scholarly journals Prostaglandin F2α agonists induced enhancement in collagen1 expression is involved in the pathogenesis of the deepening of upper eyelid sulcus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaku Itoh ◽  
Yosuke Ida ◽  
Hiroshi Ohguro ◽  
Fumihito Hikage

AbstractPrevious our study reported that three-dimension (3D) cultures of human orbital fibroblasts (HOFs) replicated the etiology of deepening of the upper eyelid sulcus (DUES) caused by prostaglandin F2α analogues (PGF2α-ags). To examine this further, the effects of PGF2α-ags on HOFs were characterized by (1) lipid staining (2D; two-dimension, 3D), (2) comparison of the 3D organoid sizes of preadipocytes (DIF−) or adipocytes (DIF+) that had been treated with various concentrations of several PGF2α-ags, (3) physical stiffness (3D), and (4) the mRNA expression of adipogenic related genes, extracellular matrix (ECM), tissue inhibitors of metalloproteinases (TIMPs) and matrix metalloproteinases (MMPs) (3D). PGF2α-ags caused a dramatic down-sizing of the 3D DIF+ organoids and this reduction was concentration dependent. The effects caused by PGF2α-ags were also observed in 3D preadipocytes. Micro-squeezer analysis clearly indicated that PGF2α-ags induced an increase in their physical solidity. The size of each organoid under several conditions was inversely correlated with the mRNA expression profile of collagen1 (COL1), TIMP2, and MMP2 and 9. These findings indicate that PGF2α-ags affect the expression of COL1, TIMP2, and MMP2 and 9 which, in turn, modulate the 3D ECM network within the organoids, thus resulting in their downsizing.

2012 ◽  
Vol 508 (1) ◽  
pp. 4-8 ◽  
Author(s):  
Filippo Martinelli-Boneschi ◽  
Chiara Fenoglio ◽  
Paola Brambilla ◽  
Melissa Sorosina ◽  
Giacomo Giacalone ◽  
...  

BMC Genomics ◽  
2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Tainã Figueiredo Cardoso ◽  
Raquel Quintanilla ◽  
Joan Tibau ◽  
Marta Gil ◽  
Emilio Mármol-Sánchez ◽  
...  

Author(s):  
Stephanie A. Pumphrey ◽  
Emily Zitek-Morrison ◽  
Stefano Pizzirani ◽  
Dawn M. Meola

Abstract OBJECTIVE To compare concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in aqueous humor from ophthalmologically normal dogs and dogs with naturally occurring primary angle-closure glaucoma (cPACG). SAMPLE Aqueous humor samples from 12 eyes with cPACG and 18 ophthalmologically normal eyes of dogs. PROCEDURES A multiplex fluorescence-based ELISA was used to measure concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, TIMP-2, and TIMP-4. Results for eyes with versus without cPACG were compared. RESULTS Significantly higher mean concentrations of MMP-1 (45% higher), MMP-2 (55% higher), MMP-3 (39% higher), MMP-8 (79% higher), MMP-9 (29% higher), MMP-10 (60% higher), TIMP-1 (63% higher), and TIMP-2 (136% higher) were detected in aqueous humor from eyes with cPACG, compared with ophthalmologically normal eyes. CLINICAL RELEVANCE MMPs and TIMPs have pivotal roles in extracellular matrix turnover and homeostasis in the outflow pathways of the eye. Results of the present study documented higher concentrations of MMPs and TIMPs in aqueous humor samples from dog eyes with late-stage cPACG. Although, to our knowledge, TIMPs have not previously been evaluated in the context of cPACG, the markedly higher concentration of TIMPs in eyes with cPACG suggested that inhibition of proteolysis and extracellular matrix turnover might be a factor in the development of glaucoma in susceptible individuals. However, because the present study used samples from dogs with late-stage cPACG, further work is required to characterize the temporal relationship between MMP and TIMP concentration changes and onset or progression of disease.


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