Department of Ophthalmology, Pusan National University Hospital, Busan, Korea.
J Ocul Pharmacol Ther. 2012 Apr;28(2):146-52. doi: 10.1089/jop.2011.0160. Epub 2011 Nov 22.
To investigate the effect of prostaglandin F2α (PGF2α), latanoprost, travoprost, bimatoprost, and tafluprost on human orbital preadipocyte differentiation and intracellular lipid storage, and to reveal the potential mechanisms by which topical prostaglandin analogs induce orbital fat volume reduction and cause deep superior sulcus syndrome.
Human orbital adipose precursors were treated in vitro for 24 h (day 1) with PGF2α, latanoprost, travoprost, bimatoprost, and tafluprost in their commercial formulations (1:100 dilution). Expressions of adipogenic transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ), and CCAAT-enhancer-binding protein α (C/EBPα) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) at day 7. At 14 days, cells were stained with oil red O, intracellular lipid accumulation was evaluated by lipid absorbance, and adipocyte expression marker [Lipoprotein lipase (LPL)] was determined by real-time RT-PCR.
Our results showed that PGF2α and topical prostaglandin analogs down-regulated the expression of PPARγ and C/EBPα, and inhibited accumulation of intra-cytoplasmic lipid droplets and expression of LPL compared with the untreated control. Comparison between the 4 drugs showed that latanoprost had the weakest antiadipogenic effect, and bimatoprost induced the most significant reduction of adipogenesis.
Latanoprost, travoprost, bimatoprost, and tafluprost inhibited human preadipocyte differentiation and intracellular lipid accumulation. Morphologic and metabolic changes in orbital adipocytes caused by PGF2α analogs are a possible pathophysiologic explanation of superior eyelid deepening in patients with glaucoma.
研究前列腺素 F2α（PGF2α）、拉坦前列素、曲伏前列素、贝美前列素和他氟前列素对人眼眶前脂肪细胞分化和细胞内脂质储存的影响，揭示局部前列腺素类似物引起眼眶脂肪体积减少并导致深上睑沟综合征的潜在机制。
体外培养人眼眶脂肪前体细胞 24 小时（第 1 天），用前列腺素 F2α、拉坦前列素、曲伏前列素、贝美前列素和他氟前列素的商业制剂（1:100 稀释）处理。第 7 天通过实时逆转录-聚合酶链反应（RT-PCR）测定脂肪生成转录因子、过氧化物酶体增殖物激活受体-γ（PPARγ）和 CCAAT 增强子结合蛋白-α（C/EBPα）的表达。第 14 天，用油红 O 染色，用脂质吸光度评估细胞内脂质积累，用实时 RT-PCR 测定脂肪细胞表达标志物（脂蛋白脂肪酶[LPL]）。
结果表明，PGF2α 和局部前列腺素类似物下调 PPARγ 和 C/EBPα 的表达，并抑制细胞内脂质滴的积累和 LPL 的表达，与未处理的对照组相比。4 种药物的比较表明，拉坦前列素的抗脂肪生成作用最弱，贝美前列素诱导的脂肪生成减少最显著。
拉坦前列素、曲伏前列素、贝美前列素和他氟前列素抑制人前脂肪细胞分化和细胞内脂质积累。PGF2α 类似物引起眼眶脂肪细胞形态和代谢变化可能是青光眼患者上睑加深的病理生理解释。
