Integrins in Trabecular Meshwork and Optic Nerve Head: Possible Association with the Pathogenesis of Glaucoma

Yisheng Zhong,Xunda Luo,Jing Wang

doi:10.1155/2013/202905

Abstract

Integrins are a family of membrane-spanning proteins that are important receptors for cell adhesion to extracellular matrix proteins. They also provide connections between the extracellular environment and intracellular cytoskeletons and are responsible for activation of many intracellular signaling pathways. In vitro and in vivo data strongly indicate that integrin-mediated signaling events can modulate the organization of the actin cytoskeleton in trabecular meshwork (TM) cells and are associated with astrocyte migration and microglia activation of the optic nerve head in patients with primary open angle glaucoma. Consequently, increase in resistance in the TM outflow pathways and remodeling of the optic nerve head occur, which in turn increases intraocular pressure (IOP), adds additional mechanical stress and strain to optic nerve axons, and accelerates damage of axons initially caused by optic nerve head remodeling. Integrins appear to be ideal candidates for translating physical stress and strain into cellular responses known to occur in glaucomatous optic neuropathy.

Highlights

Glaucoma is the second leading cause of blindness worldwide
If intraocular pressure (IOP) is beyond the tolerable range of the optic nerve, retinal ganglion cells (RGCs) axons degenerate at the optic nerve head in the region of the lamina cribrosa, a process that occurs in parallel to the apoptotic death of retinal ganglion cells (RGCs)
Cross-linked actin networks (CLANs) formation could impact other actin-mediated biological processes of the trabecular meshwork (TM) that are required for normal outflow facility such as attachment to the extracellular matrix (ECM), phagocytosis, and gene expression [68,69,70], which suggests that these actin structures could possibly be involved in pathogenesis of steroid-induced glaucoma and other forms of primary open angle glaucoma (POAG) [62, 63, 68, 70]

Summary

Introduction

Glaucoma is the second leading cause of blindness worldwide. It is estimated that there are 60.5 million people with glaucoma worldwide in 2010 and will increase to 79.6 million by 2020 [1]. The ECM hypothesis is supported by the observation that perfusion of anterior eye segments in organ cultures with metalloproteinases that digest ECM components leads to a reversible increase in outflow facility [27]. Another hypothesis is based on the discovery that the cells of TM have contractile properties [28] and that an increase in TM tone increases outflow resistance [29]. Research efforts have been put in the last decade to elucidate cells response and ECM remodeling process in the TM and the optic nerve head in glaucoma, and integrins have been identified as very important participants in this process. The purpose of this paper is to summarize findings on integrins in pathogenesis of glaucoma

The Integrins and Their Ligands

Integrins in TM

Integrins in Schlemm’s Canal

Integrins in the Optic Nerve Head

Concluding Remarks