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Zhuxi Wang, Reiko Yamagishi, Takashi Fujishiro, Makoto Aihara; Effect Of Prostaglandin Analogues On Inhibition Of Adipocytes Differentiation And Adipogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3102.
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Prostaglandin analogues (PGs) are widely used for anti-glaucoma therapy. Recently, deepening of upper eyelid sulcus (DUES) are reported as cosmetic side effects in bimatoprost and travoprost, but not in latanoprost. However, the mechanism of DUES is unclear. We hypothesized orbital fat reduction is one of the causes of DUES, and planned to study the effect of PGs on adipogenesis in vitro.
3T3-L1 preadipocytes were cultured and differentiated into adipocytes (day 0). At day 2, unoprostone (UNO), latanoprost acid (LAT-A), travoprost acid (TRA-A), tafluprost acid (TAF-A), bimatoprost (BIM), bimatoprost acid (BIM-A), and prostaglandin F2a (PGF2a) were added at the concentration of 100nM. At day 10, intracellular oil stained with Oil Red O were photographed by a microscopy to measure the area of oil. In one assay using all drugs, 50 areas were counted and 5 dependent experiments were repeated in a masked manner. The relative area of oil in the treated culture was calculated in comparison with that in the control culture with DMSO vehicle solution and analyzed by Dunnet test.
The relative oil area of LAT-A, TRA-A, TAF-A, BIM, BIM-A, UNO and PGF2a were 35.8±18.7, 25.8±11.7, 41.2±22.3, 112.7±61.0, 17.9±9.0, 100.9±43.2, and 45.2±38.0%, respectively. All acid form of prost-type PGs, LAT-A, TRA-A, TAF-A, BIM-A, and PGF2a inhibited adipogenesis. TRA-A and BIM-A significantly inhibited adipogenesis (p<0.05), but BIM and UNO did not. Prost-type PGs with high FP receptor affinity tended to show strong inhibitory effect compared to prostamide-type BIM and prostone-type UNO.
Although DUES were not clarified in all PGs, all acid forms of prost-type FP agonists were more potent than BIM and UNO in interfering adipogenesis in vitro. This result suggests that all prost-type PG analogues may have a potential to induce DUES, probably due to orbital fat reduction.
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