%0 Journal Article
%T Lgr4 in Ocular Development and Glaucoma
%A Stefan Siwko
%A Li Lai
%A Jinsheng Weng
%A Mingyao Liu
%J Journal of Ophthalmology
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/987494
%X The leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4, also called GPR48) plays a key role in multiple developmental processes, and mice lacking Lgr4 display anterior segment dysgenesis leading to early-onset glaucomatous retinal ganglion cell loss as well as defective eyelid formation. This paper will review Lgr4 signaling and its regulation of the Axenfeld-Rieger syndrome gene Pitx2, a crucial developmental transcription factor. In addition, Wnt signaling plays an important role in eye development, with Norrin functioning to activate the Wnt receptor Frizzled 4 required for proper retinal vascularization. Recent discoveries identifying Lgr4 as a receptor for Norrin highlight the potential for Lgr4 function in retinal vascularization. Finally, several unanswered questions impeding a full understanding of Lgr4 in glaucoma are considered as avenues for further research. 1. Introduction Glaucoma is the second leading cause of blindness worldwide, but its etiology is complex and only partially understood. Frequently associated with elevated intraocular pressure (IOP) leading to a stereotypical pattern of retinal ganglion loss and cup excavation, glaucoma may result from closure of the iridocorneal angle, blockage of the trabecular meshwork responsible for aqueous humor outflow, pupil block of the space between the lens and iris necessary for humor circulation between the anterior and posterior chambers, and several other causes. Loss of the leucine-rich repeat domain-containing G protein-coupled receptor 4 (Lgr4, also called Gpr48) has been implicated in anterior segment dysgenesis including iridocorneal attachment and elevated intraocular pressure leading to early onset retinal ganglion cell loss in mice that is similar to glaucomatous damage in humans [1]. Recently published work identifies Lgr4 as a receptor for Norrin, a secreted protein with established roles in retinal neuron protection and retinal vascularization and therefore suggests an additional mechanism by which Lgr4 functions to prevent glaucoma [2]. This paper will provide an overview of Lgr4 signal transduction and its role in a wide variety of developmental processes, followed by a focus on recent developments in the role of Lgr4 in glaucoma. 2. Lgr4 Signaling The leucine-rich repeat domain-containing G protein-coupled receptors (LGRs) feature a large N-terminal extracellular domain containing multiple leucine-rich repeats and are subdivided into three groups. One group consists of the three glycoprotein hormone receptors: lutenizing hormone receptor, follicle-stimulating
%U http://www.hindawi.com/journals/joph/2013/987494/