| Autor: |
Santiago Delgado-Tirado, MD, Lucia Gonzalez-Buendia, MD, Miranda An, BA, Dhanesh Amarnani, MS, Daniela Isaacs-Bernal, BSc, Hannah Whitmore, PhD, Said Arevalo-Alquichire, PhD, David Leyton-Cifuentes, BME, Jose M. Ruiz-Moreno, MD, PhD, Joseph F. Arboleda-Velasquez, MD, PhD, Leo A. Kim, MD, PhD |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Ophthalmology Science, Vol 2, Iss 3, Pp 100163- (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2666-9145 |
| DOI: |
10.1016/j.xops.2022.100163 |
| Popis: |
Purpose: To test the efficacy of runt-related transcription factor 1 (RUNX1) inhibition with topical nanoemulsion containing Ro5-3335 (eNano-Ro5) in experimental ocular neovascularization. Design: Preclinical experimental study. Participants: In vitro primary culture human retinal endothelial cell (HREC) culture. C57BL/6J 6- to 10-week-old male and female mice. Methods: We evaluated the effect of eNano-Ro5 in cell proliferation, cell toxicity, and migration of HRECs. We used an alkali burn model of corneal neovascularization and a laser-induced model of choroidal neovascularization to test in vivo efficacy of eNano-Ro5 in pathologic angiogenesis in mice. We used mass spectrometry to measure penetration of Ro5-3335 released from the nanoemulsion in ocular tissues. Main Outcome Measures: Neovascular area. Results: RUNX1 inhibition reduced cell proliferation and migration in vitro. Mass spectrometry analysis revealed detectable levels of the active RUNX1 small-molecule inhibitor Ro5-3335 in the anterior and posterior segment of the mice eyes. Topical treatment with eNano-Ro5 significantly reduced corneal neovascularization and improved corneal wound healing after alkali burn. Choroidal neovascularization lesion size and leakage were significantly reduced after treatment with topical eNano-Ro5. Conclusions: Topical treatment with eNano-Ro5 is an effective and viable platform to deliver a small-molecule RUNX1 inhibitor. This route of administration offers advantages that could improve the management and outcomes of these sight-threatening conditions. Topical noninvasive delivery of RUNX1 inhibitor could be beneficial for many patients with pathologic ocular neovascularization. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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