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UPARANT 是一种有效的抗血管生成药物，可用于治疗虹膜新生血管的小鼠模型。

UPARANT is an effective antiangiogenic agent in a mouse model of rubeosis iridis.

机构信息

Department of Clinical Neuroscience, Division of Eye and Vision, St Erik Eye Hospital, Karolinska Institutet, Polhemsgatan 50, 112 82, Stockholm, Sweden.

Department of Biology, University of Pisa, Pisa, Italy.

出版信息

J Mol Med (Berl). 2019 Sep;97(9):1273-1283. doi: 10.1007/s00109-019-01794-w. Epub 2019 Jun 26.

DOI:10.1007/s00109-019-01794-w
PMID:31243519
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6713680/
Abstract

Puncture-induced iris neovascularization (rubeosis iridis; RI) in mice is associated with upregulation of extracellular matrix (ECM) degradation and inflammatory factors. The anti-angiogenic and anti-inflammatory efficacy of UPARANT in reducing RI was determined by noninvasive, in vivo iris vascular densitometry, and confirmed in vitro by quantitative vascular-specific immunostaining. Intravitreal administration of UPARANT successfully and rapidly reduced RI to non-induced control levels. Molecular analysis revealed that UPARANT inhibits formyl peptide receptors through a predominantly anti-inflammatory response, accompanied with a significant reduction in ECM degradation and inflammation markers. Similar results were observed with UPARANT administered systemically by subcutaneous injection. These data suggest that the tetrapeptide UPARANT is an effective anti-angiogenic agent for the treatment of RI, both by local and systemic administrations. The effectiveness of UPARANT in reducing RI in a model independent of the canonical vascular endothelial growth factor (VEGF) proposes an alternative for patients that do not respond to anti-VEGF treatments, which could improve treatment in proliferative ocular diseases. KEY MESSAGES: UPARANT is effective in the treatment of rubeosis iridis, both by local and systemic administrations. UPARANT can reduce VEGF-independent neovascularization.

摘要

在小鼠中，穿刺诱导的虹膜新生血管形成（虹膜新生血管；RI）与细胞外基质（ECM）降解和炎症因子的上调有关。通过非侵入性、体内虹膜血管密度测定法，以及体外定量血管特异性免疫染色法，确定 UPARANT 在减少 RI 方面的抗血管生成和抗炎功效。玻璃体内给予 UPARANT 可成功且快速地将 RI 降低至非诱导对照水平。分子分析表明，UPARANT 通过主要的抗炎反应抑制甲酰肽受体，同时 ECM 降解和炎症标志物显著减少。通过皮下注射全身给予 UPARANT 也观察到类似的结果。这些数据表明，四肽 UPARANT 是治疗 RI 的有效抗血管生成剂，无论是局部还是全身给药。UPARANT 在独立于经典血管内皮生长因子（VEGF）的模型中降低 RI 的有效性提出了一种替代方案，适用于对抗 VEGF 治疗无反应的患者，这可以改善增殖性眼病的治疗效果。关键信息：UPARANT 对虹膜新生血管的治疗有效，无论是局部还是全身给药。UPARANT 可减少 VEGF 非依赖性新生血管形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/0b53f813a561/109_2019_1794_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/42c2ef17d808/109_2019_1794_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/8401b96dcc35/109_2019_1794_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/8662f704e86a/109_2019_1794_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/0a04a451f974/109_2019_1794_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/21e5fcc511d9/109_2019_1794_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/0b53f813a561/109_2019_1794_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/42c2ef17d808/109_2019_1794_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/8401b96dcc35/109_2019_1794_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/8662f704e86a/109_2019_1794_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/0a04a451f974/109_2019_1794_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/21e5fcc511d9/109_2019_1794_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0579/6713680/0b53f813a561/109_2019_1794_Fig6_HTML.jpg

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