التفاصيل البيبلوغرافية
| العنوان: |
3K3A-Activated Protein C Inhibits Choroidal Neovascularization Growth and Leakage and Reduces NLRP3 Inflammasome, IL-1β, and Inflammatory Cell Accumulation in the Retina |
| المؤلفون: |
Yehonatan Weinberger, Ivan Budnik, Yael Nisgav, Dahlia Palevski, Gil Ben-David, José A. Fernández, Shany Nivinsky Margalit, Sarina Levy-Mendelovich, Gili Kenet, Dov Weinberger, John H. Griffin, Tami Livnat |
| المصدر: |
International Journal of Molecular Sciences; Volume 24; Issue 13; Pages: 10642 |
| بيانات النشر: |
Multidisciplinary Digital Publishing Institute |
| سنة النشر: |
2023 |
| المجموعة: |
MDPI Open Access Publishing |
| مصطلحات موضوعية: |
activated protein C, choroidal neovascularization, inflammation NLRP3, microglia |
| جغرافية الموضوع: |
agris |
| الوصف: |
3K3A-Activated Protein C (APC) is a recombinant variant of the physiological anticoagulant APC with cytoprotective properties and reduced bleeding risks. We studied the potential use of 3K3A-APC as a multi-target therapeutic option for choroidal neovascularization (CNV), a common cause of vision loss in age-related macular degeneration. CNV was induced by laser photocoagulation in a murine model, and 3K3A-APC was intravitreally injected. The impact of 3K3A-APC treatment on myeloid and microglia cell activation and recruitment and on NLRP3 inflammasome, IL-1β, and VEGF levels was assessed using cryosection, retinal flat-mount immunohistochemistry and vascular imaging. Additionally, we evaluated the use of fluorescein angiography as a surrogate marker for in vivo evaluation of the efficacy of 3K3A-APC treatment against leaking CNV lesions. Our results demonstrated that 3K3A-APC treatment significantly reduced the accumulation and activation of myeloid cells and microglia in the CNV area and decreased the NLRP3 and IL-1β levels at the CNV site and the surrounding retina. Furthermore, 3K3A-APC treatment resulted in leakage regression and CNV growth suppression. These findings indicate that the anti-inflammatory activities of 3K3A-APC contribute to CNV inhibition. Our study suggests the potential use of 3K3A-APC as a novel multi-target treatment for CNV. |
| نوع الوثيقة: |
text |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| Relation: |
Molecular Pathology, Diagnostics, and Therapeutics; https://dx.doi.org/10.3390/ijms241310642 |
| DOI: |
10.3390/ijms241310642 |
| الاتاحة: |
https://doi.org/10.3390/ijms241310642 |
| Rights: |
https://creativecommons.org/licenses/by/4.0/ |
| رقم الانضمام: |
edsbas.4CBD3397 |
| قاعدة البيانات: |
BASE |