Endogenous bioactive lipids and the regulation of conventional outflow facility

Abstract

SummaryPerturbation of paracrine signaling within the human conventional outflow pathway influences tissue homeostasis and outflow function. For example, exogenous introduction of the bioactive lipids, sphingosine-1-phosphate, anandamide or prostaglandin F 2α , to conventional outflow tissues alters the rate of drainage of aqueous humor through the trabecular meshwork, and into Schlemm's canal. This review summarizes recent data that characterizes endogenous bioactive lipids, their receptors and associated signaling partners in the conventional outflow tract. We also discuss the potential of targeting such signaling pathways as a strategy for the development of therapeutics to treat ocular hypertension and glaucoma.

Bioactive Lysophospholipids: Role in Regulation of Aqueous Humor Outflow and Intraocular Pressure in the Context of Pathobiology and Therapy of Glaucoma

“…110 Currently, however, only little is known about the role played by PLA2s in AH outflow and IOP despite the known critical and predominant role of this class of enzymes in producing the eicosanoids and lysophospholipids that are confirmed to modulate AH outflow and IOP. 111 Very recently, we not only confirmed the distribution pattern of 2 isoforms of calcium-independent phospholipaseA2 (iPLA2b and iPLA2g) in human TM and cultured TM cells, but also established their role in regulation of AH outflow facility. 81 Using isoform-specific small molecular inhibitors of iPLA2 (S-Bromoenol lactone) and (R-Bromoenol lactone), it has been demonstrated that iPLA2g plays a significant role in the regulation of TM cell contractile properties, cell shape, and cell adhesive interactions by controlling MLC phosphorylation.…”

A Comparison of Trabecular Meshwork Sphingolipids and Ceramides of Ocular Normotensive and Hypertensive States of DBA/2J Mice

“…They have also been proposed to be potential endogenous bioactive lipids in the regulation of conventional outflow facility. 6 Sphingolipids are also known as regulators of cell proliferation, differentiation, autophagy, cellular interactions, migration, signaling, and cell death. 28 Mammalian sphingolipids are Error in Da has been provided from theoretical data.…”

“…Lipids have been found to regulate aqueous humor outflow in the eye. 6,7 Currently, the most used, but not always effective drugs approved to control outflow, are prostaglandin F 2a lipid analogs, discovered originally in 1955 from the iris, 8 they reduce IOP by directing aqueous humor drainage primarily through the uveoscleral outflow pathway. 9 Conceivably, the TM undergoes changes during aging and potentially under elevated IOP, which has not been fully understood.…”

Intraocular Pressure–Lowering Activity of NCX 470, a Novel Nitric Oxide–Donating Bimatoprost in Preclinical Models

“…1 The trabecular outflow pathway drains 60% to 90% of the AH under physiologic conditions while the remainder of AH exits via the uveoscleral drainage pathway, with its relative contribution increasing in conditions of sustained IOP elevation. 1,2 Prostaglandin F2alpha (PGF2a) analogues are the most widely prescribed IOP-lowering drugs, mainly acting by increasing uveoscleral outflow. 3 They include latanoprost, travoprost, tafluprost, and bimatoprost, with the latter being the least potent in vivo but among the most effective of the PGF2a analogues.…”