Towards axonal regeneration and neuroprotection in glaucoma: Rho kinase inhibitors as promising therapeutics. (August 2015)

• Record Type: Journal Article
• Authors: Van de Velde, Sarah; De Groef, Lies; Stalmans, Ingeborg; Moons, Lieve; Van Hove, Inge
• Is Part Of: Progress in neurobiology. Volume 131(2015:Aug.)
• Page Start: 105
• Page End: 119
• Publication Date: 2015-08
• Subjects: ROCK inhibition -- Glaucoma -- Axonal regeneration -- Neuroprotection and ocular blood flow; AAV adeno-associated viral -- AH aqueous humor -- ALS amyotrophic lateral sclerosis -- Cdk5 cyclin dependent kinase 5 -- CNTF ciliary neurotrophic factor -- CRMP-2 collapsin response mediator protein-2 -- CSPGs chondroitin sulfate proteoglycans -- Dpi day post injection -- ECM extracellular matrix -- ERM ezrin/radixin/moesin -- GAP growth associated protein -- GFAP Glial fibrillary acidic protein -- IOP intraocular pressure -- IPL inner plexiform layer -- MAG myelin-associated glycoprotein -- MAPs microtubule-associated proteins -- MLC myosin light chain -- MS multiple sclerosis -- NMDA N-mehtyl-d-aspartate -- NTG normal tension glaucoma -- OMgp oligodendorcyte myelin glycoprotein -- ONC optic nerve crush -- ONH optic nerve head -- pSTAT3 phosphorylated STAT3 -- PTEN phosphatase tensin homolog -- RGCs retinal ganglion cells -- Rho associated coiled-coil protein kinase ROCK -- TM trabecular meshwork; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2015.06.002
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: Glaucoma is a neurodegenerative disease and the second cause of blindness worldwide. Intraocular pressure (IOP) reduction is the only treatment modality available. No neuroprotective treatment is available for glaucoma treatment. Development of a neuroprotective strategy may provide improved therapeutic options. ROCK inhibitors may be a novel approach for glaucoma treatment. Abstract: Due to a prolonged life expectancy worldwide, the incidence of age-related neurodegenerative disorders such as glaucoma is increasing. Glaucoma is the second cause of blindness, resulting from a slow and progressive loss of retinal ganglion cells (RGCs) and their axons. Up to now, intraocular pressure (IOP) reduction is the only treatment modality by which ophthalmologists attempt to control disease progression. However, not all patients benefit from this therapy, and the pathophysiology of glaucoma is not always associated with an elevated IOP. These limitations, together with the multifactorial etiology of glaucoma, urge the pressing medical need for novel and alternative treatment strategies. Such new therapies should focus on preventing or retarding RGC death, but also on repair of injured axons, to ultimately preserve or improve structural and functional connectivity. In this respect, Rho-associated coiled-coil forming protein kinase (ROCK) inhibitors hold a promising potential to become very prominent drugs for future glaucoma treatment. Their field of action in the eye does not seem to be restricted to IOP reduction by targeting the trabecular meshwork or improving filtration surgery outcome. Indeed, over the past years, important progress has been made in elucidating their ability to improve ocular blood flow, to prevent RGC death/increase RGC survival and to retard axonal degeneration or induce proper axonal regeneration. Within this review, we aim to highlight the currently known capacity of ROCK inhibition to promote neuroprotection and regeneration in several in vitro, ex vivo and in vivo experimental glaucoma models.