Differential Effects of Prostaglandin E₂-Sensitive Receptors on Contractility of Human Ocular Cells That Regulate Conventional Outflow

Abstract

Cell impedance positively correlates with cellular stiffness/contractility. Because EP2/4 receptors caused decreased cell stiffness in SC, but not in TM cells, both receptors appear to mediate IOP lowering via changes in SC cell stiffness in the conventional outflow pathway.

Activation of Prostaglandin FP and EP2 Receptors Differently Modulates Myofibroblast Transition in a Model of Adult Primary Human Trabecular Meshwork Cells

“…[31][32][33][34][35] Furthermore, EP2 receptor mediates Schlemm's canal endothelial cell relaxation 36 and has been shown to regulate the mechanisms of contractility and relaxation in the TM. 35,36 F prostanoid receptor has also been implicated in the development of pulmonary 37 and myocardial fibrosis, 38 while loss of EP2 receptor exacerbates lung fibrotic lesions. 39 This dichotomy of action between FP and EP2 receptors may thus potentially lead to different outcomes on the TM alterations observed in POAG.…”

Multitargeting of selected prostanoid receptors provides agents with enhanced anti‐inflammatory activity in macrophages

“…Total RNA was isolated from human macrophages derived from CD14 + monocytes using an RNeasy Plus Mini Kit (Qiagen, Valencia, CA, USA). The procedures for 2‐step RT‐qPCR and primers for prostanoid receptors EP 1‐4 , DP 1 , FP, IP, and TP have been previously described (23). Other primers were: DP 2 forward CAA CAC CAG CAT CCG CTA CAT CGA, reverse CAC GAA GAG GAT GAC TCC ATT CTC; COX‐1: forward CAC CTT CAT CCG AGA GAT GCT CAT, reverse GCA ACT GCT TCT TCC CTT TGG TTC; COX‐2: forward CAC AGT GCA CTA CAT ACT TAC CCA C, reverse CAG CAT TGT AAG TTG GTG GAC TGT C; and glyceraldehyde 3‐phosphate dehydrogenase (GAPDH): forward GAG TCA ACG GAT TTG GTC GTA TTG, reverse CAT GTA AAC CAT GTA GTT GAG GTC.…”

Biomechanics of Schlemm's canal endothelium and intraocular pressure reduction

“…Because of the significant clinical benefit, development of such drugs is important (Heijl et al, 2002; Kopczynski and Epstein, 2014). The finding that the stiffness of SC cells is closely linked to outflow resistance (Zhou et al, 2012), and that SC cell stiffness can be specifically targeted (Wang et al, 2013; Zhou et al, 2013), suggests that agents can be identified to achieve this goal.…”

“…In separate studies, using a technique called cell dielectric spectroscopy, which measures cell impedance (an indirect indicator of cell relaxation state in the context of responses from controls, thrombin and Y27632), it was observed that the prostaglandin EP4 receptor selective agonist L-902688 had opposite effects on TM versus SC cells, decreasing impedance in TM cells while increasing it in SC cells (Wang et al, 2013). Importantly, selective activation of EP4 receptors decreases outflow resistance in live monkeys plus in enucleated mouse and human eyes, consistent with the relaxation response of SC cells and a critical role for SC in regulating outflow resistance (Boussommier-Calleja et al, 2012; Millard et al, 2011; Woodward et al, 2009).…”