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Invest Ophthalmol Vis Sci. 2020 Jun 3;61(6):13. doi: 10.1167/iovs.61.6.13.
To elucidate the molecular etiology of deepening of the upper eyelid sulcus (DUES) induced by prostaglandin (PG) analogs, a three-dimensional (3D) tissue culture system was employed using human orbital fibroblasts (HOFs).
During adipogenesis, changes in HOF 3D organoid sizes, as well as their lipids stained by BODIPY and expression of the extracellular matrix (ECM) by immunolabeling and/or quantitative PCR, were studied in the presence or absence of either 100-nM bimatoprost acid or 100-nM prostaglandin F2α.
The size of the 3D organoids increased remarkably during adipogenesis, but such increases were significantly inhibited by the presence of PG analogs. Staining intensities by BODIPY and mRNA expression of peroxisome proliferator-activated receptor gamma were significantly increased upon adipogenesis but were not influenced by the presence of PG analogs. Unique changes in ECM expression observed with or without adipogenic differentiation were significantly modified by the presence of PG analogs.
Our present study indicates that PG analogs have the potential to modulate the ECM network within HOF 3D organoids. Thus, a 3D tissue culture system may be a suitable strategy for understanding the disease etiology of DUES.
为阐明前列腺素（PG）类似物引起的上睑沟加深（DUES）的分子病因学，我们采用了三维（3D）人眼眶成纤维细胞（HOF）组织培养系统。
在脂肪生成过程中，研究了存在或不存在 100nM 比马前列素酸或 100nM 前列腺素 F2α时，HOF 3D 类器官大小的变化，以及它们被 BODIPY 染色的脂质和细胞外基质（ECM）的免疫标记和/或定量 PCR 表达。
3D 类器官在脂肪生成过程中显著增大，但 PG 类似物的存在显著抑制了这种增大。脂肪生成时，BODIPY 染色强度和过氧化物酶体增殖物激活受体γ的 mRNA 表达显著增加，但不受 PG 类似物的影响。有或无脂肪生成分化时观察到的 ECM 表达的独特变化，受 PG 类似物的存在显著改变。
本研究表明，PG 类似物具有调节 HOF 3D 类器官内 ECM 网络的潜力。因此，3D 组织培养系统可能是理解 DUES 疾病病因的合适策略。
