%0 Journal Article
%T New Therapeutic Targets for Intraocular Pressure Lowering
%A A. Rocha-Sousa
%A J. Rodrigues-Ara¨²jo
%A Petra Gouveia
%A Jo£¿o Barbosa-Breda
%A S. Azevedo-Pinto
%A P. Pereira-Silva
%A A. Leite-Moreira
%J ISRN Ophthalmology
%D 2013
%R 10.1155/2013/261386
%X Primary open-angle glaucoma (POAG) is a leading cause of irreversible and preventable blindness and ocular hypertension is the strongest known risk factor. With current classes of drugs, management of the disease focuses on lowering intraocular pressure (IOP). Despite of their use to modify the course of the disease, none of the current medications for POAG is able to reduce the IOP by more than 25%¨C30%. Also, some glaucoma patients show disease progression despite of the therapeutics. This paper examines the new described physiological targets for reducing the IOP. The main cause of elevated IOP in POAG is thought to be an increased outflow resistance via the pressure-dependent trabecular outflow system, so there is a crescent interest in increasing trabecular meshwork outflow by extracellular matrix remodeling and/or by modulation of contractility/TM cytoskeleton disruption. Modulation of new agents that act mainly on trabecular meshwork outflow may be the future hypotensive treatment for glaucoma patients. There are also other agents in which modulation may decrease aqueous humour production or increase uveoscleral outflow by different mechanisms from those drugs available for glaucoma treatment. Recently, a role for the ghrelin-GHSR system in the pathophysiology modulation of the anterior segment, particularly regarding glaucoma, has been proposed. 1. Introduction Glaucoma is a progressive optic neuropathy caused by death of the retinal ganglion cells (RGCs) and is the leading cause of irreversible blindness worldwide. The mechanism by which this progressive RGC death occurs is not fully understood. It is clear that multiple causes may give rise to the common effect of ganglion cell death. Clinically, it is well accepted that the major risk factor for glaucoma is elevated intraocular pressure (IOP) [1, 2]. In open angle glaucoma (OAG), elevated IOP occurs from an imbalance between production and outflow of aqueous humor (AH). The mechanical theory argues the importance of direct compression of the axonal fibers and support structures of the anterior optic nerve by elevated IOP resulting in the death of the RGCs. Lowering the IOP (baroprotection) remains the only current therapeutic approach for preserving visual function in glaucoma patients. The six classes of drugs available for glaucoma treatment (miotics, beta-blockers, alfa-agonists, epinephrine derivatives, carbonic anhydrase inhibitors, and prostaglandin analogues) act by decreasing aqueous humor production and/or by improving trabecular meshwork-Schlemm¡¯s canal or uveoscleral outflow. Better
%U http://www.hindawi.com/journals/isrn.ophthalmology/2013/261386/