<i>In Vitro</i> Study of Antiadipogenic Profile of Latanoprost, Travoprost, Bimatoprost, and Tafluprost in Human Orbital Preadiopocytes

Choi, Hee Young; Lee, Ji Eun; Lee, Jiwoong; Park, Hyun Jun; Jung, Jae Ho

doi:10.1089/jop.2011.0160

Cited by 52 publications

(43 citation statements)

References 29 publications

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“…PGF 2a also inhibited adipogenesis in OFs, as reported by Choi and colleagues (30), although these authors did not investigate cells from GO orbits, whereas our study illustrates that they remain highly responsive to the drug and have not become resistant, for example, by losing PGF 2a receptors.…”

Section: Discussionsupporting

confidence: 78%

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Draman

Grennan-Jones²,

Zhang³

et al. 2013

Thyroid

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Background: In Graves' orbitopathy (GO), increased proliferation, excess adipogenesis, and hyaluronan overproduction produce GO exophthalmos. Enophthalmos occurs in some glaucoma patients treated with Bimatoprost (prostaglandin F 2a , PGF 2a ) eye drops. We hypothesized that enophthalmos is secondary to reductions in orbital tissue proliferation, adipogenesis, and/or increased lipolysis. We aimed to determine which of these is affected by PGF 2a by using the 3T3-L1 murine preadipocyte cell line and primary human orbital fibroblasts (OFs) from GO patients (n = 5) and non-GO (n = 5). Methods: 3T3-L1 cells and orbital OFs were cultured alone or with PGF 2a (all experiments used 10 -8 to 10 -6 M) and counted on days 1/2/3 or 5, respectively; cell cycle analysis (flow cytometry) was applied. Adipogenesis (in the presence/absence of PGF 2a ) was evaluated (day 7 or 15 for 3T3-L1 and primary cells, respectively) morphologically by Oil Red O staining and quantitative polymerase chain reaction measurement of adipogenesis markers (glycerol-3-phosphate dehydrogenase and lipoprotein lipase, respectively). For lipolysis, in vitrodifferentiated 3T3-L1 or mature orbital adipocytes were incubated with norepinephrine and PGF 2a and free glycerol was assayed. Appropriate statistical tests were applied. Results: The population doubling time of 3T3-L1 was 27.3 -1.4 hours-significantly increased by dimethyl sulfoxide 0.02% to 44.6 -4.8 hours ( p = 0.007) and further significantly increased ( p = 0.049 compared with dimethyl sulfoxide) by 10 -8 M PGF 2a to 93.6 -19.0 hours, indicating reduced proliferation, which was caused by prolongation of G2/M. GO OFs proliferated significantly more rapidly than non-GO (population doubling time 5.36 -0.34 or 6.63 -0.35 days, respectively, p = 0.035), but the proliferation of both was significantly reduced (dose dependent from 10 -8 M) by PGF 2a , again with prolongation of G2/M. Adipogenesis in 3T3-L1 cells was minimally affected by PGF 2a when assessed morphologically, but the drug significantly reduced transcripts of the glycerol-3-phosphate dehydrogenase differentiation marker. GO OFs displayed significantly higher adipogenic potential than non-GO, but in both populations, adipogenesis, evaluated by all 3 methods, was significantly reduced (dose dependent from 10 -8 M) by PGF 2a . There was no effect of PGF 2a on basal or norepinephrine-induced lipolysis, in 3T3-L1 or human OFs, either GO or non-GO.Conclusions: The results demonstrate that PGF 2a significantly reduces proliferation and adipogenesis and that human OFs are more sensitive to its effects than 3T3-L1. Consequently, PGF 2a could be effective in the treatment of GO.

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Section: Discussionsupporting

confidence: 78%

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Draman

Grennan-Jones²,

Zhang³

et al. 2013

Thyroid

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“…Filippopoulos et al described upper deep eyelid creases, apparent enophthalmos and attenuation of dermatochalasis (15) . Based mainly on the pharmacological properties of bimatoprost, the hypothesis of these eyelid and orbital changes were resulting from the reduction of preaponeurotic and orbital fat was created (13,16,17) . Although there is a slight difference in the orbital anatomy and physiology among species, the knowledge gained in animal studies can assist in research in humans.…”

Section: Discussionmentioning

confidence: 99%

“…This result suggests that bimatoprost reduces the amount and volume of adipose cells. Choi et al concluded that bimatoprost inhibits both the differentiation of pre-adipocytes and intracellular lipid accumulation (16) . According to Kim, prostaglandin analogues present an inhibitory event especially in the late stage of adipocyte differentiation (17) .…”

