PMID- 34003984
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20210628
IS  - 2164-2591 (Electronic)
IS  - 2164-2591 (Linking)
VI  - 10
IP  - 4
DP  - 2021 Apr 1
TI  - Omidenepag, a Selective, Prostanoid EP2 Agonist, Does Not Suppress Adipogenesis 
      in 3D Organoids of Human Orbital Fibroblasts.
PG  - 6
LID - 10.1167/tvst.10.4.6 [doi]
LID - 6
AB  - PURPOSE: The purpose of this study was to present the effects of the prostanoid 
      EP2 agonist, omidenepag (OMD) on human orbital fibroblasts (HOFs) using a 
      three-dimension (3D) cell culture. METHODS: During adipogenesis of 3D HOFs 
      organoids, changes in size, lipids staining, mRNA expression of adipogenesis 
      related genes, PPARgamma, AP2, and ADIPOQ, and extracellular matrix, collagen 1 (COL 
      1), COL 4, COL 6, and fibronectin (FN), and stiffness by a micro-squeezer were 
      examined in the presence and absence of either 100 nM bimatoprost acid (BIM-A) or 
      10, 100, or 10,000 nM OMD. RESULTS: The size of the 3D organoids increased 
      dramatically during adipogenesis, and these were further enhanced in the presence 
      of OMD in contrast to the BIM-A induced suppression effect. The intensity of 
      lipid staining and the mRNA expression of PPARgamma were significantly increased upon 
      adipogenesis, and both or latter was markedly inhibited in the presence of OMD or 
      BIM-A, respectively. AP2 expression was also upregulated by adipogenesis, and was 
      further enhanced by BIM-A. The adipogenesis-induced downregulation of COL 1 and 
      FN, or the upregulation of the expression of COL 4 and COL 6 were all suppressed 
      in the presence of BIM-A. In contrast, OMD caused similar effects on COL 4, COL 
      6, or FN expression, but caused a significant increase in COL 1 expression. 
      Stiffness was significantly increased upon adipogenesis, and was further 
      increased or substantially decreased by BIM-A or OMD, respectively. CONCLUSIONS: 
      The present study indicates that the FP2 agonist, OMD, had different effects on 
      3D HOFs organoids, as compared to BIM-A. TRANSLATIONAL RELEVANCE: The current 
      study suggests that OMD may not induce deepening of upper eyelid sulcus (DUES).
FAU - Hikage, Fumihito
AU  - Hikage F
AD  - Department of Ophthalmology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Ida, Yosuke
AU  - Ida Y
AD  - Department of Ophthalmology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Ouchi, Yuika
AU  - Ouchi Y
AD  - Department of Ophthalmology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Watanabe, Megumi
AU  - Watanabe M
AD  - Department of Ophthalmology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
FAU - Ohguro, Hiroshi
AU  - Ohguro H
AD  - Department of Ophthalmology, Sapporo Medical University School of Medicine, 
      Sapporo, Japan.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Transl Vis Sci Technol
JT  - Translational vision science & technology
JID - 101595919
RN  - 0 (Prostaglandins)
RN  - QXS94885MZ (Bimatoprost)
SB  - IM
MH  - *Adipogenesis/genetics
MH  - Bimatoprost/pharmacology
MH  - Fibroblasts
MH  - Humans
MH  - *Organoids
MH  - Prostaglandins
PMC - PMC8039573
COIS- Disclosure: F. Hikage, None; Y. Ida, None; Y. Ouchi, None; M. Watanabe, None; K. 
      Ohguro, None
EDAT- 2021/05/19 06:00
MHDA- 2021/06/29 06:00
PMCR- 2021/04/12
CRDT- 2021/05/18 17:23
PHST- 2021/05/18 17:23 [entrez]
PHST- 2021/05/19 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2021/04/12 00:00 [pmc-release]
AID - 2772464 [pii]
AID - TVST-20-3207 [pii]
AID - 10.1167/tvst.10.4.6 [doi]
PST - ppublish
SO  - Transl Vis Sci Technol. 2021 Apr 1;10(4):6. doi: 10.1167/tvst.10.4.6.