| First Author | Bertrand JA | Year | 2021 |
| Journal | Prostaglandins Leukot Essent Fatty Acids | Volume | 165 |
| Pages | 102235 | PubMed ID | 33418484 |
| Mgi Jnum | J:307536 | Mgi Id | MGI:6721176 |
| Doi | 10.1016/j.plefa.2020.102235 | Citation | Bertrand JA, et al. (2021) Deletion of the gene encoding prostamide/prostaglandin F synthase reveals an important role in regulating intraocular pressure. Prostaglandins Leukot Essent Fatty Acids 165:102235 |
| abstractText | Prostamide/prostaglandin F synthase (PM/PGFS) is an enzyme with very narrow substrate specificity and is dedicated to the biosynthesis of prostamide F2alpha and prostaglandin F2alpha (PGF2alpha.). The importance of this enzyme, relative to the aldo-keto reductase (AKR) series, in providing functional tissue prostamide F2alpha 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 F2alpha 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 F2alpha and PGF2alpha 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 PGF2alpha and prostamide F2alpha to constrain the influence of those prostanoids that raise intraocular pressure. |