Section: Discussionmentioning

confidence: 99%

Changes of orbital connective tissue after bimatoprost injection. Experimental study in rats

Fonseca¹,

Petri²,

Veridiano³

et al. 2016

Revista Brasileira De Oftalmologia

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Rev Bras Oftalmol. 2016; 75 (4): 300-7 RESUMOO bimatoprost é utilizado comumente como a droga de primeira escolha no tratamento do glaucoma primário de ângulo aberto. Hiperemia conjuntival, crescimento dos cílios, enoftalmia, escurecimento cutâneo periocular, sulco palpebral profundo e prurido ocular têm sido relatados em pacientes que receberam bimatoprost em doses únicas diárias durante cerca de 3 meses. O mecanismo exato para estes efeitos adversos permanece desconhecido. Objetivo: Verificar em animais de experimentação, as alterações do tecido conjuntivo orbitário após injeção retrobulbar de bimatoprost 0,03%. Métodos: Foram utilizados trinta e seis ratos machos (Rattus norvegicus albinus) submetidos a diferentes períodos de injeção retrobulbar de bimatoprost à direita. O material exenterado foi submetido à análise histológica, morfométrica (diâmetro, densidade numérica e densidade de volume dos adipócitos) e imunohistoquímica para marcação do VEGF. Os resultados destas análises foram submetidos à análise descritiva com o auxílio do software R. O nível de significância adotado foi 5%. Para as comparações foi proposto o modelo de regressão linear com efeitos mistos. Resultados: Na amostra estudada, as órbitas submetidas a injeções retrobulbares de bimatoprost apresentaram ao redor do nervo óptico tecido conjuntivo mais espesso, com inúmeros capilares e vasos de vários calibres e a redução da quantidade, diâmetro e volume das células adiposas estatisticamente significativo quando comparado à órbita contralateral e ao grupo controle. Conclusão: Neste estudo observaram-se as seguintes alterações potencialmente reversíveis do tecido conjuntivo orbitário nos ratos submetidos à injeção retrobulbar de bimatoprost: 1) redução da quantidade, do diâmetro e do volume das células adiposas orbitárias; 2) neovascularização local; 3) espessamento e remodelamento das fibras de colágeno na cavidade orbitária.Descritores: Antagonistas de prostaglandina/efeitos adversos, Tecido conjuntivo/ efeitos de drogas; Ratos ABSTRACT

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“…These case reports are the first that suggest that this mechanism could also be active in vivo. Choi et al (2012) compared bimatoprost with PGF 2a and three analogs on isolated primary human orbital preadipocytes for antiadipogenic potential. All drug treatments reduced adipocyte differentiation, with bimatoprost producing the most significant reduction (Choi et al, 2012).…”

Section: Adipose Tissuementioning

confidence: 99%

“…Choi et al (2012) compared bimatoprost with PGF 2a and three analogs on isolated primary human orbital preadipocytes for antiadipogenic potential. All drug treatments reduced adipocyte differentiation, with bimatoprost producing the most significant reduction (Choi et al, 2012). Although this study highlights that adipocytes from the target tissue are affected similar to other adipocytes in vitro, a lack of dose-ranging studies leaves the relative effectiveness of any one drug in question.…”

Section: Adipose Tissuementioning

confidence: 99%

Recent Progress in Prostaglandin F₂_αEthanolamide (Prostamide F₂_α) Research and Therapeutics

2013

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In Vitro Study of Antiadipogenic Profile of Latanoprost, Travoprost, Bimatoprost, and Tafluprost in Human Orbital Preadiopocytes

Cited by 52 publications

References 29 publications

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Changes of orbital connective tissue after bimatoprost injection. Experimental study in rats

Recent Progress in Prostaglandin F₂_αEthanolamide (Prostamide F₂_α) Research and Therapeutics

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In Vitro Study of Antiadipogenic Profile of Latanoprost, Travoprost, Bimatoprost, and Tafluprost in Human Orbital Preadiopocytes

Cited by 52 publications

References 29 publications

Effects of Prostaglandin F2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Effects of Prostaglandin F2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Changes of orbital connective tissue after bimatoprost injection. Experimental study in rats

Recent Progress in Prostaglandin F2αEthanolamide (Prostamide F2α) Research and Therapeutics

Contact Info

Product

Resources

About

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Effects of Prostaglandin F_2αon Adipocyte Biology Relevant to Graves' Orbitopathy

Recent Progress in Prostaglandin F₂_αEthanolamide (Prostamide F₂_α) Research and Therapeutics