEGF, sparing other highly sensitive retinal tissues. Flt23k, an intraceptor inhibitor of VEGF, was able to inhibit VEGF in vitro. Adeno-associated virus type 2 (AAV2)-mediated expression of Flt23k was maintained for up to 6 months postsubretinal injection in mice. Flt23k was able to effectively inhibit laser-induced murine choroidal neovascularization (CNV). VEGF levels in the RPE/choroid complex decreased significantly in AAV2.Flt23k treated eyes. Neither retinal structure detected by Heidelberg Spectralis nor function measured by electroretinography (ERG) was adversely affected by treatment with AAV2.Flt23k. Hence AAV2.Flt23k can effectively maintain long-term expression and inhibit laser-induced CNV in mice through downregulation of VEGF while maintaining a sound retinal safety profile. These findings suggest a promising novel approach for the treatment of CNV | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Das, Subrata K |e verfasserin |4 aut | |
| 700 | 1 | |a Passi, Samuel F |e verfasserin |4 aut | |
| 700 | 1 | |a Uehara, Hironori |e verfasserin |4 aut | |
| 700 | 1 | |a Bohner, Austin |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Marcus |e verfasserin |4 aut | |
| 700 | 1 | |a Tiem, Michelle |e verfasserin |4 aut | |
| 700 | 1 | |a Archer, Bonnie |e verfasserin |4 aut | |
| 700 | 1 | |a Ambati, Balamurali K |e verfasserin |4 aut | |
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