Effect of Prostaglandin E2 Agonist Omidenepag on the Expression of Matrix Metalloproteinase in Trabecular Meshwork Cells

Overview

Journal Korean J Ophthalmol

Specialty Ophthalmology

Date 2022 Jan 24

PMID 35067026

Authors

Jeong Yeub Kim

Jae Woo Kim

Affiliations

Soon will be listed here.

Abstract

Purpose: To investigate the effects of prostaglandin E2 agonist omidenepag (OMD) on the expression of matrix metalloproteinase (MMP) in human trabecular meshwork (TM) cells.

Methods: Primarily cultured human TM cells were exposed to 0, 1, 10, or 40 µmol/L OMD for 3 days. The permeability through the TM cell monolayer was assessed using carboxyfluorescein. Expressions of messenger ribonucleic acid and protein levels of MMP-1, MMP-3, and MMP-9 were measured by reverse transcription polymerase chain reaction and Western blotting, respectively. Also, the permeability, expression of messenger ribonucleic acid, and protein levels of MMPs were measured after exposure to 1 µmol/L latanoprost free acid (LAT).

Results: OMD and LAT did not affect the cellular survival (all p > 0.05). Each concentration of OMD and LAT did not affect the permeability of carboxyfluorescein significantly (all p > 0.05). LAT increased the level of MMP-1 protein but did not increase the levels of MMP-3 and MMP-9 proteins. Each concentration of OMD did not affect the levels of MMP-1, MMP-3, and MMP-9 proteins (all p > 0.05).

Conclusions: In TM cells, prostaglandin E2 agonist OMD did not increase the permeability through the TM cell monolayer, and the protein levels of MMPs. These suggest that the direct effect on the trabecular outflow by OMD may be limited.

References

Kaneko Y, Ohta M, Inoue T, Mizuno K, Isobe T, Tanabe S . Effects of K-115 (Ripasudil), a novel ROCK inhibitor, on trabecular meshwork and Schlemm's canal endothelial cells. Sci Rep. 2016; 6:19640. PMC: 4725980. DOI: 10.1038/srep19640. View

Fuwa M, Toris C, Fan S, Taniguchi T, Ichikawa M, Odani-Kawabata N . Effects of a Novel Selective EP2 Receptor Agonist, Omidenepag Isopropyl, on Aqueous Humor Dynamics in Laser-Induced Ocular Hypertensive Monkeys. J Ocul Pharmacol Ther. 2018; 34(7):531-537. DOI: 10.1089/jop.2017.0146. View

Woodward D, Wang J, Stamer W, Lutjen-Drecoll E, Krauss A, Toris C . Antiglaucoma EP Agonists: A Long Road That Led Somewhere. J Ocul Pharmacol Ther. 2019; 35(9):469-474. DOI: 10.1089/jop.2019.0041. View

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

Keller K, Aga M, Bradley J, Kelley M, Acott T . Extracellular matrix turnover and outflow resistance. Exp Eye Res. 2008; 88(4):676-82. PMC: 2700052. DOI: 10.1016/j.exer.2008.11.023. View

El-Shabrawi Y, Eckhardt M, Berghold A, Faulborn J, Auboeck L, Mangge H . Synthesis pattern of matrix metalloproteinases (MMPs) and inhibitors (TIMPs) in human explant organ cultures after treatment with latanoprost and dexamethasone. Eye (Lond). 2000; 14 ( Pt 3A):375-83. DOI: 10.1038/eye.2000.92. View

Vranka J, Kelley M, Acott T, Keller K . Extracellular matrix in the trabecular meshwork: intraocular pressure regulation and dysregulation in glaucoma. Exp Eye Res. 2015; 133:112-25. PMC: 4379427. DOI: 10.1016/j.exer.2014.07.014. View

Ida Y, Hikage F, Umetsu A, Ida H, Ohguro H . Omidenepag, a non-prostanoid EP2 receptor agonist, induces enlargement of the 3D organoid of 3T3-L1 cells. Sci Rep. 2020; 10(1):16018. PMC: 7524797. DOI: 10.1038/s41598-020-72538-x. View

Aihara M, Lu F, Kawata H, Tanaka Y, Yamamura K, Odani-Kawabata N . Pharmacokinetics, Safety, and Intraocular Pressure-Lowering Profile of Omidenepag Isopropyl, a Selective, Nonprostaglandin, Prostanoid EP2 Receptor Agonist, in Healthy Japanese and Caucasian Volunteers (Phase I Study). J Ocul Pharmacol Ther. 2019; 35(10):542-550. PMC: 6918846. DOI: 10.1089/jop.2019.0044. View

10.

Oh D, Martin J, Williams A, Russell P, Birk D, Rhee D . Effect of latanoprost on the expression of matrix metalloproteinases and their tissue inhibitors in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2006; 47(9):3887-95. DOI: 10.1167/iovs.06-0036. View

11.

Hinz B, Rosch S, Ramer R, Tamm E, Brune K . Latanoprost induces matrix metalloproteinase-1 expression in human nonpigmented ciliary epithelial cells through a cyclooxygenase-2-dependent mechanism. FASEB J. 2005; 19(13):1929-31. DOI: 10.1096/fj.04-3626fje. View

12.

Biswas S, Bhattacherjee P, Paterson C . Prostaglandin E2 receptor subtypes, EP1, EP2, EP3 and EP4 in human and mouse ocular tissues--a comparative immunohistochemical study. Prostaglandins Leukot Essent Fatty Acids. 2004; 71(5):277-88. DOI: 10.1016/j.plefa.2004.03.021. View

13.

Wang J, Woodward D, Stamer W . Differential effects of prostaglandin E2-sensitive receptors on contractility of human ocular cells that regulate conventional outflow. Invest Ophthalmol Vis Sci. 2013; 54(7):4782-90. PMC: 3719448. DOI: 10.1167/iovs.13-12363. View

14.

Pang I, Hellberg P, Fleenor D, Jacobson N, Clark A . Expression of matrix metalloproteinases and their inhibitors in human trabecular meshwork cells. Invest Ophthalmol Vis Sci. 2003; 44(8):3485-93. DOI: 10.1167/iovs.02-0756. View

15.

Quigley H . Glaucoma. Lancet. 2011; 377(9774):1367-77. DOI: 10.1016/S0140-6736(10)61423-7. View

16.

Yamamoto Y, Taniguchi T, Inazumi T, Iwamura R, Yoneda K, Odani-Kawabata N . Effects of the Selective EP2 Receptor Agonist Omidenepag on Adipocyte Differentiation in 3T3-L1 Cells. J Ocul Pharmacol Ther. 2020; 36(3):162-169. PMC: 7175626. DOI: 10.1089/jop.2019.0079. View

17.

Winkler N, Fautsch M . Effects of prostaglandin analogues on aqueous humor outflow pathways. J Ocul Pharmacol Ther. 2013; 30(2-3):102-9. PMC: 3991965. DOI: 10.1089/jop.2013.0179. View

18.

Flach A, Eliason J . Topical prostaglandin E2 effects on normal human intraocular pressure. J Ocul Pharmacol. 1988; 4(1):13-8. DOI: 10.1089/jop.1988.4.13. View

19.

Alexander J, Samples J, Van Buskirk E, Acott T . Expression of matrix metalloproteinases and inhibitor by human trabecular meshwork. Invest Ophthalmol Vis Sci. 1991; 32(1):172-80. View

20.

Schlotzer-Schrehardt U, Zenkel M, Nusing R . Expression and localization of FP and EP prostanoid receptor subtypes in human ocular tissues. Invest Ophthalmol Vis Sci. 2002; 43(5):1475-87. View