Imperial College London
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ProfessorDarrylOverby

Faculty of Engineering, Department of Bioengineering

Professor of Mechanobiology
 
 
 
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Contact

 

+44 (0)20 7594 6376d.overby

 
 
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Location

 

3.07Bessemer BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Bertrand:2021:10.1016/j.plefa.2020.102235,
author = {Bertrand, JA and Woodward, DF and Sherwood, JM and Spenlehauer, A and Silvestri, C and Piscitelli, F and Marzo, VD and Yamazaki, M and Sakimura, K and Inoue, Y and Watanabe, K and Overby, DR},
doi = {10.1016/j.plefa.2020.102235},
journal = {Prostaglandins, Leukotrienes and Essential Fatty Acids},
pages = {102235--102235},
title = {Deletion of the gene encoding prostamide/prostaglandin F synthase reveals an important role in regulating intraocular pressure},
url = {http://dx.doi.org/10.1016/j.plefa.2020.102235},
volume = {165},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide F2α and prostaglandin F2α (PGF2α.). The importance of this enzyme, relative to the aldo-keto reductase (AKR) series, in providing functional tissue prostamide F2α levels was determined by creating a line of PM/PGFS gene deleted mice. Deletion of the gene encoding PM/PGFS (Fam213b / Prxl2b) was accomplished by a two exon disruption. Prostamide F2α levels in wild type (WT) and PM/PGFS knock-out (KO) mice were determined by LC/MS/MS. Deletion of Fam213b (Prxl2b) had no observed effect on behavior, appetite, or fertility. In contrast, tonometrically measured intraocular pressure was significantly elevated by approximately 4 mmHg in PM/PGFS KO mice compared to littermate WT mice. Outflow facility was measured in enucleated mouse eyes using the iPerfusion system. No effect on pressure dependent outflow facility occurred, which is consistent with the effects of prostamide F2α and PGF2α increasing outflow through the unconventional pathway. The elevation of intraocular pressure caused by deletion of the gene encoding the PM/PGFS enzyme likely results from a diversion of the endoperoxide precursor pathway to provide increased levels of those prostanoids known to raise intraocular pressure, namely prostaglandin D2 (PGD2) and thromboxane A2 (TxA2). It follows that PM/PGFS may serve an important regulatory role in the eye by providing PGF2α and prostamide F2α to constrain the influence of those prostanoids that raise intraocular pressure.
AU  - Bertrand,JA
AU  - Woodward,DF
AU  - Sherwood,JM
AU  - Spenlehauer,A
AU  - Silvestri,C
AU  - Piscitelli,F
AU  - Marzo,VD
AU  - Yamazaki,M
AU  - Sakimura,K
AU  - Inoue,Y
AU  - Watanabe,K
AU  - Overby,DR
DO  - 10.1016/j.plefa.2020.102235
EP  - 102235
PY  - 2021///
SN  - 0952-3278
SP  - 102235
TI  - Deletion of the gene encoding prostamide/prostaglandin F synthase reveals an important role in regulating intraocular pressure
T2  - Prostaglandins, Leukotrienes and Essential Fatty Acids
UR  - http://dx.doi.org/10.1016/j.plefa.2020.102235
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33418484
UR  - https://www.sciencedirect.com/science/article/pii/S0952327820301939?via%3Dihub
UR  - http://hdl.handle.net/10044/1/86298
VL  - 165
ER  -
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