The Biology, Pathology and Therapeutic Use of Prostaglandins in the Eye

Carol B Toris; Vikas Gulati

Disclosures

Clin Lipidology. 2011;6(5):577-591. 

In This Article

Abstract and Introduction

Abstract

Prostaglandins (PGs) are ubiquitous compounds found throughout the body, including the eye. They are involved in a variety of ocular functions, two of which are intraocular pressure (IOP) regulation and mediation of inflammation. Currently, PG analogs are the mainstay of topical IOP lowering therapy for glaucoma. The IOP effects of PGs are mediated by their actions on matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases, thereby facilitating the outflow of aqueous humor from the eye. Clinically used PGs are PGF analogs which bind to PGF receptors to influence matrix metalloproteinase transcription through c-Fos and c-Jun. Biological antagonists of endogenous PGs, including steroids and nonsteroidal anti-inflammatory drugs, are commonly used for control of ocular inflammation and management of cystoid macular edema. Recent work has demonstrated that endogenous PGs are implicated in the pathogenesis of diabetic retinopathy, macular degeneration and carcinogenesis.

Introduction

Prostaglandins (PGs) were initially extracted from seminal fluid in the 1930s and then recovered from ocular tissue in 1955. A biologically active substance from rabbit irides was isolated[1] that contracted the bovine iris sphincter muscle in vitro and induced miosis when injected into the anterior chamber of cats.[2] This substance was originally given the name 'irin'. The substance later was shown to contain many PGs, along with other biologically active material.[3,4] Synthetic PGs became readily available at the end of the 1960s, making it possible to meticulously investigate PGs in ocular health and disease. Initial studies demonstrated that high concentrations of PGs injected into the anterior chamber of rabbit eyes caused a breakdown of the blood–aqueous barrier, iridial hyperemia and elevation in intraocular pressure (IOP).[5–7] By the 1970s, several ocular tissues were found to produce PGs from endogenous membrane phospholipids or from exogenous arachidonic acid.[8,9] By the late 1980s, arachidonic acid was found to produce other potent inflammatory mediators such as prostacyclin, thromboxane (TX), leukotriene and platelet activating factor. All of these studies provided support that PGs are important components in the process of ocular inflammation.[10–13]

In the late 1970s, IOP was noted often to be reduced in inflamed eyes, leading to the hypothesis that the IOP reduction is caused by endogenous PGs.[4,14] As a result, topical dosing of exogenous PGs was proposed as a new means of treating elevated IOP. Successful separation of the inflammatory component from the IOP lowering effect has made topical PGs the most efficacious and widely prescribed class of glaucoma medication to date.

This article will describe the location and function of endogenous PGs in the eye and the development and use of PG agonists for the treatment of elevated IOP, as well as the development of functional PG antagonists for the treatment of inflammation.

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