Dr. Nasser Al-Rashid Orbital Vision Research Center, Bascom Palmer Eye Institute, Department of Ophthalmology, McKnight Vision Research Center, University of Miami School of Medicine, Miami, Florida, United States.
Department of Biomedical Engineering, University of Miami Miller School of Medicine, Miami, Florida, United States.
Invest Ophthalmol Vis Sci. 2018 Dec 3;59(15):5912-5923. doi: 10.1167/iovs.18-25134.
We characterize the effect of bimatoprost on orbital adipose tissue in thyroid-associated orbitopathy (TAO) with clinicopathologic correlation.
Orbital adipose-derived stem cells (OASCs) from types 1 and 2 TAO and control patients with and without exposure to 1 μm bimatoprost were examined via immunohistochemistry, RT-PCR, and Western blot for cell viability, migration capacity, lipid content, adipocyte morphology, mitochondrial content, and levels of adipogenic markers. A retrospective chart review was performed for clinicopathologic correlation. In mice, optical coherence tomography and pattern electroretinography were performed at baseline and at 1 month following a retrobulbar injection of bimatoprost, followed by orbital exenteration for histopathologic examination.
Types 1 and 2 TAO-derived cells had a significantly higher migration capacity and lipid content than those of healthy controls. With the addition of bimatoprost, types 1 and 2 TAO and control adipocytes exhibited a significant decrease in lipid content with morphologic transformation into smaller and multilocular lipid droplets, and an increase in mitochondrial load and UCP-1 expression consistent with an increase in brown adipose tissue turnover. Retrobulbar injection of bimatoprost in mice did not alter the gross morphology, retinal thickness, or ganglion cell function in vivo.
Bimatoprost inhibits adipogenesis in OASCs and upregulates pathways involved in the browning of adipocytes. Furthermore, retrobulbar injection of bimatoprost is tolerated without immediate adverse effects in mice. Our results suggest a potential future application of prostaglandin analogues in the treatment of TAO.
我们通过临床病理相关性研究，来描述贝美前列素对甲状腺相关眼病（TAO）眼眶脂肪组织的影响。
通过免疫组织化学、RT-PCR 和 Western blot 检测，研究了 1 型和 2 型 TAO 患者以及未接触过 1 μm 贝美前列素的对照组患者眼眶脂肪来源干细胞（OASCs）的细胞活力、迁移能力、脂质含量、脂肪细胞形态、线粒体含量和脂肪生成标志物水平。对临床病理相关性进行了回顾性图表审查。在小鼠中，在眼眶内注射贝美前列素前和 1 个月后进行光学相干断层扫描和图形视网膜电图检查，然后进行眼眶切除术进行组织病理学检查。
1 型和 2 型 TAO 来源的细胞比健康对照组具有更高的迁移能力和脂质含量。在加入贝美前列素后，1 型和 2 型 TAO 和对照组脂肪细胞的脂质含量明显减少，形态转化为更小和多腔脂质滴，并增加线粒体负荷和 UCP-1 表达，这与棕色脂肪组织周转的增加一致。在小鼠中眼眶内注射贝美前列素不会改变体内的大体形态、视网膜厚度或节细胞功能。
贝美前列素抑制 OASCs 的脂肪生成，并上调参与脂肪细胞棕色化的途径。此外，在小鼠中眼眶内注射贝美前列素耐受性良好，无即刻不良反应。我们的研究结果表明，前列腺素类似物在 TAO 的治疗中具有潜在的应用前景。
Zotero 插件
